Search drugs

ACRONYMS AND DEFINITIONS

AAP - American Academy of Pediatrics

ADHD - Attention-deficit/hyperactivity disorder

CNS - Central nervous system

CV - Cardiovascular

DSM - Diagnostic and Statistical Manual of Mental Disorders

NICE - National Institute for Health and Care Excellence

AMPHETAMINES

Adderall® | Adderall XR® (amphetamine salts)

Dosage forms

Tablet (Adderall®)

5 mg
7.5 mg
10 mg
12.5 mg

15 mg
20 mg
30 mg

Capsule, extended-release (Adderall XR®)

5 mg
10 mg
15 mg

20 mg
25 mg
30 mg

Adderall contains 4 amphetamine salts in equal parts:

Dextroamphetamine saccharate
Amphetamine aspartate
Dextroamphetamine sulfate
Amphetamine sulfate

Dosing - Adderall®

ADHD

Children 3 - 5 years old

Starting: 2.5 mg once daily
Increase daily dose in increments of 2.5 mg at weekly intervals

Children ≥ 6 years old

Starting: 5 mg once or twice daily
Increase daily dose in increments of 5 mg at weekly intervals
Doses > 40 mg a day are rare
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Narcolepsy

Children 6 - 12 years old

Starting: 5 mg once daily
Increase daily dose in increments of 5 mg at weekly intervals

Children ≥ 12 years old

Starting: 10 mg daily
Increase daily dose in increments of 10 mg at weekly intervals
Usual dose 5 - 60 mg/day
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Dosing - Adderall XR®

ADHD

Children 6 - 12 years old

Starting: 10 mg once daily
Maximum: 30 mg once daily
Increase dose in increments of 5 - 10 mg at weekly intervals

Children 13 - 17 years old

Starting: 10 mg once daily
Increase dose in increments of 10 mg at weekly intervals
In trials, doses up to 40 mg/day were used

Adults

Starting: 20 mg once daily
Increase dose in increments of 10 mg at weekly intervals
In trials, doses up to 60 mg/day were used

Generic / Price

Adderall® tablet - YES/$ (60 tablets)
Adderall XR® - YES/$ (30 capsules )

Other

Adderall®

Tablets are scored and may be broken in two
May take without regard to food

Adderall XR®

May take without regard to food
Doses should be given in the morning to prevent insomnia
When switching from Adderall, give same total daily dose as once daily Adderall XR
Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.

Pharmacokinetics

Adderall®

Half-life:

d isomer ∼ 10 hours
l isomer ∼ 13 hours

Time to max level: 3 hours

Adderall XR®

Half-life:

d isomer ∼ 10 hours
l isomer ∼ 13 hours

Time to max level: 7 hours

Mechanism of action

Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

Adderall

ADHD
Narcolepsy

Adderall XR

ADHD

Side effects

NOTE: Information from Adderall XR PI. Only side effects that occurred at an incidence of ≥ 3% and ≥ 3% more than placebo are listed.

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

NOTE: Only side effects that occurred at an overall incidence ≥ 5% and more than placebo are listed

Children 6 - 12 years
Side effect	Adzenys	Placebo
Loss of appetite	22%	2%
Insomnia	17%	2%
Abdominal pain	14%	10%
Emotional lability	9%	2%
Vomiting	7%	4%
Nervousness	6%	2%
Nausea	5%	3%
Fever	5%	2%

Adults
Side effect	Adzenys	Placebo
Dry mouth	35%	5%
Loss of appetite	33%	3%
Insomnia	27%	13%
Headache	26%	13%
Weight loss	10%	0%
Nausea	8%	3%
Agitation	8%	5%
Anxiety	8%	5%
Dizziness	7%	0%
Diarrhea	6%	0%
Tachycardia	6%	3%
Asthenia	6%	5%
Urinary tract infection	5%	0%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacid, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - amphetamines may counteract the effects of alpha blockers
Beta blockers - amphetamines may counteract the effects of beta blockers
Blood pressure medications - amphetamines may raise blood pressure and counteract the effects of blood pressure medications
Tricyclic antidepressants (TCAs) - amphetamines may potentiate the effects of TCAs and vice versa
Meperidine - amphetamines may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of amphetamines
Lithium - lithium may block the effects of amphetamines
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Desoxyn® (methamphetamine hydrochloride)

Dosage forms

Tablet

5 mg

Dosing

ADHD ( ≥ 6 years old)

Starting: 5 mg once or twice daily
Increase daily dose in increments of 5 mg at weekly intervals
Usual effective dose is 20 - 25 mg daily
Total daily dose may be given once daily or divided into two doses
May take without regard to food

Obesity ( ≥ 12 years old and adults)

Starting: 5 mg one-half hour before meals
Treatment should not exceed a few weeks

Generic / Price

- YES/$$$$ (#60)

Pharmacokinetics

Half-life: 4 - 5 hours

Mechanism of action

Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
In weight loss, amphetamines are thought to suppress appetite

FDA-approved indications

ADHD
Obesity

Side effects

The incidence of side effects with Desoxyn are not well-defined
Desoxyn is metabolized to amphetamine. Amphetamine is a component of Adderall. Side effects of Desoxyn would be expected to be similar to Adderall but may not be exactly the same. See Adderall side effects above for more.

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Dexedrine® | Dexedrine spansule® | Zenzedi® (dextroamphetamine sulfate)

Dosage forms

Tablet (Dexedrine®)

5 mg
10 mg

Solution (Dexedrine®)

5 mg/5 ml (1 mg/ml)

Capsule, extended-release (Dexedrine spansule®)

5 mg
10 mg
15 mg

Tablet (Zenzedi®)

2.5 mg
5 mg
7.5 mg
10 mg

15 mg
20 mg
30 mg

Dosing - Dexedrine® | Zenzedi®

ADHD

Children 3 - 5 years old

Starting: 2.5 mg once daily
Increase daily dose in increments of 2.5 mg at weekly intervals
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Children ≥ 6 years old

Starting: 5 mg once or twice daily
Increase daily dose in increments of 5 mg at weekly intervals
Doses > 40 mg a day are rare
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Narcolepsy

Children 6 - 12 years old

Starting: 5 mg once daily
Maintenance: 5 - 60 mg/day given in divided doses
Increase daily dose in increments of 5 mg at weekly intervals
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Children ≥ 12 years old

