Dosing & Uses
Dosage Forms & Strengths
tablet (Evekeo): Schedule II
- 5mg
- 10mg
extended-release oral tablets (Dyanavel XR): Schedule II
- 5mg
- 10mg
- 15mg
- 20mg
extended-release oral suspension (Dyanavel XR): Schedule II
- 2.5mg/mL
extended-release oral disintegrating tablet (Adzenys XR-ODT): Schedule II
- 3.1mg
- 6.3mg
- 9.4mg
- 12.5mg
- 15.7mg
- 18.8mg
extended-release oral suspension (Adzenys ER): Schedule II
- 1.25 mg/mL
Narcolepsy
5-60 mg/day PO in divided doses depending on the individual patient response
Administer at the lowest effective dose; individually adjust dosage
Obesity
Indicated as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy (eg, repeated diets, group programs, and other drugs)
Usual dosage is up to 30 mg daily, taken in divided doses of 5-10 mg, 30-60 minutes before meals
Administer at the lowest effective dose; individually adjust dosage
Attention Deficit Hyperactivity Disorder
Indicated for attention deficit hyperactivity disorder (ADHD) in adolescents and adults
Adzenys XR-ODT: 12.5 mg PO qAM
Adzenys ER: 12.5 mg PO qAM
Dyanavel XR: 2.5-5 mg PO qAM; may increase by 2.5 -10 mg/day q4-7days; not to exceed 20 mg/day
Evekeo: 5 mg PO qDay or q12hr; may increase by 5 mg qWeek until optimal response is obtained; not to exceed 40 mg/day
Dosage Modifications
Equivalent doses of Adzenys ER or Adzenys XR-ODT and Adderall XR
- Adzenys ER/XR-ODT 3.1 mg (2.5 mL): Adderall XR 5 mg
- Adzenys ER/XR-ODT 6.3 mg (5 mL): Adderall XR 10 mg
- Adzenys ER/XR-ODT 9.4 mg (7.5mL): Adderall XR 15 mg
- Adzenys ER/XR-ODT 12.5 mg (10 mL): Adderall XR 20 mg
- Adzenys ER/XR-ODT 15.7 mg (12.5 mL): Adderall XR 25 mg
- Adzenys ER/XR-ODT 18.8 mg (15 mL): Adderall XR 30 mg
Concomitant use of extended-release amphetamines with other medications
- Do not administer concomitantly or within 14 days after discontinuing MAO inhibitors
- Coadministration of and gastrointestinal alkalinizing agents should be avoided
- See Warnings
Dosing Considerations
Do not substitute for other amphetamine products on a mg-per-mg basis, because of different amphetamine base compositions and differing pharmacokinetic profiles
Before initiating
- Assess for presence of cardiac disease (ie, perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam)
- Assess risk of abuse before prescribing, and monitor for signs of abuse and dependence while on therapy; maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically re-evaluate the need for use
Dosage Forms & Strengths
tablet (Evekeo): Schedule II
- 5mg
- 10mg
oral disintegrating tablet (Evekeo ODT): Schedule II
- 5mg
- 10mg
- 15mg
- 20mg
extended-release oral tablets (Dyanavel XR): Schedule II
- 5mg
- 10mg
- 15mg
- 20mg
extended-release oral suspension (Dyanavel XR): Schedule II
- 2.5mg/mL
extended-release oral disintegrating tablet (Adzenys XR-ODT): Schedule II
- 3.1mg
- 6.3mg
- 9.4mg
- 12.5mg
- 15.7mg
- 18.8mg
extended-release oral suspension (Adzenys ER): Schedule II
- 1.25 mg/mL
Attention Deficit Hyperactivity Disorder
Evekeo
- <3 years: Safety and efficacy not established
- 3-5 years: 2.5 mg PO qDay initially; may increase daily dose by 2.5-mg increments at weekly intervals until optimal response is obtained
- ≥6 years: 5 mg PO qDay initially; may increase daily dose by 5-mg increments at weekly intervals until optimal response is obtained; only in rare cases will it be necessary to exceed 40 mg/day
- If necessary, administer additional doses (1-2) at intervals of 4-6 hr
Evekeo ODT
- <3 years: Safety and efficacy not established
- 3-5 years: 2.5 mg PO qDay; if needed, may increase daily dose at weekly intervals by 2.5 mg depending on response and tolerability
- 6-17 years: 5 mg PO qDay; if needed, may increase daily dose at weekly intervals by 2.5-5 mg until optimal response obtained
