ADHD MEDICATIONS




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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



  • Weight loss is directly proportional to dose. In studies, average weight loss was 1.1 pound after 4 weeks for 10 mg dose and 2.8 pounds after 4 weeks for 20 mg dose
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

- ADHD

Side effects


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

Extended-release suspension
  • 2.5 mg/ml
  • Comes in 464 ml bottle
  • Suspension is bubblegum flavored
  • 2.5 mg of Dyanavel has the same amount of amphetamine found in a 4 mg strength amphetamine mixed salts product
  • Contains 3.2:1 ratio of d- to l-amphetamine
  • Store at room temperature. Shake bottle before giving.

Dosing

ADHD ( ≥ 6 years old)
  • Starting: 2.5 - 5 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
  • May take without regard to food

Generic / Price

- NO/$$$$

Pharmacokinetics (adults)

Half-life:
  • d isomer ∼ 12 hours
  • l isomer ∼ 15 hours
Time to max level: 4 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

- ADHD

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
Time to max level: 7- 10 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

Side effects



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


  • Average weight loss after 4 weeks of therapy was 0.9, 1.9, and 2.5 pounds, respectively, for patients receiving 30 mg, 50 mg, and 70 mg
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%
  • Average weight loss after 4 weeks of therapy was 2.8 pounds, 3.1 pounds, and 4.3 pounds, respectively, for patients receiving final doses of 30 mg, 50 mg, and 70 mg
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



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
Half-life: 7 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

Side effects


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
Half-life: 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

- ADHD

Side effects


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 old

Side effects




  • Only side effects that occurred at an incidence of ≥ 5% and twice the incidence of placebo are listed.
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%
  • Only side effects that occurred at an incidence of ≥ 3% and ≥ 3% more than placebo are listed.
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

- ADHD

Side effects


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

- ADHD

Side 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

- NO/$$$$ (#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

- ADHD

Side effects



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

- ADHD

Side effects



  • Only side effects that occurred at an incidence of ≥ 5% and twice the incidence of placebo are listed.
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%
  • Only side effects that occurred at an incidence of ≥ 3% and ≥ 3% more than placebo are listed.
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



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
Half-life: 6.8 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

- ADHD

Side effects



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 old

Side 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.



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

  • See CYP3A4 for a list of inducers and inhibitors
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 old

Side effects



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%
  • Values are maximum average change from baseline
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 old

Side effects



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%
  • Values are placebo-subtracted mean change
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 older

Side effects



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
  • In studies lasting 6 to 8 weeks, viloxazine-treated patients 6 to 11 years of age gained an average of 0.2 kg, compared to a gain of 1 kg in same-aged patients who received placebo. Viloxazine-treated patients 12 to 17 years of age lost an average of 0.2 kg, compared to a weight gain of 1.5 kg in same-aged patients who received placebo.
Increase in blood pressure and heart rate
  • See Precautions below
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 adults

Side effects



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)
  • Extensive CYP2D6 metabolizers: 5 bpm
  • Poor CYP2D6 metabolizers: 9.4 bpm
Increase in blood pressure ( ≥ 15 - 20 mmHg)
  • 5 - 10% of patients in trials
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)
  • Extensive CYP2D6 metabolizers: 7.5 bpm
  • Poor CYP2D6 metabolizers: 11 bpm
Increase in blood pressure (average mmHg)
  • Extensive CYP2D6 metabolizers: DBP 2.13, SBP 2.4
  • Poor CYP2D6 metabolizers: DBP 4.21, SBP 2.75


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 - sudden death has been reported in patients taking atomoxetine with structural heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - atomoxetine may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • 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

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)







  • Effect sizes are expressed as the SMD (95%CI)
  • SMD - standardized mean difference which represents the standarized treatment effect
  • Reference [7]
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)











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