Starting: 10 mg once daily
Maintenance: 5 - 60 mg/day given in divided doses
Increase daily dose in increments of 10 mg at weekly intervals
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Dosing - Dexedrine spansule®

ADHD

Children ≥ 6 years old

Starting: 5 mg once or twice daily
Increase daily dose in increments of 5 mg at weekly intervals
Doses > 40 mg/day are rarely needed

Narcolepsy

Children 6 - 12 years old

Starting: 5 mg once daily
Increase daily dose in increments of 5 mg at weekly intervals

Children ≥ 12 years old

Starting: 10 mg once daily
Increase daily dose in increments of 10 mg at weekly intervals
Usual dose 5 - 60 mg/day

Generic / Price

Dexedrine® tablet (#60) - YES/$
Dexedrine spansule® (#30) - YES/$$
Dexedrine solution (150 ml) - YES/$$
Zenzedi tablet (#60) - 5 and 10 mg - YES/$ | Other doses - NO/$$$$

Other

Dexedrine®, Zenzedi®

May take without regard to food
Dexedrine tablets are scored so that they may be halved

Dexedrine spansule®

Swallow capsules whole
May take without regard to food

Pharmacokinetics

Dexedrine®

Time to max level: 3 hours
Half-life: 12 hours

Dexedrine spansule®

Time to max level: 8 hours
Half-life: 12 hours

Mechanism of action

Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

ADHD
Narcolepsy

Side effects

The incidence of side effects with Dexedrine are not well-defined
Dextroamphetamine sulphate is a component of Adderall. Side effects of Dexedrine would be expected to be similar to Adderall but may not be exactly the same. See Adderall side effects above for more.

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Dyanavel XR® (amphetamine base)

Dosage forms

Tablet, extended-release

5 mg
10 mg
15 mg
20 mg

Suspension, extended-release

2.5 mg/ml
Comes in 464 ml bottle
Suspension is bubblegum flavored
Store at room temp

Dyanavel contains amphetamine in a 3.2:1 ratio of d- to l-amphetamine
There are three active ingredients: amphetamine, dextroamphetamine sulfate, and amphetamine aspartate
Dosage strengths are expressed in terms of amphetamine base

Dosing

ADHD ( ≥ 6 years old)

Starting: 2.5 - 5 mg once daily in the morning
Maintenance: 2.5 - 20 mg once daily in the morning
Maximum: 20 mg once daily
Increase dose in increments of 2.5 to 10 mg per day every 4 to 7 days
When switching from other amphetamine products, discontinue other product and titrate Dyanavel as above
Dyanavel is NOT equivalent to other amphetamine products on a mg-per-mg basis
Tablets may be chewed or swallowed whole. The 5 mg tablet is scored for halving.
May take without regard to food

Generic / Price

Tablet and suspension: NO/$$$$

Pharmacokinetics

Half-life (adults):

d isomer: 12 - 14 hours
l isomer: 15 - 17 hours

Half-life (6 - 12 years old):

d isomer: 10.4 hours
l isomer: 12.1 hours

Time to max level: 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.

FDA-approved indication

Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older

Side effects

The incidence of side effects with Dyanavel are not well-defined
Dyanavel contains amphetamine base which is the same drug that is in Adzenys. Side effects of Dyanavel would be expected to be similar to Adzenys. See Adzenys side effects for more.

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - amphetamines may counteract the effects of alpha blockers
Beta blockers - amphetamines may counteract the effects of beta blockers
Blood pressure medications - amphetamines may raise blood pressure and counteract the effects of blood pressure medications
Tricyclic antidepressants (TCAs) - amphetamines may potentiate the effects of TCAs and vice versa
Meperidine - amphetamines may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of amphetamines
Lithium - lithium may block the effects of amphetamines
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Evekeo® | Evekeo ODT™ (amphetamine sulphate)

Dosage forms

Tablet (Evekeo®)

5 mg
10 mg

Orally disintegrating tablet (Evekeo ODT™)

5 mg
10 mg
15 mg
20 mg

Dosing - Evekeo®

ADHD

Children 3 - 5 years old

Starting: 2.5 mg once daily
Increase daily dose in increments of 2.5 mg at weekly intervals

Children ≥ 6 years old

Starting: 5 mg once or twice daily
Increase daily dose in increments of 5 mg at weekly intervals
Doses > 40 mg a day are rare
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Narcolepsy

Children 6 - 12 years old

Starting: 5 mg once daily
Increase daily dose in increments of 5 mg at weekly intervals

Children ≥ 12 years old

Starting: 10 mg daily
Increase daily dose in increments of 10 mg at weekly intervals
Usual dose 5 - 60 mg/day
Give first dose on awakening and additional doses at intervals of 4 - 6 hours

Obesity ( ≥ 12 years old)

5 - 10 mg given 30 - 60 minutes before each meal
Usual daily dose is 30 mg

Dosing - Evekeo ODT™

ADHD (6 - 17 years old)

Starting: 5 mg once or twice daily
If necessary, administer an additional dose after 4 to 6 hours
Increase daily dose in increments of 5 mg at weekly intervals
Only in rare cases will it be necessary to exceed a total of 40 mg daily

Generic / Price

Evekeo - YES/$$
Evekeo ODT - NO/$$$$

Other

Evekeo

Tablets are scored and may be broken in two
May take without regard to food

Evekeo ODT

May take without regard to food or liquid
Do not remove tablet from blister pack until ready to take
Do not cut or crush tablet
Place tablet on tongue and allow to disintegrate without chewing or crushing
Swallow dissolved tablet. No liquid is necessary.

Mechanism of action

Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.
In weight loss, amphetamines are thought to suppress appetite

FDA-approved indications

Evekeo®

ADHD
Narcolepsy
Obesity

Evekeo ODT™

ADHD

Side effects

In one small (N=105) open-label trial, the following side effects were reported for Evekeo (10 - 40 mg/day). Strength of association is not well-defined.