- If necessary, administer an additional dose after 4-6 hr
- Only in rare cases will it be necessary to exceed 40 mg/day
- Where possible, interrupt drug administration occasionally to determine if behavioral symptoms recur and are sufficient to require continued therapy
- Administer at lowest effective dose and individually adjust
Dyanavel XR
- <6 years: Safety and efficacy not established
- ≥6 years: Initial: 2.5-5 mg PO qAM
- May increase dose in increments of 2.5-10 mg/day q4-7 days; not to exceed dose of 20 mg/day
Adzenys XR-ODT or Adzenys ER
- <6 years: Safety and efficacy not established
- 6-17 years (initial dose): 6.3 mg PO qDay in AM; not to exceed 18.8 mg/day (6-12 years); 12.5 mg/day (13-17 years)
Narcolepsy (Evekeo)
Seldom occurs in children younger than 12 yr; however, when it does, amphetamine may be prescribed
6-12 years: 5 mg/day PO initially; daily dose may be increased by 5-mg increments at weekly intervals until optimal response obtained
≥12 years: 10 mg/day PO initially; daily dose may increase by 10-mg increments at weekly intervals until optimal response is obtained
Administer in divided doses according to individual response
Administer first dose on awakening; give additional doses (5-10 mg) at intervals of 4-6 hr
Obesity (Evekeo)
Indicated as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy (eg, repeated diets, group programs, and other drugs)
<12 years: Safety and efficacy not established
≥12 years: Usual dosage is up to 30 mg daily, taken in divided doses of 5-10 mg, 30-60 minutes before meals
Dosage Modifications
Agents that alter urinary pH can impact urinary excretion and alter blood levels of amphetamine
Acidifying agents (eg, ascorbic acid) decrease blood levels, while alkalinizing agents (eg, sodium bicarbonate) increase blood levels; adjust dosage accordingly
Dosing Considerations
Before initiating
- Assess for the presence of cardiac disease (ie, perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam)
- Assess risk of abuse before prescribing, and monitor for signs of abuse and dependence while on therapy; maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically re-evaluate the need for use
Switching From Other Amphetamine Products
- Do not substitute for other amphetamine products on a mg-per-mg basis, because of different amphetamine base compositions and differing pharmacokinetic profiles
- Switching from Evekeo to Evekeo ODT can done on a mg-per-mg basis
- Switching from other amphetamine products to Evekeo ODT, discontinue treatment and titrate with Evekeo ODT using the titration schedule above
- May substitute Dyanavel XR extended-release oral suspension with Dyanavel XR extended-release tablets on a mg-per-mg basis
- Avoid late evening doses because of insomnia
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (2)
- iobenguane I 131
amphetamine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
- ozanimod
ozanimod increases toxicity of amphetamine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
Monitor Closely (8)
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, amphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
- buprenorphine, long-acting injection
amphetamine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
- dextromethorphan
amphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .
- epinephrine inhaled
amphetamine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, amphetamine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- hydrocodone
hydrocodone, amphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
- sodium zirconium cyclosilicate
sodium zirconium cyclosilicate will increase the level or effect of amphetamine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate. Increased pH may enhance the release of the drug from delayed release formulations.
