ADHD MEDICATIONS









Adderall® | Adderall XR® (amphetamine salts)

Dosage forms
Adderall® tablet
  • 5 mg
  • 7.5 mg
  • 10 mg
  • 12.5 mg
  • 15 mg
  • 20 mg
  • 30 mg
Adderall XR® extended-release capsule
  • 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 tablet
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 capsule
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
  • Amphetamines are 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
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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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
Adzenys XR-ODT™ - orally disintegrating tablet
  • 3.1 mg
  • 6.3 mg
  • 9.4 mg
  • 12.5 mg
  • 15.7 mg
  • 18.8 mg
Adzenys ER™ - suspension
  • 1.25 mg/ml
  • Comes in 450 ml bottle

Dosing - ADHD
  • Children 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
  • Adolescents 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
ODT
  • Tablet is placed on 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 (ODT)
  • 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
  • Amphetamines are 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 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. Do not use within 14 days of taking 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

Precautions / Contraindications
  • Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - amphetamines may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - amphetamines may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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
Children ≥ 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
Dosing - Obesity
Children ≥ 12 years old and adults
  • Starting: 5 mg one-half hour before meals
  • Treatment should not exceed a few weeks

Generic / Price - YES/$$$$ (#60)
Other
  • May take without regard to food

Pharmacokinetics
  • Half-life: 4 - 5 hours

Mechanism of action
  • Amphetamines are CNS stimulants
  • Amphetamines are 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
  • In weight loss, amphetamines are thought to suppress appetite

FDA-approved indications
  • ADHD
  • Obesity

Side effects
NOTE: Incidence of side effects for Desoxyn are not well-defined. Desoxyn is metabolized to amphetamine. Amphetamine is a component of Adderall. Information from the Adderall XR PI is listed below. Side effects of Desoxyn would be expected to be the similar, but may not be exactly the same. 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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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® (dextroamphetamine sulfate)

Dosage forms
Dexedrine® - tablet
  • 5 mg
  • 10 mg
Dexedrine® - solution
  • 5 mg/5 ml (1 mg/ml)
Dexedrine spansule® Extended-release capsule
  • 5 mg
  • 10 mg
  • 15 mg

Dosing - Dexedrine®
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/day given in divided doses
    • Increase daily dose in increments of 5 mg at weekly intervals
  • Children ≥ 12 years old
    • Starting: 10 mg/day given in divided doses
    • 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 - Dexedrine spansule®
ADHD
  • Children ≥ 6 years old
    • Starting: 5 - 10 mg once 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 - YES/$$ (#60)
  • Dexedrine spansule® - YES/$$$ (#30)
  • Dexedrine solution - YES/$$$$ (300 ml)

Other
Dexedrine®
  • May take without regard to food
  • 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
  • Amphetamines are 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
  • Narcolepsy

Side effects
NOTE: Incidence of side effects for Dexedrine are not well-defined. Dextroamphetamine sulphate is a component of Adderall. Information from the Adderall XR PI is listed below. Side effects of Dexedrine would be expected to be the similar, but may not be exactly the same. 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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
  • Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
  • Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
  • Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.

Dyanavel XR® (amphetamine base)

Dosage forms
Extended-release suspension
  • 2.5 mg/ml
  • Comes in 464 ml bottle
  • Suspension is bubblegum flavored
  • 2.5 mg of Dyanavel has the same amount of amphetamine found in a 4 mg strength amphetamine mixed salts product
  • Contains 3.2:1 ratio of d- to l-amphetamine

Dosage - ADHD
Children ≥ 6 years old
  • Starting: 2.5 - 5 mg once daily in the morning
  • Maximum: 20 mg once daily
  • Increase dose in increments of 2.5 to 10 mg per day every 4 to 7 days
  • When switching from other amphetamine products, discontinue other product and titrate Dyanavel as above
  • Dyanavel is NOT equivalent to other amphetamine products on a mg-per-mg basis

Generic / Price - NO/$$$$
Other
  • Shake bottle before giving
  • May take without regard to food
  • Store at room temperature

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

Mechanism of action
  • Amphetamines are CNS stimulants
  • Amphetamines are 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 indication - ADHD
Side effects
NOTE: Data is from one small study (n=108) in children aged 6 - 12 years lasting 1 week. Only side effects that occurred more than placebo and at an incidence ≥ 2% are listed.