Decreased appetite - 28%
Infections - 22%
Abdominal pain - 15%
Irritability - 14%
Headache - 13%
Insomnia - 10%
Fatigue - 10%
Affect lability - 9%
Tachycardia - 9%
Nausea - 6%
Vomiting - 6%
Dry mouth - 6%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Mydayis™ (amphetamine salts)

Capsule, extended-release

12.5 mg
25 mg
37.5 mg
50 mg

Mydayis contains 4 amphetamine salts in equal parts:

Dextroamphetamine saccharate
Amphetamine aspartate
Dextroamphetamine sulfate
Amphetamine sulfate

Dosing

ADHD

13 - 17 years old

Starting: 12.5 mg once daily
Maximum: 25 mg once daily
Increase dose in increments of 12.5 mg at no less than weekly intervals
Administer once daily in the morning upon awakening

18 - 55 years

Starting: 12.5 mg once daily
Maximum: 50 mg once daily
A starting dose of 25 mg may be considered for some patients
Increase dose in increments of 12.5 mg at no less than weekly intervals
Administer once daily in the morning upon awakening

Generic / Price

- NO/$$$$ (30 caps)

Other

Take consistently either with food or without food. High fat meal slows the rate of absorption but does not affect the extent of absorption.
Capsules may be opened and sprinkled on applesauce. Applesauce should be swallowed immediately without chewing.

Pharmacokinetics

Half-life:

d isomer ∼ 10 - 11 hours
l isomer ∼ 10 - 13 hours

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

NOTE: Only side effects that occurred at an incidence of ≥ 3% and twice the incidence of placebo are listed.

Adolescents
Side effect	Mydayis	Placebo
Decreased appetite	22%	6%
Insomnia	8%	3%
Nausea	8%	4%
Irritability	6%	3%
Weight loss	5%	1%
Dizziness	4%	0%
Upper abdominal pain	4%	1%

Adults
Side effect	Mydayis	Placebo
Insomnia	31%	8%
Decreased appetite	30%	4%
Dry mouth	23%	4%
Weight loss	9%	0%
Heart rate increase	9%	0%
Anxiety	7%	3%
Palpitations	4%	2%
Dysmenorrhea	4%	2%
Depression	3%	0%
Diarrhea	3%	1%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - amphetamines may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Acid-reducing drugs (e.g. antacids, PPIs, H2 antagonists) - acid-reducing drugs may increase the absorption of amphetamines thereby increasing exposure and risk of adverse events
CYP2D6 inhibitors - CYP2D6 inhibitors may increase exposure to amphetamines. Start with lower doses of amphetamines and titrate slowly when combining.
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Tricyclic antidepressants (TCAs) - stimulants may potentiate the effects of TCAs and vice versa
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Urinary alkalizers (e.g. acetazolamide, metolazone) - may decrease the clearance of amphetamines and increase exposure
Acidifying agents (eg. ascorbic acid, fruit juices, ammonium chloride) - may decrease exposure to amphetamines
Phenobarbital - amphetamines may delay the absorption of phenobarbital
Phenytoin - amphetamines may delay the absorption of phenytoin

Lab interactions

Corticosteroid levels - amphetamines may cause elevations in corticosteroid levels

Contraindications / Precautions

Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no specific dosage recommendation.
Kidney disease

CrCl 15 to <30 ml/min

Adults: starting dose 12.5 mg daily; maximum 25 mg daily
Pediatric (13 - 17 years): maximum 12.5 mg daily

CrCl < 15 ml/min: DO NOT USE

Vyvanse® (lisdexamfetamine)

Dosage forms

Capsule

10 mg
20 mg
30 mg
40 mg

50 mg
60 mg
70 mg

Dosing

ADHD ( ≥ 6 years old and adults)

Starting: 30 mg once daily
Maximum: 70 mg once daily
Increase dose in increments of 10 - 20 mg at weekly intervals

Binge eating disorder (adults)

Starting: 30 mg once daily
Target: 50 - 70 mg once daily
Maximum: 70 mg once daily
Increase dose in increments of 20 mg at weekly intervals

Generic / Price

- NO/$$$$ (#30)

Other

May take without regard to food
Capsules may be opened and contents mixed with yogurt, water, or orange juice. Contents should be mixed until completely dispersed. Film coating left in glass is inactive ingredients. Active component dissolves completely.

Pharmacokinetics

Time to max level: 3.5 hours
Lisdexamfetamine is converted to dextroamphetamine
Half-life of dextroamphetamine is 12 hours

Mechanism of action

Lisdexamfetamine is a prodrug of dextroamphetamine
Amphetamines are CNS stimulants. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood. In binge eating disorder, stimulants suppress appetite.

FDA-approved indications

ADHD
Moderate to severe binge eating disorder

Side effects

NOTE: Only side effects that occurred at an incidence of ≥ 4% and twice the incidence of placebo are listed.

^✝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

METHYLPHENIDATE

Adhansia XR™ (methylphenidate hydrochloride)

Dosage forms

Capsule, extended-release

25 mg
35 mg
45 mg

55 mg
70 mg
85 mg

Dosing

ADHD ( ≥ 6 years old)

Starting: 25 mg once daily
Maximum: Pediatric - 85 mg/day | Adults - 100 mg/day
Increase dose in increments of 10 - 15 mg/day at intervals of no less than 5 days
Doses above 70 mg/day in pediatric patients and 85 mg/day in adults were associated with a disproportionate increase in side effects
Capsules may be opened and sprinkled on applesauce or yogurt. Swallow mixture whole without chewing within 10 minutes.
May take without regard to food

Generic / Price

- NO/$$$$ (#30)

Pharmacokinetics

Time to max level: bimodal

First: 1.5 hours
Second: 12 hours

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

NOTE: Only side effects that occurred at an incidence of ≥ 2% and more than placebo are listed

Children ( 12 - 17 years old)
Side effect	Adhansia 25 - 85 mg	Placebo
Decreased appetite	20%	0%
Insomnia	6%	1%
Weight loss	7%	0%
Upper abdominal pain	4%	1%
Nausea	6%	4%
Dizziness	3%	0%
Dry mouth	3%	1%
Vomiting	3%	0%

Adults
Side effect	Adhansia 25 - 100 mg	Placebo
Insomnia	16%	4%
Decreased appetite	11%	3%
Dry mouth	9%	4%
Nausea	6%	3%
Diarrhea	4%	1%
Feeling jittery	4%	1%
Weight loss	4%	1%
Upper respiratory infection	2%	1%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Acid-reducing drugs (e.g. PPIs, antacids, H2 blockers) - acid-reducing drugs may alter the release and pharmacokinetics of Adhansia. Monitor for changes in clinical effect when combining.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

FD&C Yellow No. 5 - Adhansia contains FD&C Yellow No. 5 (tartrazine) which can cause allergic reactions in susceptible patients. Patients with aspirin hypersensitivity may be at increased risk.
Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
Kidney disease - has not been studied. Renal clearance is not an important route of methylphenidate clearance, so renal insufficiency is not expected to have a significant effect on methylphenidate pharmacokinetics.