- sufentanil SL
sufentanil SL, amphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
Minor (0)
Adverse Effects
>10% (Evekeo)
Decreased appetite (28%)
Infections (22%)
Abdominal pain (15%)
Irritability (14%)
Headache (13%)
>10% (Adzenys ER)
Appetite loss (22-36%)
Dry mouth (1.6-35%)
Headache (1.6-26%)
Insomnia (5.2-17%)
Abdominal pain (11-14%)
1-10% (Evekeo)
Insomnia (10%)
Fatigue (10%)
Affect lability, includes mood swings (9%)
Tachycardia (9%)
Nausea (6%)
Vomiting (6%)
Dry mouth (6%)
Decreased appetite (4%)
Insomnia (4%)
Abdominal pain (3%)
Affect lability (3%)
Injury (3%)
1-10% (Dyanavel XR)
Epistaxis (3.8%)
Rhinitis allergic (3.8%)
Upper abdominal pain (3.8%)
1-10% (Adzenys ER)
Weight loss (4-9%)
Emotional lability (9%)
Nausea (5-8%)
Agitation (8%)
Anxiety (2.1-8%)
Dizziness (2-7%)
Vomiting (7%)
Diarrhea (6%)
Nervousness (6%)
Urinary tract infection (5%)
Fever (5%)
Infection (4%)
Accidental injury (3%)
Asthenia (1-2%)
Dyspepsia (2%)
Nervousness (1.6%)
Tachycardia (1.6%)
Postmarketing Reports
Cardiovascular: Palpitations, tachycardia, sudden death, myocardial infarction; elevation of blood pressure; isolated reports of cardiomyopathy associated with chronic use
Central nervous system: Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, depression, aggression, anger, logorrhea, and paresthesia (including formication). euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and phonic tics and Tourette’s syndrome
Gastrointestinal: Dry mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia, anorexia, and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect
Allergic: Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported
Endocrine: Impotence, changes in libido, and frequent or prolonged erections
Skin: Alopecia
Eye Disorders: Vision blurred, mydriasis
Vascular disorders: Raynaud phenomenon
Musculoskeletal: Rhabdomyolysis
Warnings
Black Box Warnings
Abuse and dependence
- CNS stimulants, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence
- Assess risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy
Contraindications
Advanced arteriosclerosis, symptomatic cardiovascular disease, or moderate-to-severe hypertension
In patients known to be hypersensitive to amphetamine, or other components
Patients with a history of drug abuse
During or within 14 days following the administration of MAOIs (hypertensive crises may result)
Cautions
Sudden death reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems
May cause a modest increase in average blood pressure (~2-4 mmHg) and heart rate (~3-6 bpm); caution with hypertension and other cardiovascular conditions
May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder CNS stimulants may induce a mixed or manic episode in patients with bipolar disorder; before initiating treatment, screen for risk factors for developing a manic episode (eg, comorbid or has a history of depressive symptoms or a family history of suicide, bipolar disorder, and depression)
Treatment emergent psychotic or manic symptoms (eg, hallucinations, delusional thinking, mania) in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses
Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD; monitor for the worsening of aggressive behavior or hostility
Monitor childhood growth during treatment; patients who are not growing or gaining height or weight as expected may need to interrupt their treatment
May lower seizure threshold in patients with prior history of seizures
Stimulants are associated with peripheral vasculopathy, including Raynaud phenomenon
Visual disturbances reported (eg, difficulties with accommodation, blurred vision)
Medication errors, including substitution and dispensing errors, between amphetamine products could occur, leading to possible overdosage; avoid substitution errors and overdosage, do not substitute for other amphetamine products on a mg-per-mg basis because of different amphetamine salt compositions and differing pharmacokinetic profile
Drug interactions overview
- Amphetamines can cause a significant elevation in plasma corticosteroid levels (greatest increase in the evening); may interfere with urinary steroid determinations
- Concomitant use of amphetamines with alkalizing agents (eg, proton pump inhibitors) may increase exposure to amphetamine and exacerbate the action of amphetamine
- Coadministration with acidifying agents (eg, ascorbic acid) may lower blood levels and efficacy of amphetamines
- Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort
- Amphetamines are metabolized by CYP2D6 and minor iCYP2D6 inhibitors; coadministration with CYP2D6 inhibitors may increase exposure to amphetamines; consider alternative non-serotonergic drug or alternative drug that does not inhibit CYP2D6
- If concomitant use with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate therapy with lower doses, monitor for emergence of serotonin syndrome during drug initiation or titration, and inform patients of increased risk for serotonin syndrome
Pregnancy & Lactation
Pregnancy
Pregnancy exposure registry monitors pregnancy outcomes in women exposed to amphetamines during pregnancy
Encourage patients to register by calling the National Pregnancy Registry for Psychostimulants at 1-866- 961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications
