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- ACRONYMS AND DEFINITIONS
- AAP - American Academy of Pediatrics
- ADHD - Attention-deficit/hyperactivity disorder
- CNS - Central nervous system
- CV - Cardiovascular
- DSM - Diagnostic and Statistical Manual of Mental Disorders
- NICE - National Institute for Health and Care Excellence
- AMPHETAMINES
Adderall® | Adderall XR® (amphetamine salts)
Dosage forms
Tablet (Adderall®)
- 5 mg
- 7.5 mg
- 10 mg
- 12.5 mg
- 15 mg
- 20 mg
- 30 mg
Capsule, extended-release (Adderall XR®)
- 5 mg
- 10 mg
- 15 mg
- 20 mg
- 25 mg
- 30 mg
Adderall contains 4 amphetamine salts in equal parts:
- Dextroamphetamine saccharate
- Amphetamine aspartate
- Dextroamphetamine sulfate
- Amphetamine sulfate
Dosing - Adderall®
ADHD
- Children 3 - 5 years old
- Starting: 2.5 mg once daily
- Increase daily dose in increments of 2.5 mg at weekly intervals
- Children ≥ 6 years old
- Starting: 5 mg once or twice daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Doses > 40 mg a day are rare
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Narcolepsy
- Children 6 - 12 years old
- Starting: 5 mg once daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Children ≥ 12 years old
- Starting: 10 mg daily
- Increase daily dose in increments of 10 mg at weekly intervals
- Usual dose 5 - 60 mg/day
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Dosing - Adderall XR®
ADHD
- Children 6 - 12 years old
- Starting: 10 mg once daily
- Maximum: 30 mg once daily
- Increase dose in increments of 5 - 10 mg at weekly intervals
- Children 13 - 17 years old
- Starting: 10 mg once daily
- Increase dose in increments of 10 mg at weekly intervals
- In trials, doses up to 40 mg/day were used
- Adults
- Starting: 20 mg once daily
- Increase dose in increments of 10 mg at weekly intervals
- In trials, doses up to 60 mg/day were used
Generic / Price
- Adderall® tablet - YES/$ (60 tablets)
- Adderall XR® - YES/$ (30 capsules )
Other
Adderall®
- Tablets are scored and may be broken in two
- May take without regard to food
Adderall XR®
- May take without regard to food
- Doses should be given in the morning to prevent insomnia
- When switching from Adderall, give same total daily dose as once daily Adderall XR
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
Pharmacokinetics
Adderall®
- Half-life:
- d isomer ∼ 10 hours
- l isomer ∼ 13 hours
- Time to max level: 3 hours
Adderall XR®
- Half-life:
- d isomer ∼ 10 hours
- l isomer ∼ 13 hours
- Time to max level: 7 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
Adderall
- ADHD
- Narcolepsy
Adderall XR
- ADHD
Side effects
- NOTE: Information from Adderall XR PI. Only side effects that occurred at an incidence of ≥ 3% and ≥ 3% more than placebo are listed.
Children 6 - 12 years old | ||
---|---|---|
Side effect | Adderall XR | Placebo |
Loss of appetite | 22% | 2% |
Insomnia | 17% | 2% |
Upset stomach | 14% | 10% |
Emotional lability | 9% | 2% |
Vomiting | 7% | 4% |
Nervousness | 6% | 2% |
Fever | 5% | 2% |
Weight loss* | 4% | 0% |
Adults | ||
---|---|---|
Side effect | Adderall XR | Placebo |
Dry mouth | 35% | 5% |
Loss of appetite | 33% | 3% |
Insomnia | 27% | 13% |
Headache | 26% | 13% |
Weight loss | 10% | 0% |
Nausea | 8% | 3% |
Agitation | 8% | 5% |
Anxiety | 8% | 5% |
Dizziness | 7% | 0% |
Diarrhea | 6% | 0% |
Tachycardia | 6% | 3% |
Urinary tract infection | 5% | 0% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Adzenys XR-ODT™ | Adzenys ER™ (amphetamine base)
Dosage forms
Orally disintegrating tablet (Adzenys XR-ODT™)
- 3.1 mg
- 6.3 mg
- 9.4 mg
- 12.5 mg
- 15.7 mg
- 18.8 mg
Suspension (Adzenys ER™)
- 1.25 mg/ml
- Comes in 450 ml bottle
- Adzenys contains 50% immediate-release and 50% delayed-release amphetamine in a 3:1 ratio of d- to l-amphetamine
Dosing
ADHD
- 6 - 12 years old
- Starting: 6.3 mg once daily in the morning
- Maximum: 18.8 mg once daily
- Increase dose in increments of 3.1 or 6.3 mg per day at weekly intervals
- 13 - 17 years old
- Starting: 6.3 mg once daily in the morning
- Maximum: 12.5 mg once daily
- Increase dose in increments of 3.1 or 6.3 mg per day at weekly intervals
- Adults
- Recommended dose: 12.5 mg once daily
Switching from Adderall XR
Adderall XR dose | Adzenys dose |
---|---|
5 mg | 3.1 mg |
10 mg | 6.3 mg |
15 mg | 9.4 mg |
20 mg | 12.5 mg |
25 mg | 15.7 mg |
30 mg | 18.8 mg |
Generic / Price
- Adzenys XR-ODT - NO/$$$$
- Adzenys ER - NO/$$$$
Other
Orally disintegrating tablet
- Tablet is placed on the tongue where it disintegrates
- Do not crush or chew tablet
- May take without regard to food
- Leave tablet in blister pack until ready to take
Suspension
- May take without regard to food
- Shake bottle before administering
- Do not add to food or mix with other liquids before consuming
- Store at room temperature
Pharmacokinetics
Orally disintegrating tablet
- Half-life (6 - 12 years):
- d-isomer ∼ 9 - 10 hours
- l-isomer ∼ 10 - 11 hours
- Half-life (adults):
- d-isomer ∼ 11 hours
- l-isomer ∼ 14 hours
- Time to max level: 5 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indication
- ADHDSide effects
- NOTE: Only side effects that occurred at an overall incidence ≥ 5% and more than placebo are listed
Children 6 - 12 years | ||
---|---|---|
Side effect | Adzenys | Placebo |
Loss of appetite | 22% | 2% |
Insomnia | 17% | 2% |
Abdominal pain | 14% | 10% |
Emotional lability | 9% | 2% |
Vomiting | 7% | 4% |
Nervousness | 6% | 2% |
Nausea | 5% | 3% |
Fever | 5% | 2% |
Adults | ||
---|---|---|
Side effect | Adzenys | Placebo |
Dry mouth | 35% | 5% |
Loss of appetite | 33% | 3% |
Insomnia | 27% | 13% |
Headache | 26% | 13% |
Weight loss | 10% | 0% |
Nausea | 8% | 3% |
Agitation | 8% | 5% |
Anxiety | 8% | 5% |
Dizziness | 7% | 0% |
Diarrhea | 6% | 0% |
Tachycardia | 6% | 3% |
Asthenia | 6% | 5% |
Urinary tract infection | 5% | 0% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacid, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - amphetamines may counteract the effects of alpha blockers
- Beta blockers - amphetamines may counteract the effects of beta blockers
- Blood pressure medications - amphetamines may raise blood pressure and counteract the effects of blood pressure medications
- Tricyclic antidepressants (TCAs) - amphetamines may potentiate the effects of TCAs and vice versa
- Meperidine - amphetamines may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of amphetamines
- Lithium - lithium may block the effects of amphetamines
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Desoxyn® (methamphetamine hydrochloride)
Dosage forms
Tablet
- 5 mg
Dosing
ADHD ( ≥ 6 years old)
- Starting: 5 mg once or twice daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Usual effective dose is 20 - 25 mg daily
- Total daily dose may be given once daily or divided into two doses
- May take without regard to food
Obesity ( ≥ 12 years old and adults)
- Starting: 5 mg one-half hour before meals
- Treatment should not exceed a few weeks
Generic / Price
- YES/$$$$ (#60)Pharmacokinetics
- Half-life: 4 - 5 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
- In weight loss, amphetamines are thought to suppress appetite
FDA-approved indications
- ADHD
- Obesity
Side effects
- The incidence of side effects with Desoxyn are not well-defined
- Desoxyn is metabolized to amphetamine. Amphetamine is a component of Adderall. Side effects of Desoxyn would be expected to be similar to Adderall but may not be exactly the same. See Adderall side effects above for more.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Dexedrine® | Dexedrine spansule® | Zenzedi® (dextroamphetamine sulfate)
Dosage forms
Tablet (Dexedrine®)
- 5 mg
- 10 mg
Solution (Dexedrine®)
- 5 mg/5 ml (1 mg/ml)
Capsule, extended-release (Dexedrine spansule®)
- 5 mg
- 10 mg
- 15 mg
Tablet (Zenzedi®)
- 2.5 mg
- 5 mg
- 7.5 mg
- 10 mg
- 15 mg
- 20 mg
- 30 mg
Dosing - Dexedrine® | Zenzedi®
ADHD
- Children 3 - 5 years old
- Starting: 2.5 mg once daily
- Increase daily dose in increments of 2.5 mg at weekly intervals
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
- Children ≥ 6 years old
- Starting: 5 mg once or twice daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Doses > 40 mg a day are rare
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Narcolepsy
- Children 6 - 12 years old
- Starting: 5 mg once daily
- Maintenance: 5 - 60 mg/day given in divided doses
- Increase daily dose in increments of 5 mg at weekly intervals
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
- Children ≥ 12 years old
- Starting: 10 mg once daily
- Maintenance: 5 - 60 mg/day given in divided doses
- Increase daily dose in increments of 10 mg at weekly intervals
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Dosing - Dexedrine spansule®
ADHD
- Children ≥ 6 years old
- Starting: 5 mg once or twice daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Doses > 40 mg/day are rarely needed
Narcolepsy
- Children 6 - 12 years old
- Starting: 5 mg once daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Children ≥ 12 years old
- Starting: 10 mg once daily
- Increase daily dose in increments of 10 mg at weekly intervals
- Usual dose 5 - 60 mg/day
Generic / Price
- Dexedrine® tablet (#60) - YES/$
- Dexedrine spansule® (#30) - YES/$$
- Dexedrine solution (150 ml) - YES/$$
- Zenzedi tablet (#60) - 5 and 10 mg - YES/$ | Other doses - NO/$$$$
Other
Dexedrine®, Zenzedi®
- May take without regard to food
- Dexedrine tablets are scored so that they may be halved
Dexedrine spansule®
- Swallow capsules whole
- May take without regard to food
Pharmacokinetics
Dexedrine®
- Time to max level: 3 hours
- Half-life: 12 hours
Dexedrine spansule®
- Time to max level: 8 hours
- Half-life: 12 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHD
- Narcolepsy
Side effects
- The incidence of side effects with Dexedrine are not well-defined
- Dextroamphetamine sulphate is a component of Adderall. Side effects of Dexedrine would be expected to be similar to Adderall but may not be exactly the same. See Adderall side effects above for more.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Dyanavel XR® (amphetamine base)
Dosage forms
Tablet, extended-release
- 5 mg
- 10 mg
- 15 mg
- 20 mg
Suspension, extended-release
- 2.5 mg/ml
- Comes in 464 ml bottle
- Suspension is bubblegum flavored
- Store at room temp
- Dyanavel contains amphetamine in a 3.2:1 ratio of d- to l-amphetamine
- There are three active ingredients: amphetamine, dextroamphetamine sulfate, and amphetamine aspartate
- Dosage strengths are expressed in terms of amphetamine base
Dosing
ADHD ( ≥ 6 years old)
- Starting: 2.5 - 5 mg once daily in the morning
- Maintenance: 2.5 - 20 mg once daily in the morning
- Maximum: 20 mg once daily
- Increase dose in increments of 2.5 to 10 mg per day every 4 to 7 days
- When switching from other amphetamine products, discontinue other product and titrate Dyanavel as above
- Dyanavel is NOT equivalent to other amphetamine products on a mg-per-mg basis
- Tablets may be chewed or swallowed whole. The 5 mg tablet is scored for halving.