Aptensio XR® (methylphenidate hydrochloride)

Dosage forms

Capsule, extended-release

10 mg
15 mg
20 mg
30 mg

40 mg
50 mg
60 mg

Dosing

ADHD (children ≥ 6 years old)

Starting: 10 mg once daily
Maximum: 60 mg once daily
Increase daily dose in increments of 10 mg at weekly intervals
Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
May take without regard to food

Generic / Price

- NO/$$$$ (#30)

Pharmacokinetics

Time to max level: bimodal

First: 2 hours
Second: 8 hours

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

NOTE: Only side effects that occurred at an incidence of ≥ 3% are listed

Children ( ≥ 6 years old)
Side effect	Aptensio XR	Placebo
Headache	10.9%	8.5%
Insomnia	9.8%	2.1%
Upper abdominal pain	8.2%	0%
Decreased appetite	4.9%	0%
Vomiting	3.8%	0%
Nausea	3.8%	2.1%
Dizziness	2.2%	2.1%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Azstarys™ (serdexmethylphenidate and dexmethylphenidate)

Dosage forms

Capsule

26.1/5.2 mg
39.2/7.8 mg
52.3/10.4 mg

Dosing

ADHD (6 - 12 years old)

Starting: 39.2/7.8 mg once daily in the morning
Maintenance: after 1 week, increase dose to 52.3/10.4 mg, or decreased to 26.1/5.2 mg, depending on response and tolerability
Maximum: 52.3/10.4 mg once daily in the morning
May take without regard to food
Capsules may be opened and the contents sprinkled into 50 mL of water or over 2 tablespoons of applesauce. Consume within 10 minutes of mixing.
Do not substitute Azstarys for other methylphenidate products on a milligram-per-milligram basis. When switching from another methylphenidate product, discontinue that treatment, and titrate as above.

ADHD (13 - 17 years old and adults)

Starting: 39.2/7.8 mg once daily in the morning
Maintenance: after 1 week, increase dose to 52.3/10.4 mg
Maximum: 52.3/10.4 mg once daily in the morning
May take without regard to food
Capsules may be opened and the contents sprinkled into 50 mL of water or over 2 tablespoons of applesauce. Consume within 10 minutes of mixing.
Do not substitute Azstarys for other methylphenidate products on a milligram-per-milligram basis. When switching from another methylphenidate product, discontinue that treatment, and titrate as above.

Generic / Price

NO/$$$$

Pharmacokinetics

Time to max level: 2 hours (fasting) | 4.25 hours (with food)
Half-life

Serdexmethylphenidate: 5.7 hours
Dexmethylphenidate : 11.7 hours

Mechanism of action

Serdexmethylphenidate is a prodrug of dexmethylphenidate. Dexmethylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.

FDA-approved indications

- ADHD in adults and children ≥ 6 years old

Side effects

NOTE: The Azstarys PI does not give specific side effect data. The information below is from the Focalin PI. Focalin has the same active ingredient (dexmethylphenidate) as Azstarys.

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

NOTE: Only side effects that occurred at an incidence of ≥ 2% are listed

Children ( ≥ 6 years old)
Side effect	Concerta	Placebo
Upper abdominal pain	6.2%	3.8%
Vomiting	2.8%	1.6%
Nasopharyngitis	2.8%	2.2%
Insomnia	2.8%	0.3%
Fever	2.2%	0.9%

Adults
Side effect	Concerta	Placebo
Headache	22.2%	15.6%
Dry mouth	14%	3.8%
Nausea	12.8%	3.3%
Insomnia	12.3%	6.1%
Dizziness	6.7%	5.2%
Weight loss	6.5%	3.3%
Irritability	5.8%	1.4%
Excessive sweating	5.1%	0.9%
Rapid heart rate	4.8%	0%
Depressed mood	3.9%	1.4%
Nervousness	3.1%	0.5%
Restlessness	3.1%	0%
Palpitations	3.1%	0.9%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Gastrointestinal obstruction - Concerta is formulated in a non deformable tablet and could potentially cause obstruction in patients with GI motility issues (ex. strictures, short gut syndrome, cystic fibrosis, Meckel's diverticulum)
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome. In a study lasting 27 months, the cumulative incidence of new onset tics was 9% with Concerta.
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Cotempla XR-ODT™ (methylphenidate hydrochloride)

Dosage forms

Orally disintegrating tablet, extended-release

8.6 mg
17.3 mg
25.9 mg
Comes packaged in blister cards with 6 tablets

Dosing

ADHD (6 - 17 years old)

Starting: 17.3 mg once daily
Maximum: 51.8 mg once daily
Increase daily dose in increments of 8.6 mg at weekly intervals
Leave tablet in blister pack until ready to take. Do not push the tablet through the foil. Peel foil back.
Tablet is placed on tongue where it dissolves. Tablet should not be crushed or chewed.
Take consistently either with or without food. Food decreases the peak concentration but increases exposure.

Generic / Price

- NO/$$$$ (#30)

Pharmacokinetics

Time to max level: 5 hours
Half-life: 4 hours

Mechanism of action

Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indication

- 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

- YES/$$$$ (#30)

Other

Rotate application sites daily between hips
Avoid exposing patch to heat. Heat may increase absorption and drug exposure.
Oil-based products (petroleum jelly, olive oil, or mineral oil) may be used to help remove the patch
Showering, swimming, and water exposure can affect patch adherence
Used patches should be folded and flushed down the toilet to prevent accidental exposure

Pharmacokinetics

Time to max level: 10 hours after single application; 8 hours after repeat application

Mechanism of action

Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

- ADHD

Side effects

NOTE: Only side effects that occurred at an incidence of ≥ 2% are listed.