Available data from published epidemiologic studies and postmarketing reports on use of prescription amphetamine in pregnant women have not identified a drug-associated risk of major birth defects and miscarriage
Adverse pregnancy outcomes, including premature delivery and low birth weight, were seen in infants born to mothers taking amphetamines during pregnancy
Dextroamphetamine sulfate shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses ~41 times the maximum human dose
Clinical considerations
- Amphetamines cause vasoconstriction and thereby decrease placental perfusion
- Also, may stimulate uterine contractions, increasing the risk of premature delivery
- Infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight; monitor infants born to mothers taking amphetamines for symptoms of withdrawal (eg, feeding difficulties, irritability, agitation, excessive drowsiness)
Animal data
- No effects on morphological development observed in embryo-fetal development studies with oral administration of amphetamine to rats and rabbits during organogenesis at doses that are approximately 3 and 16 times, respectively, the maximum recommended human dose (MRHD) of 20 mg/day (as base equivalents) on mg/m2 basis, given to adults
- However, long-term neurochemical and behavioral effects have been reported in published animal developmental studies using clinically relevant doses of amphetamine
Lactation
Based on limited published case reports, amphetamine (d- or d1) is present in human milk at relative infant doses of 2-13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9and 7.5
No reports of adverse effects on the breastfed infantLong-term neurodevelopmental effects on infants from amphetamine exposure are unknown
Owing to the potential for serious adverse reactions in nursing infants, breast feeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Noncatecholamine, sympathomimetic amine that elicits CNS stimulant activity
Peripheral actions include increased systolic and diastolic blood pressures, and weak bronchodilator and respiratory stimulant action
Absorption
Adzenys XR-ODT
- Peak plasma time, d-amphetamine: 5 hr (fasted); 7 hr (fed)
- Peak plasma concentration, d-amphetamine: 44.9 ng/mL (fasted); 36.3 ng/mL (fed)
- AUC, d-amphetamine: 876.9 hr·ng/mL (fasted); 856.3 hr·ng/mL (fed)
- Coadministration of Adzenys XR-ODT and food prolonged peak plasma time by ~2 hr (d-amphetamine); 2.5 hr (l-amphetamine)
Adzenys ER
- Peak plasma time: 5 hr
- Increase in amphetamine release occurred in the presence of 40% alcohol
Dyanavel XR
- Peak plasma time: 4 hr
- Bioavailability of Dyanavel XR compared to an equal dose of mixed amphetamine salts IR tablets is 106% (d-amphetamine) and 111% (l-amphetamine)
Evekeo ODT
- Peak plasma time (Evekeo ODT [d- and l-amphetamine]): ~3.5 hr (with water) and 3 hr (without water)
Metabolism
Amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated
In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amphetamine and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites
Elimination
Adzenys ER
- Half-life, d-amphetamine: 11.4 hr (adults); 12.7 hr (6-12 years)
- Half-life, l-amphetamine: 14.1 hr (adults); 15.3 hr (6-12 years)
- Excretion: Urine (30-40%)
Adzenys XR-ODT
- Half-life, d-amphetamine: 11 hr (adults); 9-10 hr (6-12 years)
- Half-life, l-amphetamine: 14 hr (adults); 10-11 hr (6-12 years)
- Excretion: Urine (30-40%)
Dyanavel XR
- Half-life, d-amphetamine: 12.36 hr (adults)
- Half-life, l-amphetamine: 15.12 hr (adults)
- Excretion: Urine (30-40%)
Evekeo ODT
- Half-life (Evekeo ODT): 10 hr (d-amphetamine); 11.7 hr (l-amphetamine)
- Renally eliminated in a pH-dependent mannerRenal excretion rate of unchanged amphetamine at a urine pH= 6.6 averages 70% versus 17%; - 43% at urine pH of >6.7
Administration
Oral Administration
Avoid late evening doses because of insomnia
Tablet
- Take 30-60 minutes before meals
- Administer first dose on awakening; 1-2 additional doses at 4-6 hr intervals
Oral suspension
Shake suspension well before measuring dose with a calibrated measuring device
Take with or without meals
-
Dyanavel XR
- Firmly insert the bottle adapter into the bottle and do not remove once inserted
- Use oral dosing dispenser provided by pharmacist
Oral disintegrating tablet
- May be taken with or without food
- Once blister is opened, remove tablet and place on patient’s tongue
- Place whole tablet on the tongue and allow tablet to disintegrate in saliva then swallow
Extended-release tablets
- Chew or swallow whole
- May divide 5 mg extended-release tablet into equal halves (2.5 mg) at the score line
Storage
Evekeo: Store at 20-25°C (68-77°F); dispense in a well closed container
Evekeo ODT: Store at 20-25°C (68- 77°F); excursions permitted from 15-30ºC (59-86ºF); store blister packages in the provided plastic sleeve
Dyanavel XR: Dispense in a tight container with child resistant closure; store at 20-25°C (68- 77°F); excursions permitted from 15-30ºC (59-86ºF)
Adzenys XR-ODT: Store blister packages in the rigid, plastic travel case provided after removal from the carton; store at 20-25°C (68- 77°F); excursions permitted from 15-30ºC (59-86ºF)
Adzenys ER: Dispense in a tight container with child-resistant closure; store at 20-25°C (68- 77°F); excursions permitted from 15-30ºC (59-86ºF)
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Formulary
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