- May take without regard to food
Generic / Price
- Tablet and suspension: NO/$$$$
Pharmacokinetics
Half-life (adults):
- d isomer: 12 - 14 hours
- l isomer: 15 - 17 hours
- d isomer: 10.4 hours
- l isomer: 12.1 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indication
- Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older
Side effects
- The incidence of side effects with Dyanavel are not well-defined
- Dyanavel contains amphetamine base which is the same drug that is in Adzenys. Side effects of Dyanavel would be expected to be similar to Adzenys. See Adzenys side effects for more.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - amphetamines may counteract the effects of alpha blockers
- Beta blockers - amphetamines may counteract the effects of beta blockers
- Blood pressure medications - amphetamines may raise blood pressure and counteract the effects of blood pressure medications
- Tricyclic antidepressants (TCAs) - amphetamines may potentiate the effects of TCAs and vice versa
- Meperidine - amphetamines may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of amphetamines
- Lithium - lithium may block the effects of amphetamines
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Evekeo® | Evekeo ODT™ (amphetamine sulphate)
Dosage forms
Tablet (Evekeo®)
- 5 mg
- 10 mg
Orally disintegrating tablet (Evekeo ODT™)
- 5 mg
- 10 mg
- 15 mg
- 20 mg
Dosing - Evekeo®
ADHD
- Children 3 - 5 years old
- Starting: 2.5 mg once daily
- Increase daily dose in increments of 2.5 mg at weekly intervals
- Children ≥ 6 years old
- Starting: 5 mg once or twice daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Doses > 40 mg a day are rare
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Narcolepsy
- Children 6 - 12 years old
- Starting: 5 mg once daily
- Increase daily dose in increments of 5 mg at weekly intervals
- Children ≥ 12 years old
- Starting: 10 mg daily
- Increase daily dose in increments of 10 mg at weekly intervals
- Usual dose 5 - 60 mg/day
- Give first dose on awakening and additional doses at intervals of 4 - 6 hours
Obesity ( ≥ 12 years old)
- 5 - 10 mg given 30 - 60 minutes before each meal
- Usual daily dose is 30 mg
Dosing - Evekeo ODT™
ADHD (6 - 17 years old)
- Starting: 5 mg once or twice daily
- If necessary, administer an additional dose after 4 to 6 hours
- Increase daily dose in increments of 5 mg at weekly intervals
- Only in rare cases will it be necessary to exceed a total of 40 mg daily
Generic / Price
- Evekeo - YES/$$
- Evekeo ODT - NO/$$$$
Other
Evekeo
- Tablets are scored and may be broken in two
- May take without regard to food
Evekeo ODT
- May take without regard to food or liquid
- Do not remove tablet from blister pack until ready to take
- Do not cut or crush tablet
- Place tablet on tongue and allow to disintegrate without chewing or crushing
- Swallow dissolved tablet. No liquid is necessary.
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
- In weight loss, amphetamines are thought to suppress appetite
FDA-approved indications
Evekeo®
- ADHD
- Narcolepsy
- Obesity
Evekeo ODT™
- ADHD
Side effects
In one small (N=105) open-label trial, the following side effects were reported for Evekeo (10 - 40 mg/day). Strength of association is not well-defined.
- Decreased appetite - 28%
- Infections - 22%
- Abdominal pain - 15%
- Irritability - 14%
- Headache - 13%
- Insomnia - 10%
- Fatigue - 10%
- Affect lability - 9%
- Tachycardia - 9%
- Nausea - 6%
- Vomiting - 6%
- Dry mouth - 6%
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Mydayis™ (amphetamine salts)
Capsule, extended-release
- 12.5 mg
- 25 mg
- 37.5 mg
- 50 mg
Mydayis contains 4 amphetamine salts in equal parts:
- Dextroamphetamine saccharate
- Amphetamine aspartate
- Dextroamphetamine sulfate
- Amphetamine sulfate
Dosing
ADHD
- 13 - 17 years old
- Starting: 12.5 mg once daily
- Maximum: 25 mg once daily
- Increase dose in increments of 12.5 mg at no less than weekly intervals
- Administer once daily in the morning upon awakening
- 18 - 55 years
- Starting: 12.5 mg once daily
- Maximum: 50 mg once daily
- A starting dose of 25 mg may be considered for some patients
- Increase dose in increments of 12.5 mg at no less than weekly intervals
- Administer once daily in the morning upon awakening
Generic / Price
- NO/$$$$ (30 caps)Other
- Take consistently either with food or without food. High fat meal slows the rate of absorption but does not affect the extent of absorption.
- Capsules may be opened and sprinkled on applesauce. Applesauce should be swallowed immediately without chewing.
Pharmacokinetics
Half-life:
- d isomer ∼ 10 - 11 hours
- l isomer ∼ 10 - 13 hours
Mechanism of action
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 3% and twice the incidence of placebo are listed.
Adolescents | ||
---|---|---|
Side effect | Mydayis | Placebo |
Decreased appetite | 22% | 6% |
Insomnia | 8% | 3% |
Nausea | 8% | 4% |
Irritability | 6% | 3% |
Weight loss | 5% | 1% |
Dizziness | 4% | 0% |
Upper abdominal pain | 4% | 1% |
Adults | ||
---|---|---|
Side effect | Mydayis | Placebo |
Insomnia | 31% | 8% |
Decreased appetite | 30% | 4% |
Dry mouth | 23% | 4% |
Weight loss | 9% | 0% |
Heart rate increase | 9% | 0% |
Anxiety | 7% | 3% |
Palpitations | 4% | 2% |
Dysmenorrhea | 4% | 2% |
Depression | 3% | 0% |
Diarrhea | 3% | 1% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
- Phenobarbital - amphetamines may delay the absorption of phenobarbital
- Phenytoin - amphetamines may delay the absorption of phenytoin
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
- Kidney disease
- CrCl 15 to <30 ml/min
- Adults: starting dose 12.5 mg daily; maximum 25 mg daily
- Pediatric (13 - 17 years): maximum 12.5 mg daily
- CrCl < 15 ml/min: DO NOT USE
Vyvanse® (lisdexamfetamine)
Dosage forms
Capsule
- 10 mg
- 20 mg
- 30 mg
- 40 mg
- 50 mg
- 60 mg
- 70 mg
Dosing
ADHD ( ≥ 6 years old and adults)
- Starting: 30 mg once daily
- Maximum: 70 mg once daily
- Increase dose in increments of 10 - 20 mg at weekly intervals
Binge eating disorder (adults)
- Starting: 30 mg once daily
- Target: 50 - 70 mg once daily
- Maximum: 70 mg once daily
- Increase dose in increments of 20 mg at weekly intervals
Generic / Price
- NO/$$$$ (#30)Other
- May take without regard to food
- Capsules may be opened and contents mixed with yogurt, water, or orange juice. Contents should be mixed until completely dispersed. Film coating left in glass is inactive ingredients. Active component dissolves completely.