Children ( ≥ 6 years old)
Side effect	Daytrana	Placebo
Decreased appetite	25.5%	4.7%
Headache	15.3%	11.8%
Insomnia	13.3%	4.7%
Nausea	12.2%	2.4%
Vomiting	10.2%	4.7%
Weight decrease	9.2%	0%
Abdominal pain	7.1%	5.9%
Tics	7.1%	0%
Irritability	7.1%	4.7%
Application site reactions	6.7%	N/A
Affect lability	6.1%	0%
Anorexia	5.1%	1.2%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Loss of skin color - Daytrana patch has caused permanent loss of skin color in some patients. In most cases, the loss of skin color was limited to the areas around where the patch was rotated. Time of onset for skin color loss ranged from 2 months to 4 years. This condition is referred to as chemical leukoderma. If patients notice changes in skin color, they should contact their healthcare provider immediately. [FDA drug safety communication]
Contact sensitization - Daytrana may cause sensitization to methylphenidate in rare cases. Signs of contact sensitization include erythema, edema, papules, and vesicles at the application site that do not improve within 48 hours or spread beyond the patch site.
Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Focalin® | Focalin XR® (dexmethylphenidate)

Dosage forms

Tablet (Focalin®)

2.5 mg
5 mg
10 mg

Capsule, extended-release (Focalin XR®)

5 mg
10 mg
15 mg
20 mg

25 mg
30 mg
35 mg
40 mg

Dosing - Focalin®

ADHD (≥ 6 years old)

Starting: 2.5 mg twice daily
Maximum: 10 mg twice daily
Doses should be given at least 4 hours apart
Increase dose by 2.5 - 5 mg at weekly intervals
For patients switching from methylphenidate, the recommended starting Focalin dose is one-half the methylphenidate dose
May take without regard to food

Dosing - Focalin XR®

ADHD (6 - 17 years old)

Starting: 5 mg once daily
Maximum: 30 mg once daily
Increase dose by 5 mg at weekly intervals
For patients switching from methylphenidate, the recommended starting Focalin XR dose is one-half the methylphenidate dose
When switching from Focalin, total daily Focalin dose can be given as once daily Focalin XR dose
Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
May take without regard to food

ADHD (adults)

Starting: 10 mg once daily
Maximum: 40 mg once daily
Increase dose by 10 mg at weekly intervals
For patients switching from methylphenidate, the recommended starting Focalin XR dose is one-half the methylphenidate dose
When switching from Focalin, total daily Focalin dose can be given as once daily Focalin XR dose
Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
May take without regard to food

Generic / Price

Focalin® tablet - YES/$ (#60)
Focalin XR® capsule - YES/$$ (#30)

Pharmacokinetics

Focalin®

Time to max level: 1 - 1.5 hours
Half-life: 2.2 hours

Focalin XR®

Time to max level: bimodal

First: 1.5 hours
Second: 6.5 hours

Half-life: 2 - 4.5 hours

Mechanism of action

Dexmethylphenidate is the more pharmacologically active d-enantiomer of racemic methylphenidate
Dexmethylphenidate is a CNS stimulant
Dexmethylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space
The mode of therapeutic action in ADHD is not known

FDA-approved indications

- 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

NOTE: Only side effects that occurred at an incidence of ≥ 4% and more than placebo are listed.

Children ( ≥ 6 years old )
Side effect	Jornay PM (N=81)	Placebo (N=80)
Insomnia	33%	9%
Decreased appetite	19%	4%
Headache	10%	5%
Vomiting	9%	6%
Blood pressure increase	7%	4%
Mood swings	6%	1%
Nausea	6%	0%
Hyperactivity	5%	1%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - has not been studied. Manufacturer makes no dosage recommendation.
Kidney disease - has not been studied. Manufacturer states that renal insufficiency is expected to have little effect on Jornay's pharmacokinetics.

Metadate CD® (methylphenidate hydrochloride)

Dosage forms

Capsule, extended-release

10 mg
20 mg
30 mg

40 mg
50 mg
60 mg

Dosing

ADHD ( ≥ 6 years old )

Starting: 20 mg once daily
Maximum: 60 mg once daily
Increase daily dose in increments of 10 - 20 mg at weekly intervals
Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
May take without regard to food

Generic / Price

- YES/$$ (#30)

Pharmacokinetics

Time to max level: bimodal

First: 1.5 hours
Second: 4.5 hours

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

NOTE: Only side effects that occurred at an incidence of ≥ 5% and more than placebo are listed.

Children ( ≥ 6 years old)
Side effect	Metadate CD	Placebo
Headache	12%	8%
Loss of appetite	9%	2%
Abdominal pain	7%	4%
Insomnia	5%	2%

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Methylin® | Methylin ER® (methylphenidate hydrochloride)

Dosage forms

Tablet, chewable (Methylin®)

2.5 mg
5 mg
10 mg

Tablet, extended-release (Methylin ER®)

10 mg
20 mg

Solution

10 mg/5 ml (2 mg/ml)
5 mg/5 ml (1 mg/ml)

Dosing - Methylin®

ADHD and Narcolepsy

≥ 6 years old

Starting: 5 mg given before breakfast and lunch
Maximum: 60 mg a day
Increase daily dose in increments of 5 - 10 mg at weekly intervals

Adults

Typical dose is 10 mg given 2 to 3 times a day
Maximum: 60 mg a day
Doses should be given 30 - 45 minutes before a meal
Take last dose before 6 pm to prevent insomnia

Dosing - Methylin ER®

ADHD and Narcolepsy

Methylin ER tablets have a duration of action of 8 hours
They may be used to replace immediate-release methylphenidate tablets where appropriate

Generic / Price

Tablet, extended-release - YES/$ (#30)
Chewable tablet - YES/$-$$ (#60)
Solution - YES/$ (150 ml)

Other

May take without regard to food
Chewable tablet should be taken with a full glass of water to prevent choking
Chewable tablet contains phenylalanine

Pharmacokinetics

Time to max level: 1 - 2 hours
Half-life: 3 hours

Mechanism of action

Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

ADHD
Narcolepsy

Side effects

The incidence of side effects with Methylin are not well-defined
Side effects of Methylin would be expected to be similar to other methylphenidate products but may not be exactly the same. See Aptensio side effects for more.