Side effect Dyanavel XR Placebo
Epistaxis 3.8% 0%
Allergic rhinitis 3.8% 0%
Upper abdominal pain 3.8% 2.1%


Drug interactions
  • MAO inhibitors - DO NOT COMBINE. Do not use within 14 days of taking 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

Precautions / Contraindications
  • Drug abuse and dependence - amphetamines have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - amphetamines may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - amphetamines may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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® (amphetamine sulphate)

Dosage forms
Tablet
  • 5 mg
  • 10 mg

Dosing - 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
Dosing - 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 - Obesity
Children ≥ 12 years old
  • 5 - 10 mg given 30 - 60 minutes before each meal
  • Usual daily dose is 30 mg

Generic / Price - NO/$$$$ (60 tablets)
Other
  • Tablets are scored and may be broken in two
  • May take without regard to food

Mechanism of action
  • Amphetamines are CNS stimulants
  • Amphetamines are 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
  • In weight loss, amphetamines are thought to suppress appetite

FDA-approved indications
  • ADHD
  • Narcolepsy
  • Obesity

Side effects
NOTE: Incidence of side effects for Evekeo are not well-defined. Amphetamine sulphate is a component of Adderall. Information from the Adderall XR PI is listed below. Side effects of Evekeo would be expected to be the similar, but may not be exactly the same. 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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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)

Extended-release capsule
  • 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
  • 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 does not affect the extent of absorption, but it slows the rate 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
  • Amphetamines are 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
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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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
Children ≥ 6 years and adults
  • Starting: 30 mg once daily
  • Maximum: 70 mg once daily
  • Increase dose in increments of 10 - 20 mg at weekly intervals
Dosing - 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
  • Amphetamines are 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
  • The mode of action in binge eating disorder is thought to occur through appetite suppression

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. Do not use within 14 days of taking 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
  • 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

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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



Aptensio XR® (methylphenidate hydrochloride)

Dosage forms
Extended-release capsule
  • 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

Generic / Price - NO/$$$$ (#30)
Other
  • May take without regard to food
  • Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.

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 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
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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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.

Concerta® (methylphenidate hydrochloride)

Dosage forms
Extended-release tablet
  • 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 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
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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • 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 - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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
Extended-release orally disintegrating tablet
  • 8.6 mg
  • 17.3 mg
  • 25.9 mg
  • Comes packaged in blister cards with 6 tablets

Dosing - ADHD
Children (6 - 17 years)
  • Starting: 17.3 mg once daily
  • Maximum: 51.8 mg once daily
  • Increase daily dose in increments of 8.6 mg at weekly intervals

Generic / Price - NO/$$$$ (#30)
Other
  • Take consistently either with or without food. Food decreases the peak concentration but increases exposure.
  • 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.

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

Mechanism of action
  • Methylphenidate is a CNS stimulant
  • Stimulants are 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 indication - ADHD
Side effects
NOTE: 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. The side effects below are what is reported in the Aptensio XR PI. 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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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
Children ≥ 6 years
  • Patch is applied to the hip area 2 hours before effect is needed
  • Patch is removed after 9 hours
Titration schedule
  • 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

Generic / Price - NO/$$$$ (#30)
Other
  • Rotate application sites daily between hips
  • Avoid exposing patch to heat. Heat may increase absorption and drug exposure.
  • Oil-based products (petroleum jelly, olive oil, or mineral oil) may be used to help remove the patch
  • Showering, swimming, and water exposure can affect patch adherence
  • Used patches should be folded and flushed down the toilet to prevent accidental exposure

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

Mechanism of action
  • Methylphenidate is a CNS stimulant
  • Stimulants are thought to 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
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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • 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.
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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
Focalin® - Tablet
  • 2.5 mg
  • 5 mg
  • 10 mg
Focalin XR® - Extended-release capsule
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 25 mg
  • 30 mg
  • 35 mg
  • 40 mg

Dosing - Focalin®
ADHD
  • Children ≥ 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
Dosing - Focalin XR®
ADHD
  • Children ≥ 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
  • 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

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

Other
Focalin®
  • May take without regard to food
Focalin XR®
  • Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
  • May take without regard to food

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 40mg/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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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

Lab interactions
  • Corticosteroid levels - stimulants may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. In adult trials, average diastolic blood pressure increase seen with Focalin XR 40 mg was ∼ 2 mmHg (SD 8 mmHg). Average heart rate increase was 6 bpm (SD 10 bpm).
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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 with methylphenidate products
  • 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.

Metadate CD® | Metadate ER® (methylphenidate hydrochloride)

Dosage forms
Metadate CD® extended-release capsule
  • 10 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 50 mg
  • 60 mg
Metadate ER® extended-release tablet
  • 20 mg

Dosing - Metadate CD®
ADHD
  • Children ≥ 6 years
    • Starting: 20 mg once daily
    • Maximum: 60 mg once daily
    • Increase daily dose in increments of 10 - 20 mg at weekly intervals
Dosing - Metadate ER®
ADHD
  • Metadate ER tablets have a duration of action of 8 hours
  • They may be used to replace immediate-release methylphenidate tablets where appropriate
  • Metadate ER is a generic version of Ritalin-SR

Generic / Price
  • Metadate CD® - YES/$$-$$$ (#30)
  • Metadate ER® - YES/$-$$ (#30)