Pharmacokinetics
- Time to max level: 3.5 hours
- Lisdexamfetamine is converted to dextroamphetamine
- Half-life of dextroamphetamine is 12 hours
Mechanism of action
- Lisdexamfetamine is a prodrug of dextroamphetamine
- Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood. In binge eating disorder, stimulants suppress appetite.
FDA-approved indications
- ADHD
- Moderate to severe binge eating disorder
Side effects
- NOTE: Only side effects that occurred at an incidence of ≥ 4% and twice the incidence of placebo are listed.
Children (6 - 12 years old) | ||
---|---|---|
Side effect | Vyvanse | Placebo |
Decreased appetite | 39% | 4% |
Insomnia | 23% | 3% |
Upper abdominal pain | 12% | 6% |
Irritability | 10% | 0% |
Vomiting | 9% | 4% |
Weight loss✝ | 9% | 1% |
Nausea | 6% | 3% |
Dry mouth | 5% | 0% |
Dizziness | 5% | 0% |
Adults | ||
---|---|---|
Side effect | Vyvanse | Placebo |
Decreased appetite | 27% | 2% |
Insomnia | 27% | 8% |
Dry mouth | 26% | 3% |
Diarrhea | 7% | 0% |
Nausea | 7% | 0% |
Anxiety | 6% | 0% |
Anorexia | 5% | 0% |
Feeling jittery | 4% | 0% |
Decreased weight✝ | 3% | 0% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
- CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
- Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Lab interactions
- Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels
Contraindications / Precautions
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease
- CrCl 15 - <30 ml/min: do not exceed 50 mg/day
- CrCl < 15 ml/min: do not exceed 30 mg/day
- METHYLPHENIDATE
Adhansia XR™ (methylphenidate hydrochloride)
Dosage forms
Capsule, extended-release
- 25 mg
- 35 mg
- 45 mg
- 55 mg
- 70 mg
- 85 mg
Dosing
ADHD ( ≥ 6 years old)
- Starting: 25 mg once daily
- Maximum: Pediatric - 85 mg/day | Adults - 100 mg/day
- Increase dose in increments of 10 - 15 mg/day at intervals of no less than 5 days
- Doses above 70 mg/day in pediatric patients and 85 mg/day in adults were associated with a disproportionate increase in side effects
- Capsules may be opened and sprinkled on applesauce or yogurt. Swallow mixture whole without chewing within 10 minutes.
- May take without regard to food
Generic / Price
- NO/$$$$ (#30)Pharmacokinetics
Time to max level: bimodal
- First: 1.5 hours
- Second: 12 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 2% and more than placebo are listed
Children ( 12 - 17 years old) | ||
---|---|---|
Side effect | Adhansia 25 - 85 mg | Placebo |
Decreased appetite | 20% | 0% |
Insomnia | 6% | 1% |
Weight loss | 7% | 0% |
Upper abdominal pain | 4% | 1% |
Nausea | 6% | 4% |
Dizziness | 3% | 0% |
Dry mouth | 3% | 1% |
Vomiting | 3% | 0% |
Adults | ||
---|---|---|
Side effect | Adhansia 25 - 100 mg | Placebo |
Insomnia | 16% | 4% |
Decreased appetite | 11% | 3% |
Dry mouth | 9% | 4% |
Nausea | 6% | 3% |
Diarrhea | 4% | 1% |
Feeling jittery | 4% | 1% |
Weight loss | 4% | 1% |
Upper respiratory infection | 2% | 1% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Acid-reducing drugs (e.g. PPIs, antacids, H2 blockers) - acid-reducing drugs may alter the release and pharmacokinetics of Adhansia. Monitor for changes in clinical effect when combining.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- FD&C Yellow No. 5 - Adhansia contains FD&C Yellow No. 5 (tartrazine) which can cause allergic reactions in susceptible patients. Patients with aspirin hypersensitivity may be at increased risk.
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
- Kidney disease - has not been studied. Renal clearance is not an important route of methylphenidate clearance, so renal insufficiency is not expected to have a significant effect on methylphenidate pharmacokinetics.
Aptensio XR® (methylphenidate hydrochloride)
Dosage forms
Capsule, extended-release
- 10 mg
- 15 mg
- 20 mg
- 30 mg
- 40 mg
- 50 mg
- 60 mg
Dosing
ADHD (children ≥ 6 years old)
- Starting: 10 mg once daily
- Maximum: 60 mg once daily
- Increase daily dose in increments of 10 mg at weekly intervals
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
- May take without regard to food
Generic / Price
- NO/$$$$ (#30)Pharmacokinetics
Time to max level: bimodal
- First: 2 hours
- Second: 8 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 3% are listed
Children ( ≥ 6 years old) | ||
---|---|---|
Side effect | Aptensio XR | Placebo |
Headache | 10.9% | 8.5% |
Insomnia | 9.8% | 2.1% |
Upper abdominal pain | 8.2% | 0% |
Decreased appetite | 4.9% | 0% |
Vomiting | 3.8% | 0% |
Nausea | 3.8% | 2.1% |
Dizziness | 2.2% | 2.1% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Azstarys™ (serdexmethylphenidate and dexmethylphenidate)
Dosage forms
Capsule
- 26.1/5.2 mg
- 39.2/7.8 mg
- 52.3/10.4 mg
Dosing
ADHD (6 - 12 years old)
- Starting: 39.2/7.8 mg once daily in the morning
- Maintenance: after 1 week, increase dose to 52.3/10.4 mg, or decreased to 26.1/5.2 mg, depending on response and tolerability
- Maximum: 52.3/10.4 mg once daily in the morning
- May take without regard to food
- Capsules may be opened and the contents sprinkled into 50 mL of water or over 2 tablespoons of applesauce. Consume within 10 minutes of mixing.
- Do not substitute Azstarys for other methylphenidate products on a milligram-per-milligram basis. When switching from another methylphenidate product, discontinue that treatment, and titrate as above.
ADHD (13 - 17 years old and adults)
- Starting: 39.2/7.8 mg once daily in the morning
- Maintenance: after 1 week, increase dose to 52.3/10.4 mg
- Maximum: 52.3/10.4 mg once daily in the morning
- May take without regard to food
- Capsules may be opened and the contents sprinkled into 50 mL of water or over 2 tablespoons of applesauce. Consume within 10 minutes of mixing.
- Do not substitute Azstarys for other methylphenidate products on a milligram-per-milligram basis. When switching from another methylphenidate product, discontinue that treatment, and titrate as above.
Generic / Price
NO/$$$$Pharmacokinetics
- Time to max level: 2 hours (fasting) | 4.25 hours (with food)
- Half-life
- Serdexmethylphenidate: 5.7 hours
- Dexmethylphenidate : 11.7 hours
Mechanism of action
- Serdexmethylphenidate is a prodrug of dexmethylphenidate. Dexmethylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.
FDA-approved indications
- ADHD in adults and children ≥ 6 years oldSide effects
- NOTE: The Azstarys PI does not give specific side effect data. The information below is from the Focalin PI. Focalin has the same active ingredient (dexmethylphenidate) as Azstarys.
Children | ||
---|---|---|
Side effect | Focalin XR | Placebo |
Gastrointestinal disorders | 38% | 19% |
Decreased appetite | 30% | 9% |
Psychiatric disorders | 26% | 15% |
Headache | 25% | 11% |
Upset stomach | 8% | 4% |
Anxiety | 6% | 0% |
Adults | ||
---|---|---|
Side effect | Focalin XR 40 mg/day | Placebo |
Psychiatric disorders | 46% | 30% |
Gastrointestinal disorders | 44% | 19% |
Headache | 39% | 19% |
Dry mouth | 20% | 4% |
Anxiety | 11% | 2% |
Upset stomach | 9% | 2% |
Pharyngolaryngeal pain | 7% | 2% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Heartburn medications (antacids, PPIs, H2 antagonists, etc.) - heartburn medications may alter the absorption of methylphenidate
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - stimulants may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Bronchospasm, rash, and pruritus have been reported in patients who received Azstarys. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
- Kidney disease - has not been studied. Renal clearance is not an important route of elimination, so kidney disease is not expected to affect Azstarys pharmacokinetics. Manufacturer makes no dosage recommendation.
Concerta® (methylphenidate hydrochloride)
Dosage forms
Tablet, extended-release
- 18 mg
- 27 mg
- 36 mg
- 54 mg
Dosing
ADHD
- Children 6 - 12 years
- Starting: 18 mg once daily
- Maintenance: 18 - 54 mg once daily
- Maximum: 54 mg once daily
- Increase daily dose in increments of 18 mg at weekly intervals
- Adolescents 13 - 17 years
- Starting: 18 mg once daily
- Maintenance: 18 - 72 mg once daily
- Maximum: 72 mg once daily or 2 mg/kg/day, whichever is lower
- Increase daily dose in increments of 18 mg at weekly intervals
- Adults 18 - 65 years
- Starting: 18 - 36 mg once daily
- Maintenance: 18 - 72 mg once daily
- Maximum: 72 mg once daily
- Increase daily dose in increments of 18 mg at weekly intervals
Switching from regular methylphenidate to Concerta
Methylphenidate dose | Concerta dose |
---|---|
5 mg 2 - 3 times a day | 18 mg |
10 mg 2 - 3 times a day | 36 mg |
15 mg 2 - 3 times a day | 54 mg |
20 mg 2 - 3 times a day | 72 mg |
Generic / Price
- YES/$$ (#30)Other
- May take without regard to food
- Do not cut, chew, or dissolve tablet
- Nonabsorbable tablet shell may be seen in stool. This is normal.