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Quillivant XR® | Quillichew ER™ (methylphenidate hydrochloride)

Dosage forms

Suspension, extended-release (Quillivant XR®)

5 mg/ml
Comes in bottles of 60, 120, 150, and 180 ml

Chewable tablet, extended-release (Quillichew ER™)

20 mg scored
30 mg scored
40 mg unscored

Dosing

ADHD ( ≥ 6 years old)

Starting: 20 mg once daily
Maximum: 60 mg once daily
Increase dose in increments of 10 - 20 mg at weekly intervals

Generic / Price

Quillivant XR® - NO/$$$$ (120 ml)
Quillichew ER™ - NO/$$$$

Other

Quillivant XR

May take without regard to food
Shake bottle vigorously for at least 10 seconds before taking
Must be reconstituted before dispensing
Reconstituted suspension is good for 4 months
Store at room temperature

Quillichew ER

May take without regard to food
Tablet should be chewed
20 and 30 mg tablets are scored and may be cut in half
Do not substitute Quillichew for other methylphenidate products on a mg-to-mg basis

Pharmacokinetics

Quillivant XR

Time to max level: 2 - 4 hours
Half-life: ∼ 5 hours

Quillichew ER

Time to max level: ∼ 5 hours
Half-life: ∼ 5.2 hours

Mechanism of action

Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

- ADHD in children ≥ 6 years 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

Methylphenidate vs Placebo for Apathy in Patients with Alzheimers, JAMA Neurology (2021) [Pubmed Abstract]

Generic / Price

Ritalin® - YES/$ (#60)
Ritalin LA® - YES (20, 30, 40mg only)/$$ (#30)
Ritalin-SR® - YES/$ (#30)

Pharmacokinetics

Ritalin®

Time to max level: 1 - 2 hours
Half-life: 2 - 4 hours

Ritalin-SR®

Time to max level: 4.7 hours
Duration of action: 8 hours

Ritalin LA®

Contains immediate-release beads and delayed-release beads
Time to max level: bimodal

2 hours
5 - 7 hours

Half-life: 2 - 4 hours

Mechanism of action

Methylphenidate is a CNS stimulant. Stimulants are thought to increase concentrations of neurotransmitters, primarily norepinephrine and dopamine, in the synaptic space through the following mechanisms: (1) blockage of neurotransmitter reuptake by the presynaptic neuron, (2) enhancement of neurotransmitter release from the presynaptic neuron. Their mode of therapeutic action in ADHD is not completely understood.

FDA-approved indications

Ritalin and Ritalin-SR - ADHD | Narcolepsy
Ritalin LA - ADHD

Side effects

The incidence of side effects with Ritalin are not well-defined
Side effects of Ritalin would be expected to be similar to other methylphenidate products but may not be exactly the same. See Aptensio side effects for more.

Drug interactions

MAO inhibitors - DO NOT COMBINE. Concomitant use of MAO inhibitors and stimulants can cause hypertensive crisis. Do not take a stimulant within 14 days of discontinuing an MAO inhibitor.
Serotonergic drugs - methylphenidate may potentiate the effects of serotonergic drugs and increase the risk of serotonin syndrome
Alpha blockers - stimulants may counteract the effects of alpha blockers
Beta blockers - stimulants may counteract the effects of beta blockers
Acid-suppressing drugs (antacids, PPIs, H2 antagonists, etc) - may alter the absorption of Ritalin LA
Blood pressure medications - stimulants may raise blood pressure and counteract the effects of blood pressure medications. Monitor blood pressure and adjust doses of antihypertensives as needed.
Warfarin - methylphenidate may inhibit warfarin metabolism and increase exposure. Monitor INR closely with concomitant use.
Phenobarbital - methylphenidate may inhibit phenobarbital metabolism and increase exposure. Monitor levels closely with concomitant use.
Phenytoin - methylphenidate may inhibit phenytoin metabolism and increase exposure. Monitor levels closely with concomitant use.
Tricyclic antidepressants (TCAs) - methylphenidate may inhibit the metabolism of tricyclic antidepressants and increase exposure. Use caution with concomitant use.
SSRI antidepressants - methylphenidate may inhibit the metabolism of SSRI antidepressants and increase exposure. Use caution with concomitant use.
Meperidine - stimulants may potentiate the effects of meperidine
Antipsychotics - antipsychotics may reduce the effects of stimulants
Antipsychotics - antipsychotics may reduce the effects of stimulants
Lithium - lithium may block the effects of stimulants
Risperidone - combined use of methylphenidate with risperidone may increase the risk of extrapyramidal symptoms (EPS), particularly when the dose of either drug is adjusted. Monitor for EPS symptoms when combining.
Halogenated anesthetics - concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increases during surgery. Monitor blood pressure and do not give methylphenidate on the day of surgery.

Lab interactions

Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Contraindications / Precautions

Hypersensitivity reactions - hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving methylphenidate. Do not use in patients with a history of hypersensitivity to methylphenidate or any of the drug's components.
Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
Cardiovascular disease - Sudden death, stroke, and myocardial infarction have been reported in adults receiving stimulants; sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious cardiac problems. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, and other serious cardiac problems. Patients who experience exertional chest pain, unexplained syncope, or arrhythmias during therapy should be evaluated promptly.
Suppression of growth - stimulant medications can cause weight loss and suppress growth rates in children. The effect appears to be directly related to dose and length of therapy. In studies, growth rates in children taking stimulants were 1 - 2 cm/year slower than controls. It is unknown if stimulants affect adult height achieved. Patients who are not achieving height and weight goals as expected may need to have their therapy interrupted. [1,2,3,4,5]
Blood pressure and heart rate increase - stimulants may raise blood pressure and increase the heart rate. Average blood pressure increases are around 2 - 4 mmHg, and average heart rate increases are 3 - 6 bpm. Monitor patients for high blood pressure and tachycardia, and use caution in patients with pre-existing hypertension.
Seizures - stimulants may lower the seizure threshold
Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
Glaucoma - stimulants may worsen glaucoma
Psychosis and mania - stimulants may precipitate manic episodes in patients with bipolar disorder. They may also cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes occurred 0.1% of stimulant-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients.
Peripheral Vasculopathy, including Raynaud's Phenomenon - stimulants have been associated with peripheral vasculopathy, including Raynaud's phenomenon. In most patients, symptoms are mild, but rare cases of digital ulceration and soft tissue breakdown have occurred. Symptoms typically resolve with dose reductions or discontinuation. Patients should be instructed to report any unusual finger symptoms promptly (e.g. numbness, cold, color change).
Priapism - erections lasting more than 4 hours (priapism) have been reported in both adult and pediatric patients treated with methylphenidate products. In most cases, priapism occurred after dose increases during chronic treatment. It has also been reported during periods of drug withdrawal (e.g. drug holidays, discontinuation). Patients with prolonged and painful erections should seek immediate medical attention.
Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

NONSTIMULANT MEDICATIONS

Intuniv® (guanfacine)