Other
Metadate CD
  • May take without regard to food
  • Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
Metadate ER
  • May take without regard to food
  • Do not cut, crush, or chew tablet

Pharmacokinetics
Metadate CD
  • Time to max level: bimodal
    • First: 1.5 hours
    • Second: 4.5 hours
  • Half-life: 6.8 hours
Metadate ER
  • Duration of action: 8 hours

Mechanism of action
  • Methylphenidate is a CNS stimulant
  • Stimulants are 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
NOTE: Information is from the Metadate CD PI. 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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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® (methylphenidate hydrochloride)

Dosage forms
Chewable tablet
  • 2.5 mg
  • 5 mg
  • 10 mg
Solution
  • 10 mg/5 ml (2 mg/ml)
  • 5 mg/5 ml (1 mg/ml)

Dosing - 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
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

Generic / Price - YES/$$$$ (#60 tab or 600 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 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
  • Narcolepsy

Side effects
NOTE: Incidence of side effects with Methylin are not well-defined. Information from the Concerta PI is listed below. Side effects of Methylin would be expected to be the similar, but may not be exactly the same.

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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • 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
Quillivant XR® suspension
  • 5 mg/ml
  • Comes in bottles of 60, 120, 150, and 180 ml
Quillichew ER™ extended-release chewable tablet
  • 20 mg scored
  • 30 mg scored
  • 40 mg unscored

Dosing - Quillivant XR® and Quillichew ER™
ADHD
  • Children ≥ 6 years
    • 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 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 in children ≥ 6 years old
Side effects
NOTE: Data below is from trials involving Quillivant XR

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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • 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 with methylphenidate products
  • 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
Ritalin® tablet
  • 5 mg
  • 10 mg
  • 20 mg
Ritalin LA® extended-release capsule
  • 10 mg
  • 20 mg
  • 30 mg
  • 40 mg
  • 60 mg
Ritalin-SR® extended-release tablet
  • 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
  • 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 - Ritalin LA®
ADHD
  • Children ≥ 6 years
    • 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
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

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

Other
Ritalin®
  • May take without regard to food
  • 10 and 20 mg tablets are scored so that they can be halved
Ritalin LA®
  • May take without regard to food
  • Capsules may be opened and sprinkled on applesauce. Swallow applesauce whole, do not chew.
  • Contains immediate-release beads and delayed-release beads
Ritalin-SR®
  • May take without regard to food
  • Do not cut, crush, or chew tablet

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

Side effects
NOTE: Incidence of side effects with Ritalin are not well-defined. Information from the Concerta PI is listed below. Side effects of Ritalin would be expected to be the similar, but may not be exactly the same.

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. Do not use within 14 days of taking an MAO inhibitor.
  • 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
  • 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
  • Halogenated anesthetics - sudden blood pressure increases may occur during surgery

Lab interactions
  • Corticosteroid levels - methylphenidate may cause elevations in corticosteroid levels

Precautions / Contraindications
  • Drug abuse and dependence - stimulants have the potential for drug abuse and dependence. Use caution in susceptible patients.
  • Heart disease - stimulants may exacerbate and worsen heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - stimulants may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Suppression of growth - stimulant medications can 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. There is no conclusive evidence that stimulants affect adult height achieved. [1,2,3,4,5]
  • Hypertension - stimulants may raise blood pressure and worsen hypertension. Average blood pressure increase seen in trials was ∼ 2 - 4 mmHg. Average heart rate increase was 3 - 6 bpm.
  • Seizures - stimulants may lower the seizure threshold
  • Hyperthyroidism - stimulants may exacerbate symptoms of hyperthyroidism
  • Glaucoma - stimulants may worsen glaucoma
  • Psychosis - stimulants may worsen psychosis
  • Bipolar mania - stimulants may precipitate bipolar mania
  • Raynaud's phenomenon - stimulants may exacerbate Raynaud's phenomenon
  • Priapism - erections lasting more than 4 hours (priapism) have been reported with methylphenidate products
  • Tourette's syndrome and tics - stimulants may worsen motor tics and tics associated with Tourette's syndrome
  • Visual changes - difficulties with accommodation and blurring of vision have been reported with stimulant medications
  • Liver disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.
  • Kidney disease - clearance is decreased. Use caution. Manufacturer makes no dosage recommendation.