Pharmacokinetics
- Time to max level: 6 - 10 hours
- Half-life: 3.5 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 2% are listed
Children ( ≥ 6 years old) | ||
---|---|---|
Side effect | Concerta | Placebo |
Upper abdominal pain | 6.2% | 3.8% |
Vomiting | 2.8% | 1.6% |
Nasopharyngitis | 2.8% | 2.2% |
Insomnia | 2.8% | 0.3% |
Fever | 2.2% | 0.9% |
Adults | ||
---|---|---|
Side effect | Concerta | Placebo |
Headache | 22.2% | 15.6% |
Dry mouth | 14% | 3.8% |
Nausea | 12.8% | 3.3% |
Insomnia | 12.3% | 6.1% |
Dizziness | 6.7% | 5.2% |
Weight loss | 6.5% | 3.3% |
Irritability | 5.8% | 1.4% |
Excessive sweating | 5.1% | 0.9% |
Rapid heart rate | 4.8% | 0% |
Depressed mood | 3.9% | 1.4% |
Nervousness | 3.1% | 0.5% |
Restlessness | 3.1% | 0% |
Palpitations | 3.1% | 0.9% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Gastrointestinal obstruction - Concerta is formulated in a non deformable tablet and could potentially cause obstruction in patients with GI motility issues (ex. strictures, short gut syndrome, cystic fibrosis, Meckel's diverticulum)
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome. In a study lasting 27 months, the cumulative incidence of new onset tics was 9% with Concerta.
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Cotempla XR-ODT™ (methylphenidate hydrochloride)
Dosage forms
Orally disintegrating tablet, extended-release
- 8.6 mg
- 17.3 mg
- 25.9 mg
- Comes packaged in blister cards with 6 tablets
Dosing
ADHD (6 - 17 years old)
- Starting: 17.3 mg once daily
- Maximum: 51.8 mg once daily
- Increase daily dose in increments of 8.6 mg at weekly intervals
- Leave tablet in blister pack until ready to take. Do not push the tablet through the foil. Peel foil back.
- Tablet is placed on tongue where it dissolves. Tablet should not be crushed or chewed.
- Take consistently either with or without food. Food decreases the peak concentration but increases exposure.
Generic / Price
- NO/$$$$ (#30)Pharmacokinetics
- Time to max level: 5 hours
- Half-life: 4 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indication
- ADHDSide effects
- The Cotempla XR-ODT PI does not give the incidence of side effects and only states that side effects with Cotempla appear similar to other methylphenidate extended-release products. See Aptensio side effects for side effects from another extended-release methylphenidate product.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Acid-reducing drugs (e.g. PPIs, antacids, H2 blockers) - DO NOT COMBINE. These drugs may alter the release profile and change the pharmacodynamics of Cotempla XR-ODT.
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - has not been studied. Manufacturer makes no specific dosage recommendation.
- Kidney disease - has not been studied. Manufacturer states that since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of Cotempla.
Daytrana® (methylphenidate hydrochloride)
Dosage forms
Patch
- 10 mg/9 hours (1.1 mg/hr)
- 15 mg/9 hours (1.6 mg/hr)
- 20 mg/9 hours (2.2 mg/hr)
- 30 mg/9 hours (3.3 mg/hr)
Dosing
ADHD ( ≥ 6 years old)
- Titrate to dose that achieves desired effect
- Week 1: 10 mg patch
- Week 2: 15 mg patch
- Week 3: 20 mg patch
- Week 4: 30 mg patch
- Patch is applied to the hip area 2 hours before effect is needed
- Patch is removed after 9 hours
Generic / Price
- YES/$$$$ (#30)Other
- Rotate application sites daily between hips
- Avoid exposing patch to heat. Heat may increase absorption and drug exposure.
- Oil-based products (petroleum jelly, olive oil, or mineral oil) may be used to help remove the patch
- Showering, swimming, and water exposure can affect patch adherence
- Used patches should be folded and flushed down the toilet to prevent accidental exposure
Pharmacokinetics
- Time to max level: 10 hours after single application; 8 hours after repeat application
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 2% are listed.
Children ( ≥ 6 years old) | ||
---|---|---|
Side effect | Daytrana | Placebo |
Decreased appetite | 25.5% | 4.7% |
Headache | 15.3% | 11.8% |
Insomnia | 13.3% | 4.7% |
Nausea | 12.2% | 2.4% |
Vomiting | 10.2% | 4.7% |
Weight decrease | 9.2% | 0% |
Abdominal pain | 7.1% | 5.9% |
Tics | 7.1% | 0% |
Irritability | 7.1% | 4.7% |
Application site reactions | 6.7% | N/A |
Affect lability | 6.1% | 0% |
Anorexia | 5.1% | 1.2% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Loss of skin color - Daytrana patch has caused permanent loss of skin color in some patients. In most cases, the loss of skin color was limited to the areas around where the patch was rotated. Time of onset for skin color loss ranged from 2 months to 4 years. This condition is referred to as chemical leukoderma. If patients notice changes in skin color, they should contact their healthcare provider immediately. [FDA drug safety communication]
- Contact sensitization - Daytrana may cause sensitization to methylphenidate in rare cases. Signs of contact sensitization include erythema, edema, papules, and vesicles at the application site that do not improve within 48 hours or spread beyond the patch site.
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Focalin® | Focalin XR® (dexmethylphenidate)
Dosage forms
Tablet (Focalin®)
- 2.5 mg
- 5 mg
- 10 mg
Capsule, extended-release (Focalin XR®)
- 5 mg
- 10 mg
- 15 mg
- 20 mg
- 25 mg
- 30 mg
- 35 mg
- 40 mg
Dosing - Focalin®
ADHD (≥ 6 years old)
- Starting: 2.5 mg twice daily
- Maximum: 10 mg twice daily
- Doses should be given at least 4 hours apart
- Increase dose by 2.5 - 5 mg at weekly intervals
- For patients switching from methylphenidate, the recommended starting Focalin dose is one-half the methylphenidate dose
- May take without regard to food
Dosing - Focalin XR®
ADHD (6 - 17 years old)
- Starting: 5 mg once daily
- Maximum: 30 mg once daily
- Increase dose by 5 mg at weekly intervals
- For patients switching from methylphenidate, the recommended starting Focalin XR dose is one-half the methylphenidate dose
- When switching from Focalin, total daily Focalin dose can be given as once daily Focalin XR dose
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
- May take without regard to food
ADHD (adults)
- Starting: 10 mg once daily
- Maximum: 40 mg once daily
- Increase dose by 10 mg at weekly intervals
- For patients switching from methylphenidate, the recommended starting Focalin XR dose is one-half the methylphenidate dose
- When switching from Focalin, total daily Focalin dose can be given as once daily Focalin XR dose
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
- May take without regard to food
Generic / Price
- Focalin® tablet - YES/$ (#60)
- Focalin XR® capsule - YES/$$ (#30)
Pharmacokinetics
Focalin®
- Time to max level: 1 - 1.5 hours
- Half-life: 2.2 hours
Focalin XR®
- Time to max level: bimodal
- First: 1.5 hours
- Second: 6.5 hours
- Half-life: 2 - 4.5 hours
Mechanism of action
- Dexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate
- Dexmethylphenidate is a CNS stimulant
- Dexmethylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space
- The mode of therapeutic action in ADHD is not known
FDA-approved indications
- ADHDSide effects
Children | ||
---|---|---|
Side effect | Focalin XR | Placebo |
Gastrointestinal disorders | 38% | 19% |
Decreased appetite | 30% | 9% |
Psychiatric disorders | 26% | 15% |
Headache | 25% | 11% |
Upset stomach | 8% | 4% |
Anxiety | 6% | 0% |
Adults | ||
---|---|---|
Side effect | Focalin XR 40 mg/day | Placebo |
Psychiatric disorders | 46% | 30% |
Gastrointestinal disorders | 44% | 19% |
Headache | 39% | 19% |
Dry mouth | 20% | 4% |
Anxiety | 11% | 2% |
Upset stomach | 9% | 2% |
Pharyngolaryngeal pain | 7% | 2% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Heartburn medications (antacids, PPIs, H2 antagonists, etc.) - heartburn medications may alter the absorption of Focalin XR
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - stimulants may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. In adult trials, the average diastolic blood pressure increased by 2 mmHg and the average heart rate increased by 6 bpm in patients treated with Focalin XR 40 mg. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Jornay PM® (methylphenidate hydrochloride)
Dosage forms
Capsule, extended-release
- 20 mg
- 40 mg
- 60 mg
- 80 mg
- 100 mg
Dosing
ADHD ( ≥ 6 years old )
- Starting: 20 mg once daily in the evening
- Maximum: 100 mg once daily in the evening
- Increase daily dose in increments of 20 mg at weekly intervals
- Initiate dosing at 8:00 PM. Adjust the timing of administration between 6:30 PM and 9:30 PM to optimize the tolerability and efficacy the next morning and throughout the day. Do not give in the morning.
- Missed doses: Patients who miss their dose at the regularly scheduled time should take it as soon as they remember that same evening. If a patient remembers the missed dose the following morning, they should skip the missed dose and wait until their next scheduled evening dose.
- Capsule may be opened, and the entire contents sprinkled onto applesauce. Applesauce should be consumed immediately without chewing.