Dosage forms

Tablet, extended-release

1 mg
2 mg
3 mg
4 mg

Dosing

ADHD (6 - 17 years old)

Starting: 1 mg once daily
Maintenance: 1 - 7 mg once daily (0.05 - 0.12 mg/kg/day)
Maximum: 7 mg once daily
Doses may be taken in the morning or evening
Doses > 4 mg/day have not been evaluated in children (6 - 12 years), and doses > 7 mg/day have not been evaluated in adolescents (13 - 17 years)
Increase dose in increments of 1 mg/day at weekly intervals
If 2 or more doses are missed, consider retitrating
When discontinuing, dose should be tapered by no more than 1 mg/day every 3 - 7 days to avoid rebound hypertension
Do not take with high fat meals because absorption and exposure are increased
Swallow tablet whole. Do not crush, cut, or chew.
Intuniv should not be substituted for immediate-release guanfacine on a mg-per-mg basis because of differing pharmacokinetics

Target dose ranges

Weight (kg)	Target dosage range
25 - 33.9	2 - 3 mg/day
34 - 41.4	2 - 4 mg/day
41.5 - 49.4	3 - 5 mg/day
49.5 - 58.4	3 - 6 mg/day
58.5 - 91	4 - 7 mg/day
> 91	5 - 7 mg/day

Dosing recommendations with CYP3A4 modulators

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

NOTE: Only side effects that occurred at an incidence ≥ 4% and at a rate approximately twice that of placebo are listed

Children and adolescents
Side effect	Guanfacine 4 mg/day	Placebo
Somnolence	51%	11%
Headache	28%	19%
Fatigue	15%	3%
Abdominal pain	15%	9%
Dizziness	10%	4%
Hypotension*	8%	3%
Lethargy	7%	3%
Nausea	6%	2%
Dry mouth	7%	1%
Constipation	4%	1%
Nightmare	4%	0%

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

NOTE: Only side effects that occurred at an incidence ≥ 3% and ≥ 3% more than placebo are listed

Children and adolescents
Side effect	Kapvay 0.4 mg/d	Placebo
Somnolence	31%	4%
Fatigue	13%	1%
Nightmare	9%	0%
Insomnia	6%	1%
Constipation	6%	0%
Dry mouth	5%	1%
Slow heart rate*	4%	0%
Emotional disorder	4%	1%
Bedwetting	4%	0%
Tremor	4%	0%
Increased heart rate	3%	0%
Tearfulness	3%	0%

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

NOTE: Only side effects that occurred at an incidence of ≥ 2% and more than placebo are listed. Side effect incidence for viloxazine represents all doses combined.

Pediatric patients (6 - 17 years)
Side effect	Viloxazine (N=826)	Placebo (N=463)
Somnolence	16%	4%
Headache	11%	7%
Decreased appetite	7%	0.4%
URI	7%	6%
Fatigue	6%	2%
Abdominal pain	5%	4%
Nausea	5%	3%
Vomiting	4%	2%
Insomnia	4%	1%
Irritability	3%	1%
Fever	2%	0.2%
Weight effects 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

NOTE: Only side effects that occurred at an incidence ≥ 3% and ≥ 3% more than placebo are listed

Children and adolescents
Side effect	Strattera	Placebo
Headache	19%	15%
Abdominal pain	18%	10%
Decreased appetite	16%	4%
Somnolence	11%	4%
Vomiting	11%	6%
Nausea	10%	5%
Fatigue	8%	3%
Irritability	6%	3%
Dizziness	5%	2%
Weight loss	3%	0%
Increase in heart rate (average bpm) 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 and/or arrhythmias - sudden death has been reported in atomoxetine-treated children and adults with structural heart disease or other serious heart problems. Atomoxetine should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, significant arrhythmias, or other serious cardiac problems. Before initiating atomoxetine, screen patients for a family history of cardiac issues, including sudden death and arrhythmias. If patients develop symptoms of cardiac disease (e.g. chest pain, syncope, dyspnea) during therapy, prompt evaluation should be performed.
Blood pressure and heart rate increase - atomoxetine can raise blood pressure and heart rate in children and adults (see Side effects above). Use caution in patients with hypertension, tachycardia, cardiovascular disease, and other susceptible conditions. Blood pressure and pulse should be checked before therapy, after initiation and dose increases, and periodically during treatment.
Psychosis and mania - atomoxetine may cause psychotic and manic symptoms (e.g. hallucinations, delusional thinking, mania) in patients without a prior history of psychotic illness or mania. In trials, psychotic or manic episodes were reported in 0.2% of atomoxetine-treated patients and 0% of placebo-treated patients. Use caution in susceptible patients, particularly those with a history of bipolar symptoms.
Bipolar disorder - atomoxetine may exacerbate symptoms of bipolar disease (e.g. mania). Screen patients for a history of bipolar disorder or risk factors for bipolar before prescribing atomoxetine and consider the risks/benefits before prescribing.
Aggressive behavior or hostility - atomoxetine may cause or exacerbate aggressive behavior or hostility in some patients. If such behavior occurs, consider atomoxetine as a possible causal agent and stop if necessary.
Priapism - erections lasting more than 4 hours (priapism) have been reported in patients taking atomoxetine
Kidney disease - no dose adjustment necessary
Liver disease

Moderate (Child-Pugh Class B) - initial and target dose should be reduced to 50% of normal dose
Severe (Child-Pugh Class C) - initial and target dose should be reduced to 25% of normal dose

DSM-5 ADHD DIAGNOSTIC CRITERIA

DSM-5 ADHD Diagnostic Criteria

Inattention

Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults

Often fails to give close attention to details and makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures or conversations or when reading lengthy writings)
Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction)
Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked; does not finish schoolwork, household chores, or tasks in the workplace)
Often has difficulty organizing tasks and activities (e.g., has difficulty managing sequential tasks and keeping materials and belongings in order; has messy, disorganized work; has poor time management; tends to fail to meet deadlines)
Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., doing schoolwork or homework; preparing reports, completing forms, or reviewing lengthy papers)
Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, or mobile phones)
Is often easily distracted by extraneous stimuli (in older adolescents and adults, may include unrelated thoughts)
Is often forgetful in daily activities (e.g., performing chores and running errands, returning telephone calls, paying bills, and keeping appointments)