Intuniv® (guanfacine)

Dosage forms
Extended-release tablet
  • 1 mg
  • 2 mg
  • 3 mg
  • 4 mg

Dosing - ADHD
Children ≥ 6 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
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 - with concomitant CYP3A4 modulator
  • See CYP3A4 for a list of inducers and inhibitors
Guanfacine dosing recommendations with CYP3A4 modulators
Starting guanfacine while currently on a CYP3A4 modulator Continuing guanfacine while adding a CYP3A4 modulator Continuing guanfacine while stopping a CYP3A4 modulator
Strong CYP3A4 inhibitor Half the guanfacine dose Half the guanfacine dose Increase dose to recommended level
Strong CYP3A4 inducer Consider doubling the dose Consider doubling the dose over 1 - 2 weeks Decrease dose to recommended level over 1 - 2 weeks

Generic / Price - YES/$
Other
  • 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

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)
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.

Precautions / Contraindications
  • 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
Extended-release tablet
  • 0.1 mg
  • 0.2 mg

Dosing - ADHD
Children ≥ 6 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
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/$$$$
Other
  • May take without regard to food
  • Swallow tablet whole. Do not crush, cut, or chew.

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)
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.

Precautions / Contraindications
  • 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.

Strattera® (atomoxetine hydrochloride)

Dosage forms
Capsule
  • 10 mg
  • 18 mg
  • 25 mg
  • 40 mg
  • 60 mg
  • 80 mg
  • 100 mg

Dosing - ADHD
Children and adolescents ≤ 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
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
Doing - concomitant CYP2D6 strong inhibitors or in CYP2D6 poor metabolizers
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
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/$$
Other
  • May take without regard to food
  • Swallow capsules whole. Do not open.
  • Strattera may be stopped without tapering

Pharmacokinetics
  • Half-life: 5 hours
  • Time to max level: 1 - 2 hours

Mechanism of action
  • Exact mechanism is unknown, but is thought to be related to selective inhibition of the presynaptic norepinephrine transporter

FDA-approved indications - ADHD
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. Do not use within 14 days of taking an MAO inhibitor.
  • CYP2D6 strong inhibitors - atomoxetine is a CYP2D6 sensitive substrate. See Dosage 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.

Precautions / Contraindications
  • 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, pre-pubertal children (girls ≤ 8 years old, boys ≤ 9 years old) started on atomoxetine gained an average weight of 2.1 kg less than predicted and obtained an average height of 1.2 cm less than predicted. Children who were older were not affected. It's unknown if atomoxetine affects adult height achieved.
  • Structural heart disease - sudden death has been reported in patients taking atomoxetine with structural heart disease. Avoid or use caution in susceptible patients.
  • Heart arrhythmias - atomoxetine may exacerbate heart arrhythmias. Avoid use in susceptible patients.
  • Psychosis - atomoxetine may worsen psychosis
  • Bipolar mania - atomoxetine may precipitate bipolar mania
  • Priapism - erections lasting more than 4 hours (priapism) have been reported in patients taking atomoxetine
  • Kidney disease - no dose adjustment necessary
  • Liver disease
    • Moderate (Child-Pugh Class B) - initial and target dose should be reduced to 50% of normal dose
    • Severe (Child-Pugh Class C) - initial and target dose should be reduced to 25% of normal dose



DSM-5 ADHD Diagnostic Criteria

Inattention
Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults
  • Often fails to give close attention to details and makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
  • Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures or conversations or when reading lengthy writings)
  • Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction)
  • Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked; does not finish schoolwork, household chores, or tasks in the workplace)
  • Often has difficulty organizing tasks and activities (e.g., has difficulty managing sequential tasks and keeping materials and belongings in order; has messy, disorganized work; has poor time management; tends to fail to meet deadlines)
  • Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., doing schoolwork or homework; preparing reports, completing forms, or reviewing lengthy papers)
  • Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, or mobile phones)
  • Is often easily distracted by extraneous stimuli (in older adolescents and adults, may include unrelated thoughts)
  • Is often forgetful in daily activities (e.g., performing chores and running errands, returning telephone calls, paying bills, and keeping appointments)

Hyperactivity and impulsivity
Six or more of the following present in children up to 9 years; Five or more symptoms present in adolescents and adults
  • Often fidgets with or taps hands or feet or squirms in seat
  • Often leaves seat in situations in which one is expected to remain seated (e.g., leaves his or her place in the classroom or office)
  • Often runs about or climbs in situations in which it is inappropriate. (In adolescents or adults, this symptom may be limited to feeling restless.)
  • Often is unable to play or engage in leisure activities quietly
  • Often is “on the go,” acting as if “driven by a motor” (e.g., is unable to be still or feels uncomfortable being still for an extended period of time in restaurants or meetings; other people may perceive him or her as being restless and difficult to keep up with)
  • Often talks excessively
  • Often blurts out an answer before a question has been completed (e.g., completes people’s sentences and “jumps the gun” in conversations, cannot wait for next turn in conversation)
  • Often has difficulty waiting his or her turn (e.g., while waiting in line)
  • Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities or uses other people’s things without asking or receiving permission; adolescents or adults may intrude in or take over what others are doing)

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






Medication side effect studies

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.
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.
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.



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