- Jornay PM is not equivalent to other methylphenidate products on a mg-to-mg basis
- Take consistently, either with or without food
Generic / Price
- NO/$$$$ (#30)Pharmacokinetics
- Time to max level: 14 hours
- Half-life: 5.9 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHD ( ≥ 6 years old )Side effects
- NOTE: Only side effects that occurred at an incidence of ≥ 4% and more than placebo are listed.
Children ( ≥ 6 years old ) | ||
---|---|---|
Side effect | Jornay PM (N=81) |
Placebo (N=80) |
Insomnia | 33% | 9% |
Decreased appetite | 19% | 4% |
Headache | 10% | 5% |
Vomiting | 9% | 6% |
Blood pressure increase | 7% | 4% |
Mood swings | 6% | 1% |
Nausea | 6% | 0% |
Hyperactivity | 5% | 1% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
- Kidney disease - has not been studied. Manufacturer states that renal insufficiency is expected to have little effect on Jornay's pharmacokinetics.
Metadate CD® (methylphenidate hydrochloride)
Dosage forms
Capsule, extended-release
- 10 mg
- 20 mg
- 30 mg
- 40 mg
- 50 mg
- 60 mg
Dosing
ADHD ( ≥ 6 years old )
- Starting: 20 mg once daily
- Maximum: 60 mg once daily
- Increase daily dose in increments of 10 - 20 mg at weekly intervals
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
- May take without regard to food
Generic / Price
- YES/$$ (#30)Pharmacokinetics
Time to max level: bimodal
- First: 1.5 hours
- Second: 4.5 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHDSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 5% and more than placebo are listed.
Children ( ≥ 6 years old) | ||
---|---|---|
Side effect | Metadate CD | Placebo |
Headache | 12% | 8% |
Loss of appetite | 9% | 2% |
Abdominal pain | 7% | 4% |
Insomnia | 5% | 2% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Methylin® | Methylin ER® (methylphenidate hydrochloride)
Dosage forms
Tablet, chewable (Methylin®)
- 2.5 mg
- 5 mg
- 10 mg
Tablet, extended-release (Methylin ER®)
- 10 mg
- 20 mg
Solution
- 10 mg/5 ml (2 mg/ml)
- 5 mg/5 ml (1 mg/ml)
Dosing - Methylin®
ADHD and Narcolepsy
- ≥ 6 years old
- Starting: 5 mg given before breakfast and lunch
- Maximum: 60 mg a day
- Increase daily dose in increments of 5 - 10 mg at weekly intervals
- Adults
- Typical dose is 10 mg given 2 to 3 times a day
- Maximum: 60 mg a day
- Doses should be given 30 - 45 minutes before a meal
- Take last dose before 6 pm to prevent insomnia
Dosing - Methylin ER®
ADHD and Narcolepsy
- Methylin ER tablets have a duration of action of 8 hours
- They may be used to replace immediate-release methylphenidate tablets where appropriate
Generic / Price
- Tablet, extended-release - YES/$ (#30)
- Chewable tablet - YES/$-$$ (#60)
- Solution - YES/$ (150 ml)
Other
- May take without regard to food
- Chewable tablet should be taken with a full glass of water to prevent choking
- Chewable tablet contains phenylalanine
Pharmacokinetics
- Time to max level: 1 - 2 hours
- Half-life: 3 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHD
- Narcolepsy
Side effects
- The incidence of side effects with Methylin are not well-defined
- Side effects of Methylin would be expected to be similar to other methylphenidate products but may not be exactly the same. See Aptensio side effects for more.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Quillivant XR® | Quillichew ER™ (methylphenidate hydrochloride)
Dosage forms
Suspension, extended-release (Quillivant XR®)
- 5 mg/ml
- Comes in bottles of 60, 120, 150, and 180 ml
Chewable tablet, extended-release (Quillichew ER™)
- 20 mg scored
- 30 mg scored
- 40 mg unscored
Dosing
ADHD ( ≥ 6 years old)
- Starting: 20 mg once daily
- Maximum: 60 mg once daily
- Increase dose in increments of 10 - 20 mg at weekly intervals
Generic / Price
- Quillivant XR® - NO/$$$$ (120 ml)
- Quillichew ER™ - NO/$$$$
Other
Quillivant XR
- May take without regard to food
- Shake bottle vigorously for at least 10 seconds before taking
- Must be reconstituted before dispensing
- Reconstituted suspension is good for 4 months
- Store at room temperature
Quillichew ER
- May take without regard to food
- Tablet should be chewed
- 20 and 30 mg tablets are scored and may be cut in half
- Do not substitute Quillichew for other methylphenidate products on a mg-to-mg basis
Pharmacokinetics
Quillivant XR
- Time to max level: 2 - 4 hours
- Half-life: ∼ 5 hours
Quillichew ER
- Time to max level: ∼ 5 hours
- Half-life: ∼ 5.2 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- ADHD in children ≥ 6 years oldSide effects
Children ( ≥ 6 years old) | ||
---|---|---|
Side effect | Quillivant XR | Placebo |
Affect lability | 9% | 2% |
Excoriation | 4% | 0% |
Insomnia | 2% | 0% |
Tic | 2% | 0% |
Decreased appetite | 2% | 0% |
Vomiting | 2% | 0% |
Motion sickness | 2% | 0% |
Eye pain | 2% | 0% |
Rash | 2% | 0% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Phenylketonuria (PKU) (Quillichew only) - Quillichew tablets contain phenylalanine (20, 30, 40 mg tablets contain 3, 4.5, and 6 mg respectively). Use caution in patients with PKU.
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Ritalin® | Ritalin LA® | Ritalin-SR® (methylphenidate hydrochloride)
Dosage forms
Tablet (Ritalin®)
- 5 mg
- 10 mg
- 20 mg
Capsule, extended-release (Ritalin LA®)
- 10 mg
- 20 mg
- 30 mg
- 40 mg
- 60 mg
Tablet, extended-release (Ritalin-SR®)
- 20 mg
Dosing - Ritalin®
ADHD and Narcolepsy
- Children ≥ 6 years
- Starting: 5 mg given before breakfast and lunch
- Maximum: 60 mg a day
- Increase daily dose in increments of 5 - 10 mg at weekly intervals
- 10 and 20 mg tablets are scored so that they can be halved
- May take without regard to food
- Adults
- Typical dose is 10 mg given 2 to 3 times a day
- Maximum: 60 mg a day
- Doses should be given 30 - 45 minutes before a meal
- Take last dose before 6 pm to prevent insomnia
- 10 and 20 mg tablets are scored so that they can be halved
- May take without regard to food
Dosing - Ritalin LA®
ADHD ( ≥ 6 years old)
- Starting: 20 mg once daily
- Maximum: 60 mg once daily
- Increase dose in increments of 10 mg at weekly intervals
- When switching from methylphenidate immediate-release products, total daily dose of methylphenidate may be given as once daily Ritalin LA dose
- Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
- Contains immediate-release beads and delayed-release beads
- May take without regard to food
Dosing - Ritalin-SR®
ADHD and Narcolepsy
- Ritalin-SR tablets have a duration of action of 8 hours
- They may be used to replace immediate-release methylphenidate tablets where appropriate
- Do not cut, crush, or chew tablet
- May take without regard to food
Studies
Generic / Price
- Ritalin® - YES/$ (#60)
- Ritalin LA® - YES (20, 30, 40mg only)/$$ (#30)
- Ritalin-SR® - YES/$ (#30)
Pharmacokinetics
Ritalin®
- Time to max level: 1 - 2 hours
- Half-life: 2 - 4 hours
Ritalin-SR®
- Time to max level: 4.7 hours
- Duration of action: 8 hours
Ritalin LA®
- Contains immediate-release beads and delayed-release beads
- Time to max level: bimodal
- 2 hours
- 5 - 7 hours
- Half-life: 2 - 4 hours
Mechanism of action
- Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
FDA-approved indications
- Ritalin and Ritalin-SR - ADHD | Narcolepsy
- Ritalin LA - ADHD
Side effects
- The incidence of side effects with Ritalin are not well-defined
- Side effects of Ritalin would be expected to be similar to other methylphenidate products but may not be exactly the same. See Aptensio side effects for more.
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
- Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
- Alpha blockers - stimulants may counteract the effects of alpha blockers
- Beta blockers - stimulants may counteract the effects of beta blockers
- Acid-suppressing drugs (antacids, PPIs, H2 antagonists, etc) - may alter the absorption of Ritalin LA
- Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
- Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
- Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
- Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
- Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
- SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
- Meperidine - stimulants may potentiate the effects of meperidine
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Antipsychotics - antipsychotics may reduce the effects of stimulants
- Lithium - lithium may block the effects of stimulants
- Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
- Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.
Lab interactions
- Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
- Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
- Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
- Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
- Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
- Seizures - stimulants may lower the seizure threshold
- Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
- Glaucoma - stimulants may worsen glaucoma
- Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
- Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
- Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
- Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
- Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
- NONSTIMULANT MEDICATIONS
Intuniv® (guanfacine)
Dosage forms
Tablet, extended-release
- 1 mg
- 2 mg
- 3 mg
- 4 mg
Dosing
ADHD (6 - 17 years old)
- Starting: 1 mg once daily
- Maintenance: 1 - 7 mg once daily (0.05 - 0.12 mg/kg/day)
- Maximum: 7 mg once daily
- Doses may be taken in the morning or evening
- Doses > 4 mg/day have not been evaluated in children (6 - 12 years), and doses > 7 mg/day have not been evaluated in adolescents (13 - 17 years)
- Increase dose in increments of 1 mg/day at weekly intervals
- If 2 or more doses are missed, consider retitrating
- When discontinuing, dose should be tapered by no more than 1 mg/day every 3 - 7 days to avoid rebound hypertension
- Do not take with high fat meals because absorption and exposure are increased
- Swallow tablet whole. Do not crush, cut, or chew.