Hyperactivity and impulsivity

Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults

Often fidgets with or taps hands or feet or squirms in seat
Often leaves seat in situations in which one is expected to remain seated (e.g., leaves his or her place in the classroom or office)
Often runs about or climbs in situations in which it is inappropriate. (In adolescents or adults, this symptom may be limited to feeling restless.)
Often is unable to play or engage in leisure activities quietly
Often is “on the go,” acting as if “driven by a motor” (e.g., is unable to be still or feels uncomfortable being still for an extended period of time in restaurants or meetings; other people may perceive him or her as being restless and difficult to keep up with)
Often talks excessively
Often blurts out an answer before a question has been completed (e.g., completes people’s sentences and “jumps the gun” in conversations, cannot wait for next turn in conversation)
Often has difficulty waiting his or her turn (e.g., while waiting in line)
Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities or uses other people’s things without asking or receiving permission; adolescents or adults may intrude in or take over what others are doing)

The above symptoms from each category must meet the following criteria:

Symptoms must be present for ≥ 6 months to a degree that is inconsistent with the person’s developmental level and that directly affects social and academic or occupational activities
Several symptoms of inattention or hyperactivity and impulsivity were present before 12 years of age
Symptoms occur in ≥ 2 settings (e.g., at home, school, or work or with friends or relatives)
There is clear evidence that the symptoms interfere with or reduce the quality of social, academic, or occupational functioning
The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better accounted for by another mental disorder (e.g., a mood disorder, an anxiety disorder, a dissociative disorder, or a personality disorder)

ASSESSMENT TOOLS

Childhood tool
- Link to Vanderbilt Assessment Scales
- Includes both teacher and parent forms
Adult tool

Link to ASRS scale developed by the World Health Organization

TREATMENT EFFECTS AND RECOMMENDATIONS

Treatment comparisons

A number of randomized, placebo-controlled trials have evaluated the efficacy of ADHD medications. Treatment effects are mostly subjective, and therefore, must be measured with questionnaires. Many different surveys with differing scales have been used in ADHD trials to measure the effects of medications, making it difficult to make comparisons across trials.
A systematic review and network meta-analysis published in 2018 took outcome data from 133 double-blind ADHD trials (81 in children and adolescents, 51 in adults, and one in both) and standardized it so that the effects of different medications could be compared across trials. Outcomes were normalized using the standardized mean difference (SMD), which is the average difference between treatment and control groups divided by the pooled standard deviation of the two groups. This method expresses the effect size relative to the study's variability, allowing for comparisons between studies that use different outcome measures. Results from the analysis are presented in the table below.

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)

AAP recommendations for children

Children 4 - 5 years old

First line: parental training in behavior management and behavioral classroom interventions, or both (see CDC information on ADHD for more)
Second line: methylphenidate [Based on PMID 17023867]

Children 6 - 18 years old

Medications + parent/classroom behavioral management when appropriate (see CDC information on ADHD for more)
Medications in descending order according to strength of evidence: stimulants, atomoxetine, extended-release guanfacine, extended-release clonidine [8]

NICE guidelines for adults

First line: lisdexamfetamine (Vyvanse®) or methylphenidate. For patients who do not respond to one therapy after 6 weeks, consider switching to the other.
Second line: atomoxetine [9]

STUDIES

STUDY
Risk of Psychosis with Methylphenidate or Amphetamine in ADHD, NEJM (2019) [PubMed abstract]

Design: Registry cohort study (N=337,919) in patients with ADHD who were treated with methylphenidate or amphetamine
Exposure: Amphetamine vs Methylphenidate
Primary outcome: New diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis
Results:

Primary outcome: Amphetamine - 0.21%, Methylphenidate - 0.10% (HR 1.65, 95%CI [1.31 - 2.09])

Findings: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate.

STUDY
ADHD Medications and Risk of Seizure, Neurology (2018) [PubMed abstract]

Design: Registry cohort study (N=801,838) in patients with ADHD
Exposure: ADHD medications
Primary outcome: Risk of seizure
Findings: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.

STUDY
Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials - J Am Acad Child Adolesc Psychiatry (2015) [PMID 26299294]

Design: Meta-analysis of double-blind, randomized, placebo-controlled trials (Studies=22, N=2385) of stimulants in children with ADHD
Treatment: Stimulant medication vs Placebo
Primary outcome: Risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo
Findings: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

STUDY
ADHD drugs and serious cardiovascular events in children and young adults - NEJM (2011) [PMID 22043968 ]

Design: Retrospective cohort registry study (N=1,200,438) in children and young adults with ADHD
Exposure: ADHD medications
Primary outcome: Serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke)
Findings: This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low.

PRICE ($) INFO

Pricing legend

$ = 0 - $50
$$ = $51 - $100
$$$ = $101 - $150
$$$$ = > $151

Pricing based on one month of therapy at standard dosing in an adult
Pricing based on information from GoodRX.com®
Pricing may vary by region and availability

BIBLIOGRAPHY

1 - Manufacturer's Package Insert for each drug listed
2 - PMID 24571756 NEJM review
3 - PMID 25180281 height study
4 - PMID 20605163 height study
5 - PMID 16040876 - height MA
6 - PMID 24224626 - NEJM Adult ADHD review
7 - PMID 30097390 - Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis, Lancet Psychiatry (2018)
8 - PMID 31570648 - Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents, Pediatris (2019)
9 - NICE ADHD guidelines

ADHD MEDICATIONS

Dosage forms

Dosing - Adderall®

Dosing - Adderall XR®

Generic / Price

Other

Pharmacokinetics

Mechanism of action

FDA-approved indications

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing

Generic / Price

Other

Pharmacokinetics

Mechanism of action

FDA-approved indication

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing

Generic / Price

Pharmacokinetics

Mechanism of action

FDA-approved indications

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing - Dexedrine® | Zenzedi®

Dosing - Dexedrine spansule®

Generic / Price

Other

Pharmacokinetics

Mechanism of action

FDA-approved indications

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing

Generic / Price

Pharmacokinetics

Mechanism of action

FDA-approved indication

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing - Evekeo®

Dosing - Evekeo ODT™

Generic / Price

Other

Mechanism of action

FDA-approved indications

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosing

Generic / Price

Other

Pharmacokinetics

Mechanism of action

FDA-approved indications

Side effects

Drug interactions

Lab interactions

Contraindications / Precautions

Dosage forms

Dosing

Generic / Price