- Intuniv should not be substituted for immediate-release guanfacine on a mg-per-mg basis because of differing pharmacokinetics
Target dose ranges
Weight (kg) | Target dosage range |
---|---|
25 - 33.9 | 2 - 3 mg/day |
34 - 41.4 | 2 - 4 mg/day |
41.5 - 49.4 | 3 - 5 mg/day |
49.5 - 58.4 | 3 - 6 mg/day |
58.5 - 91 | 4 - 7 mg/day |
> 91 | 5 - 7 mg/day |
Dosing recommendations with CYP3A4 modulators
Starting guanfacine while currently on a CYP3A4 modulator | Continuing guanfacine while adding a CYP3A4 modulator | Continuing guanfacine while stopping a CYP3A4 modulator | |
---|---|---|---|
Strong CYP3A4 inhibitor | Half the guanfacine dose | Half the guanfacine dose | Increase dose to recommended level |
Strong CYP3A4 inducer | Consider doubling the dose | Consider doubling the dose over 1 - 2 weeks | Decrease dose to recommended level over 1 - 2 weeks |
Generic / Price
- YES/$Pharmacokinetics
- Half-life: 18 hours
- Time to max level: 6 hours✝
- ✝Data from study in adults
Mechanism of action
- The sympathetic nervous system is the main "excitatory" nervous system in the body (opposite of parasympathetic system)
- Increased sympathetic activity leads to increased awareness, stress, and adrenaline
- Guanfacine stimulates alpha-2A adrenergic receptors in the brain
- Alpha-2A stimulation leads to decreased sympathetic nervous system activity
- The mechanism of guanfacine in ADHD is not completely understood
FDA-approved indications
- ADHD (as monotherapy and as adjunctive therapy to stimulant medications) in children 6 - 17 years oldSide effects
- NOTE: Only side effects that occurred at an incidence ≥ 4% and at a rate approximately twice that of placebo are listed
Children and adolescents | ||
---|---|---|
Side effect | Guanfacine 4 mg/day | Placebo |
Somnolence | 51% | 11% |
Headache | 28% | 19% |
Fatigue | 15% | 3% |
Abdominal pain | 15% | 9% |
Dizziness | 10% | 4% |
Hypotension* | 8% | 3% |
Lethargy | 7% | 3% |
Nausea | 6% | 2% |
Dry mouth | 7% | 1% |
Constipation | 4% | 1% |
Nightmare | 4% | 0% |
Decreased blood pressure and heart rate | |||
---|---|---|---|
SBP (mmHg) |
DBP (mmHg) |
Heart rate (bpm) |
|
1 mg/day | -4.3 | -3.4 | -4.8 |
2 mg/day | -5.5 | -3.3 | -3.1 |
3 mg/day | -5.4 | -4.4 | -6.5 |
4 mg/day | -8.2 | -5.4 | -8.6 |
Drug interactions
- CYP3A4 strong inhibitors/inducers - guanfacine is a CYP3A4 sensitive substrate. See Guanfacine dosing with CYP3A4 modulators for dosing recommendations with strong CYP3A4 inhibitors and inducers
- Blood pressure medications - guanfacine may potentiate the effects of blood pressure medications
- CNS depressants (ex. alcohol, anticonvulsants, antihistamines, etc.) - guanfacine may potentiate the effects of CNS depressants. Use caution.
- Drugs that slow the heart rate - guanfacine may potentiate the decrease in heart rate seen with some medications (ex. beta blockers, calcium channel blockers)
- Tizanidine (Zanaflex®) - tizanidine is an alpha-2 agonist. It should not be taken with guanfacine.
Contraindications / Precautions
- Abrupt discontinuation - increased heart rate and rebound hypertension including cases of hypertensive encephalopathy have been seen with abrupt discontinuation of guanfacine. Concomitant stimulants may increase the risk. When discontinuing, reduce daily dose by no more than 1 mg every 3 - 7 days and monitor blood pressure and heart rate.
- Decreased blood pressure and heart rate - guanfacine may decrease blood pressure and heart rate (see Side effects). Monitor heart rate and blood pressure during usage.
- Sinus node dysfunction and heart block - guanfacine may worsen sinus node dysfunction and heart block. Use caution in susceptible patients.
- Sedation and somnolence - guanfacine causes somnolence and sedation. Caution should be used before operating motor vehicles and other dangerous equipment.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
Kapvay® (clonidine)
Dosage forms
Tablet, extended-release
- 0.1 mg
Dosing
ADHD (6 - 17 years old)
- Starting: 0.1 mg at bedtime
- Maintenance: 0.1 - 0.4 mg a day
- Maximum: 0.4 mg a day
- Increase dose in increments of 0.1 mg/day at weekly intervals
- If a dose is missed, that dose should be skipped and the next dose should be taken as scheduled
- When discontinuing, dose should be tapered by 0.1 mg/day every 3 - 7 days to avoid rebound hypertension
- Swallow tablet whole. Do not crush, cut, or chew.
- May take without regard to food
Dosing guidance
Total daily dose | Morning dose | bedtime dose |
---|---|---|
0.1 mg/day | 0.1 mg | |
0.2 mg/day | 0.1 mg | 0.1 mg |
0.3 mg/day | 0.1 mg | 0.2 mg |
0.4 mg/day | 0.2 mg | 0.2 mg |
Generic / Price
- YES/$$Pharmacokinetics
- Half-life: 12.6 hours
- Time to max level: 6.5 hours
Mechanism of action
- The sympathetic nervous system is the main "excitatory" nervous system in the body (opposite of parasympathetic system)
- Increased sympathetic activity leads to increased awareness, stress, and adrenaline
- Clonidine stimulates alpha-2 adrenergic receptors in the brain
- Alpha-2 stimulation leads to decreased sympathetic nervous system activity
- The mechanism of clonidine in ADHD is not completely understood
FDA-approved indications
- ADHD (as monotherapy and as adjunctive therapy to stimulant medications) in children 6 - 17 years oldSide effects
- NOTE: Only side effects that occurred at an incidence ≥ 3% and ≥ 3% more than placebo are listed
Children and adolescents | ||
---|---|---|
Side effect | Kapvay 0.4 mg/d | Placebo |
Somnolence | 31% | 4% |
Fatigue | 13% | 1% |
Nightmare | 9% | 0% |
Insomnia | 6% | 1% |
Constipation | 6% | 0% |
Dry mouth | 5% | 1% |
Slow heart rate* | 4% | 0% |
Emotional disorder | 4% | 1% |
Bedwetting | 4% | 0% |
Tremor | 4% | 0% |
Increased heart rate | 3% | 0% |
Tearfulness | 3% | 0% |
Decreased blood pressure and heart rate | |||
---|---|---|---|
SBP (mmHg) |
DBP (mmHg) |
Heart rate (bpm) |
|
0.2 mg/day | -4 | -4 | -4 |
0.4 mg/day | -8.8 | -7.3 | -7.7 |
Drug interactions
- Tricyclic antidepressants - tricyclic antidepressants may counteract clonidine's hypotensive effects
- Blood pressure medications - clonidine may potentiate the effects of blood pressure medications
- CNS depressants (ex. alcohol, anticonvulsants, antihistamines, etc.) - clonidine may potentiate the effects of CNS depressants. Use caution.
- Drugs that slow the heart rate - clonidine may potentiate the decrease in heart rate seen with some medications (ex. beta blockers, calcium channel blockers)
- Tizanidine (Zanaflex®) - tizanidine is an alpha-2 agonist. It should not be taken with clonidine.
Contraindications / Precautions
- Rebound hypertension - rebound hypertension may occur with abrupt discontinuation. When discontinuing, reduce dose by no more than 0.1 mg every 3 - 7 days.
- Decreased blood pressure and heart rate - clonidine may decrease blood pressure and heart rate (see Side effects). Monitor heart rate and blood pressure during usage.
- Sinus node dysfunction and heart block - clonidine may worsen sinus node dysfunction and heart block. Use caution in susceptible patients.
- Sedation and somnolence - clonidine causes somnolence and sedation in up to 38% of patients. Caution should be used before operating motor vehicles and other dangerous equipment.
- Kidney disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
- Liver disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
Qelbree® (viloxazine)
Dosage forms
Capsule
- 100 mg
- 150 mg
- 200 mg
Dosing
ADHD (6 - 11 years old)
- Starting: 100 mg once daily
- Maintenance: 100 - 400 mg once daily
- Maximum: 400 mg once daily
- Increase dose by 100 mg at weekly intervals
- May take without regard to food
- Measure blood pressure and heart rate before beginning therapy, after dose increases, and periodically thereafter
- Screen patients for suicidal ideation, depression, and bipolar before beginning therapy
- Capsules may be opened and contents sprinkled over a teaspoon of applesauce. Consume without chewing within 2 hours.
ADHD (12 - 17 years)
- Starting: 200 mg once daily
- Maintenance: 200 - 400 mg once daily
- Maximum: 400 mg once daily
- Increase dose by 200 mg at weekly intervals
- May take without regard to food
- Measure blood pressure and heart rate before beginning therapy, after dose increases, and periodically thereafter
- Screen patients for suicidal ideation, depression, and bipolar before beginning therapy
- Capsules may be opened and contents sprinkled over a teaspoon of applesauce. Consume without chewing within 2 hours.
ADHD (adults)
- Starting: 200 mg once daily
- Maintenance: 200 - 600 mg once daily
- Maximum: 600 mg once daily
- Increase dose by 200 mg at weekly intervals
- May take without regard to food
- Measure blood pressure and heart rate before beginning therapy, after dose increases, and periodically thereafter
- Screen patients for suicidal ideation, depression, and bipolar before beginning therapy
- Capsules may be opened and contents sprinkled over a teaspoon of applesauce. Consume without chewing within 2 hours.
Kidney disease dosing
- CrCl ≥ 30 ml/min: no dose adjustment necessary
- CrCl < 30 ml/min: starting dosage is 100 mg once daily. Dosage may be titrated in weekly increments of 50 to 100 mg once daily, to a maximum recommended dosage of 200 mg once daily.
Efficacy
Generic / Price
- NO/$$$$Pharmacokinetics
- Half-life: 7 hours
- Time to max level: 5 hours
Mechanism of action
- The mechanism of action of viloxazine in the treatment of ADHD is unclear; however, it is thought to be through inhibiting the reuptake of norepinephrine.
FDA-approved indications
- ADHD in adults and pediatric patients 6 years and olderSide effects
- NOTE: Only side effects that occurred at an incidence of ≥ 2% and more than placebo are listed. Side effect incidence for viloxazine represents all doses combined.
Pediatric patients (6 - 17 years) | ||
---|---|---|
Side effect | Viloxazine (N=826) |
Placebo (N=463) |
Somnolence | 16% | 4% |
Headache | 11% | 7% |
Decreased appetite | 7% | 0.4% |
URI | 7% | 6% |
Fatigue | 6% | 2% |
Abdominal pain | 5% | 4% |
Nausea | 5% | 3% |
Vomiting | 4% | 2% |
Insomnia | 4% | 1% |
Irritability | 3% | 1% |
Fever | 2% | 0.2% |
Weight effects
|
Adults | ||
---|---|---|
Side effect | Viloxazine (N=189) |
Placebo (N=183) |
Insomnia | 23% | 7% |
Headache | 17% | 7% |
Nausea | 12% | 3% |
Fatigue | 12% | 3% |
Decreased appetite | 10% | 3% |
Dry mouth | 10% | 2% |
Constipation | 6% | 1% |
Somnolence | 6% | 2% |
Vomiting | 4% | 1% |
Tachycardia | 4% | 1% |
Dizziness | 4% | 2% |
Irritability | 4% | 3% |
GERD | 2% | 1% |
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and viloxazine can cause hypertensive crisis. Do not take a viloxazine within 14 days of discontinuing an MAO inhibitor.
- CYP1A2 substrates - viloxazine is a strong CYP1A2 inhibitor, and it may increase exposure to sensitive CYP1A2 substrates. Do not combine viloxazine with CYP1A2 sensitive substrates or substrates with a narrow therapeutic range (e.g. alosetron, duloxetine, ramelteon, tasimelteon, tizanidine, theophylline). When combining with other substrates, dose reductions may be necessary (e.g. clozapine, pirfenidone).
- CYP2D6 substrates - viloxazine is a weak CYP2D6 inhibitor, and it may increase exposure to CYP2D6 substrates. Monitor for adverse reactions and adjust doses as necessary when combining viloxazine with CYP2D6 substrates (e.g. atomoxetine, desipramine, dextromethorphan, nortriptyline, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone)
- CYP3A4 substrates - viloxazine is a weak CYP3A4 inhibitor, and it may increase exposure to CYP3A4 substrates. Monitor for adverse reactions and adjust doses as necessary when combining viloxazine with CYP3A4 substrates.
- Blood pressure medications - viloxazine may raise blood pressure and counteract the effects of blood pressure medications
Contraindications / Precautions
- Suicidal ideation - in pediatric trials, suicidal ideation was reported in 0.9% of viloxazine-treated patients and 0.4% of placebo-treated patients. In adult trials (N=189), suicidal ideation was reported in 1.6% of viloxazine-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients, and monitor patients for mood disorders/suicidal ideation during therapy.
- Blood pressure increases - in trials involving patients 12 to 17 years of age, DBP increases of ≥ 15 mmHg at any time occurred in 25% of patients treated with viloxazine 400 mg compared to 13% of placebo-treated patients. In adult trials, 13% of viloxazine-treated patients had a DBP increase ≥ 15 mmHg at any time compared to 9% of placebo-treated patients. Blood pressure should be measured before starting therapy, after dose increases, and periodically thereafter.
- Heart rate increases - in trials involving patients 6 to 11 years of age, heart rate increases of ≥ 20 bpm at any time occurred in 28% of patients treated with viloxazine 400 mg compared to 23% of placebo-treated patients. In trials involving patients 12 to 17 years of age, heart rate increases of ≥ 20 bpm at any time occurred in 34% of patients treated with viloxazine 400 mg compared to 17% of placebo-treated patients. In adult trials, 29% of viloxazine-treated patients had a ≥ 20 bpm increase in heart rate at any time compared to 13% of placebo-treated patients. Heart rate should be measured before starting therapy, after dose increases, and periodically thereafter.
- Psychosis and mania - noradrenergic drugs like viloxazine can induce mania in patients with bipolar disorder. Use caution in susceptible patients and screen patients for bipolar symptoms before starting therapy.
- Somnolence and fatigue - in trials, somnolence and fatigue were more common in viloxazine-treated patients than placebo-treated patients. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or operating hazardous machinery, until they know how viloxazine will affect them.
- Kidney disease - see Dosing above
- Liver disease - has not been studied. Not recommended.
Strattera® (atomoxetine hydrochloride)
Dosage forms
Capsule
- 10 mg
- 18 mg
- 25 mg
- 40 mg
- 60 mg
- 80 mg
- 100 mg
Dosing
ADHD | Children ≤ 70 kg (154 lbs)
- Starting: 0.5 mg/kg/day for a minimum of 3 days
- Maintenance: 1.2 mg/kg/day
- Maximum: 1.4 mg/kg/day (do not exceed 100 mg)
- Total daily dose may be given once daily in the morning or divided and given in the morning and late afternoon/evening
- No additional benefit has been demonstrated with doses > 1.2 mg/kg/day
- Swallow capsules whole. Do not open.
- Strattera may be stopped without tapering
- May take without regard to food
- In trials, atomoxetine was studied in children down to the age of 6 years
ADHD | Adults and adolescents > 70 kg (154 lbs)
- Starting: 40 mg a day for a minimum of 3 days
- Maintenance: 80 mg a day
- Maximum: 100 mg a day
- Total daily dose may be given once daily in the morning or divided and given in the morning and late afternoon/evening
- Swallow capsules whole. Do not open.
- Strattera may be stopped without tapering
- May take without regard to food
With CYP2D6 strong inhibitors or in CYP2D6 poor metabolizers
- ADHD | Children and adolescents ≤ 70 kg (154 lbs)
- Dosing: 0.5 mg/kg/day
- Dose may be increased to 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated
- See CYP2D6 inhibitors for more
- ADHD | Adults and adolescents > 70 kg (154 lbs)
- Dosing: 40 mg a day
- Dose may be increased to 80 mg a day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated
- See CYP2D6 inhibitors for more
Generic / Price
- YES/$Pharmacokinetics
- Half-life: 5 hours
- Time to max level: 1 - 2 hours
Mechanism of action
- The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies.
FDA-approved indications
- ADHD in children ≥ 6 years old and adultsSide effects
- NOTE: Only side effects that occurred at an incidence ≥ 3% and ≥ 3% more than placebo are listed
Children and adolescents | ||
---|---|---|
Side effect | Strattera | Placebo |
Headache | 19% | 15% |
Abdominal pain | 18% | 10% |
Decreased appetite | 16% | 4% |
Somnolence | 11% | 4% |
Vomiting | 11% | 6% |
Nausea | 10% | 5% |
Fatigue | 8% | 3% |
Irritability | 6% | 3% |
Dizziness | 5% | 2% |
Weight loss | 3% | 0% |
Increase in heart rate (average bpm)
|
Adults | ||
---|---|---|
Side effect | Strattera | Placebo |
Nausea | 26% | 6% |
Dry mouth | 20% | 5% |
Decreased appetite | 16% | 3% |
Insomnia | 15% | 8% |
Fatigue | 10% | 6% |
Erectile dysfunction | 8% | 1% |
Dizziness | 8% | 3% |
Constipation | 8% | 3% |
Somnolence | 8% | 5% |
Abdominal pain | 7% | 4% |
Urinary hesitancy | 6% | 1% |
Ejaculation delay/disorder | 4% | 1% |
Excessive sweating | 4% | 1% |
Hot flash | 3% | 0% |
Chills | 3% | 0% |
Paresthesia | 3% | 0% |
Increase in heart rate (average bpm)
|
Drug interactions
- MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and atomoxetine can cause hypertensive crisis. Do not take a atomoxetine within 14 days of discontinuing an MAO inhibitor.
- CYP2D6 strong inhibitors - atomoxetine is a CYP2D6 sensitive substrate. See Dosing for information on dosing with concomitant CYP2D6 strong inhibitors.
- Blood pressure medications - atomoxetine may raise blood pressure and counteract the effects of blood pressure medications
- Vasopressors (e.g. dopamine, dobutamine) - atomoxetine may raise blood pressure and potentiate the effects of pressor agents
- Albuterol (oral and IV) - atomoxetine may potentiate the cardiac effects of systemically-administered albuterol (oral and IV) resulting in increased heart rate and blood pressure. These effects have not been seen with inhaled albuterol.
Contraindications / Precautions
- Narrow angle glaucoma - DO NOT USE. Atomoxetine may cause pupillary dilation.
- Pheochromocytoma - DO NOT USE. Atomoxetine may potentiate elevated blood pressure and tachyarrhythmia.
- Cardiovascular disease - atomoxetine may raise blood pressure and heart rate. Use with caution in susceptible patients.
- Suicidal ideation - in children and adolescents, atomoxetine may increase the risk of suicidal ideation. In trials, 0.4% of children reported suicidal ideation while taking atomoxetine.
- Liver toxicity - there have been rare cases of liver injury in patients taking atomoxetine. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury. Liver function testing should be performed in patients with symptoms of liver disease (e.g. pruritus, dark urine, jaundice, right upper quadrant tenderness, or unexplained flu-like symptoms)
- Suppression of growth - atomoxetine may suppress growth, particularly in prepubertal children. In trials lasting 3 years, prepubertal children (girls ≤ 8 years old, boys ≤ 9 years old) treated with atomoxetine gained an average weight of 2.1 kg less than predicted and obtained an average height of 1.2 cm less than predicted. Older children were not affected. It's unknown if atomoxetine affects adult height achieved.
- Structural heart disease and/or arrhythmias - sudden death has been reported in atomoxetine-treated children and adults with structural heart disease or other serious heart problems. Atomoxetine should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, significant arrhythmias, or other serious cardiac problems. Before initiating atomoxetine, screen patients for a family history of cardiac issues, including sudden death and arrhythmias. If patients develop symptoms of cardiac disease (e.g. chest pain, syncope, dyspnea) during therapy, prompt evaluation should be performed.
- Blood pressure and heart rate increase - atomoxetine can raise blood pressure and heart rate in children and adults (see Side effects above). Use caution in patients with hypertension, tachycardia, cardiovascular disease, and other susceptible conditions. Blood pressure and pulse should be checked before therapy, after initiation and dose increases, and periodically during treatment.
- Psychosis and mania - atomoxetine may cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes were reported in 0.2% of atomoxetine-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients, particularly those with a history of bipolar symptoms.
- Bipolar disorder - atomoxetine may exacerbate symptoms of bipolar disease (e.g. mania). Screen patients for a history of bipolar disorder or risk factors for bipolar before prescribing atomoxetine and consider the risks/benefits before prescribing.
- Aggressive behavior or hostility - atomoxetine may cause or exacerbate aggressive behavior or hostility in some patients. If such behavior occurs, consider atomoxetine as a possible causal agent and stop if necessary.
- Priapism - erections lasting more than 4 hours (priapism) have been reported in patients taking atomoxetine
- Kidney disease - no dose adjustment necessary
- Liver disease
- Moderate (Child-Pugh Class B) - initial and target dose should be reduced to 50% of normal dose
- Severe (Child-Pugh Class C) - initial and target dose should be reduced to 25% of normal dose
- DSM-5 ADHD DIAGNOSTIC CRITERIA
DSM-5 ADHD Diagnostic Criteria
Inattention
Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults
- Often fails to give close attention to details and makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
- Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures or conversations or when reading lengthy writings)
- Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction)
- Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked; does not finish schoolwork, household chores, or tasks in the workplace)
- Often has difficulty organizing tasks and activities (e.g., has difficulty managing sequential tasks and keeping materials and belongings in order; has messy, disorganized work; has poor time management; tends to fail to meet deadlines)
- Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., doing schoolwork or homework; preparing reports, completing forms, or reviewing lengthy papers)
- Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, or mobile phones)
- Is often easily distracted by extraneous stimuli (in older adolescents and adults, may include unrelated thoughts)
- Is often forgetful in daily activities (e.g., performing chores and running errands, returning telephone calls, paying bills, and keeping appointments)
Hyperactivity and impulsivity
Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults
- Often fidgets with or taps hands or feet or squirms in seat
- Often leaves seat in situations in which one is expected to remain seated (e.g., leaves his or her place in the classroom or office)
- Often runs about or climbs in situations in which it is inappropriate. (In adolescents or adults, this symptom may be limited to feeling restless.)
- Often is unable to play or engage in leisure activities quietly
- Often is “on the go,” acting as if “driven by a motor” (e.g., is unable to be still or feels uncomfortable being still for an extended period of time in restaurants or meetings; other people may perceive him or her as being restless and difficult to keep up with)
- Often talks excessively
- Often blurts out an answer before a question has been completed (e.g., completes people’s sentences and “jumps the gun” in conversations, cannot wait for next turn in conversation)
- Often has difficulty waiting his or her turn (e.g., while waiting in line)
- Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities or uses other people’s things without asking or receiving permission; adolescents or adults may intrude in or take over what others are doing)
The above symptoms from each category must meet the following criteria:
- Symptoms must be present for ≥ 6 months to a degree that is inconsistent with the person’s developmental level and that directly affects social and academic or occupational activities
- Several symptoms of inattention or hyperactivity and impulsivity were present before 12 years of age
- Symptoms occur in ≥ 2 settings (e.g., at home, school, or work or with friends or relatives)
- There is clear evidence that the symptoms interfere with or reduce the quality of social, academic, or occupational functioning
- The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better accounted for by another mental disorder (e.g., a mood disorder, an anxiety disorder, a dissociative disorder, or a personality disorder)
- ASSESSMENT TOOLS
- Childhood tool
- Link to Vanderbilt Assessment Scales
- Includes both teacher and parent forms
- Adult tool
- TREATMENT EFFECTS AND RECOMMENDATIONS
- Treatment comparisons
- A number of randomized, placebo-controlled trials have evaluated the efficacy of ADHD medications. Treatment effects are mostly subjective, and therefore, must be measured with questionnaires. Many different surveys with differing scales have been used in ADHD trials to measure the effects of medications, making it difficult to make comparisons across trials.
- A systematic review and network meta-analysis published in 2018 took outcome data from 133 double-blind ADHD trials (81 in children and adolescents, 51 in adults, and one in both) and standardized it so that the effects of different medications could be compared across trials. Outcomes were normalized using the standardized mean difference (SMD), which is the average difference between treatment and control groups divided by the pooled standard deviation of the two groups. This method expresses the effect size relative to the study's variability, allowing for comparisons between studies that use different outcome measures. Results from the analysis are presented in the table below.
Effects of ADHD Medications in Controlled Trials | ||
---|---|---|
Drug | Children | Adults |
Amphetamines | 1.02 (1.19 to 0.85) |
0.79 (0·99 to 0·58) |
Bupropion | 0.96 (1.69 to 0.22) |
0.46 (0·85 to 0·07) |
Methylphenidate | 0.78 (0.93 to 0.62) |
0.49 (0·64 to 0·35) |
Clonidine | 0.71 (1.17 to 0.24) |
N/A |
Guanfacine | 0.67 (0.85 to 0.50) |
N/A |
Atomoxetine | 0.56 (0.66 to 0.45) |
0.45 (0.58 to 0.32) |
- AAP recommendations for children
- Children 4 - 5 years old
- First line: parental training in behavior management and behavioral classroom interventions, or both (see CDC information on ADHD for more)
- Second line: methylphenidate [Based on PMID 17023867]
- Children 6 - 18 years old
- Medications + parent/classroom behavioral management when appropriate (see CDC information on ADHD for more)
- Medications in descending order according to strength of evidence: stimulants, atomoxetine, extended-release guanfacine, extended-release clonidine [8]
- NICE guidelines for adults
- First line: lisdexamfetamine (Vyvanse®) or methylphenidate. For patients who do not respond to one therapy after 6 weeks, consider switching to the other.
- Second line: atomoxetine [9]
- STUDIES
- STUDY
- Design: Registry cohort study (N=337,919) in patients with ADHD who were treated with methylphenidate or amphetamine
- Exposure: Amphetamine vs Methylphenidate
- Primary outcome: New diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis
- Results:
- Primary outcome: Amphetamine - 0.21%, Methylphenidate - 0.10% (HR 1.65, 95%CI [1.31 - 2.09])
- Findings: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate.
- STUDY
- Design: Registry cohort study (N=801,838) in patients with ADHD
- Exposure: ADHD medications
- Primary outcome: Risk of seizure
- Findings: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.
- STUDY
- Design: Meta-analysis of double-blind, randomized, placebo-controlled trials (Studies=22, N=2385) of stimulants in children with ADHD
- Treatment: Stimulant medication vs Placebo
- Primary outcome: Risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo
- Findings: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.
- STUDY
- Design: Retrospective cohort registry study (N=1,200,438) in children and young adults with ADHD
- Exposure: ADHD medications
- Primary outcome: Serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke)
- Findings: This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low.
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $151
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- 1 - Manufacturer's Package Insert for each drug listed
- 2 - PMID 24571756 NEJM review
- 3 - PMID 25180281 height study
- 4 - PMID 20605163 height study
- 5 - PMID 16040876 - height MA
- 6 - PMID 24224626 - NEJM Adult ADHD review
- 7 - PMID 30097390 - Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis, Lancet Psychiatry (2018)
- 8 - PMID 31570648 - Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents, Pediatris (2019)
- 9 - NICE ADHD guidelines