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Amphetamine

Pronunciation

Pronunciation

(am FET a meen)

Index Terms

  • Amphetamine Sulfate
  • Racemic Amphetamine Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Extended Release, Oral, as base:

Dyanavel XR: 2.5 mg/mL (464 mL) [contains methylparaben, polysorbate 80, propylparaben]

Tablet, Oral, as sulfate:

Evekeo: 5 mg [scored]

Evekeo: 10 mg [scored; contains brilliant blue fcf (fd&c blue #1)]

Tablet Extended Release Dispersible, Oral, as base:

Adzenys XR-ODT: 3.1 mg, 6.3 mg, 9.4 mg, 12.5 mg, 15.7 mg, 18.8 mg

Brand Names: U.S.

  • Adzenys XR-ODT
  • Dyanavel XR
  • Evekeo

Pharmacologic Category

  • Central Nervous System Stimulant

Pharmacology

Amphetamines are noncatecholamine sympathomimetic amines that promote release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals. A less significant mechanism may include their ability to block the reuptake of catecholamines by competitive inhibition. The anorexigenic effect is probably secondary to the CNS-stimulating effect; the site of action is probably the hypothalamic feeding center.

Absorption

Oral: Evekeo: Rapid (de la Torre 2004)

Distribution

Oral: Evekeo: Vd: 3 to 4 L/kg (de la Torre 2004)

Metabolism

Hepatic via oxidation, deamination, and CYP2D6

Excretion

Urine (30% to 40%)

Time to Peak

Oral:

Adzenys XR-ODT: Median time d-amphetamine 5 hours (7 hours with food) and l-amphetamine 5.25 hours (7.75 hours with food)

Dyanavel XR:

Children: Median time d-amphetamine 3.9 hours and l-amphetamine 4.5 hours

Adults: 4 (2 to 7) hours

Evekeo: Serum: Within 4 hours (de la Torre 2004)

Half-Life Elimination

Oral:

Adzenys XR-ODT:

Children 6 to 12 years: d-amphetamine 9 to 10 hours (mean) and l-amphetamine 10 to 11 hours (mean)

Adults: d-amphetamine 11 hours (mean) and l-amphetamine 14 hours (mean)

Dyanavel XR:

Children: d-amphetamine 10.43 ± 2.01 hours and l-amphetamine 12.14 ± 3.15 hours

Adults: d-amphetamine 12.36 ± 2.95 hours and l-amphetamine 15.12 ± 4.4 hours

Evekeo: 12 hours (de la Torre 2004)

Protein Binding

Oral: Evekeo: 16% (de la Torre 2004)

Special Populations Note

Body weight: Systemic exposure and maximum concentration of d- and l-amphetamine decrease as body weight increases; volume of distribution, clearance and half-life increase as body weight increases.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder : Treatment of attention-deficit/hyperactivity disorder (ADHD)

Exogenous obesity (immediate release tablet only): Short-term treatment of exogenous obesity as an adjunct to caloric restriction for patients refractory to alternative therapy (eg, repeated diets, group programs, and other drugs).

Narcolepsy (immediate release tablet only): Treatment of narcolepsy.

Contraindications

Immediate release: Hypersensitivity or idiosyncrasy to amphetamine or other sympathomimetic amines; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; hyperthyroidism; agitated states; history of drug abuse; use during or within 14 days following MAO inhibitor.

Extended release: Hypersensitivity to amphetamine or any component of the formulation, anaphylactic reactions and angioedema have been reported; use during or within 14 days following MAO inhibitor.

Documentation of allergenic cross-reactivity for amphetamines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Administer at the lowest effective dose.

Attention deficit/hyperactivity disorder:

Extended-release orally disintegrating tablet: Oral: 12.5 mg once daily.

Conversion: Do not substitute extended-release formulation for other amphetamine formulations on a mg-per-mg basis

Converting from Adderall XR to Adzenys XR-ODT: Initial dose of Adzenys XR-ODT should be determined by the current dose of Adderall XR as follows:

Current Adderall XR dose of 5 mg once daily: Initial Adzenys XR-ODT dose of 3.1 mg once daily

Current Adderall XR dose of 10 mg once daily: Initial Adzenys XR-ODT dose of 6.3 mg once daily

Current Adderall XR dose of 15 mg once daily: Initial Adzenys XR-ODT dose of 9.4 mg once daily

Current Adderall XR dose of 20 mg once daily: Initial Adzenys XR-ODT dose of 12.5 mg once daily

Current Adderall XR dose of 25 mg once daily: Initial Adzenys XR-ODT dose of 15.7 mg once daily

Current Adderall XR dose of 30 mg once daily: Initial Adzenys XR-ODT dose of 18.8 mg once daily

Converting from all other amphetamine formulations to Adzenys XR-ODT: Discontinue that treatment and titrate Adzenys XR-ODT as per the recommended dosing schedule.

Extended-release suspension: Oral: Initial: 2.5 or 5 mg once daily; may increase in 2.5 to 10 mg/day increments every 4 to 7 days until optimal response is obtained (maximum: 20 mg/day)

Note: Do not substitute extended-release formulation for other amphetamine products on a mg-per-mg basis since base composition and pharmacokinetic profiles are not similar. If switching from other amphetamine products, discontinue that treatment, and titrate as per the recommended dosing schedule.

Exogenous obesity: Immediate-release tablet: Oral: Up to 30 mg daily in divided doses (5 to 10 mg per dose)

Narcolepsy: Immediate-release tablet: Oral: Initial: 10 mg once daily; increase daily dose in 10 mg increments at weekly intervals until optimal response is obtained; usual dosage range: 5 to 60 mg daily in divided doses

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Administer at the lowest effective dose.

Attention deficit/hyperactivity disorder:

Extended-release orally disintegrating tablet:

Children ≥6 years: Oral: Initial: 6.3 mg once daily; may increase in 3.1 mg or 6.3 mg increments every week until optimal response is obtained (maximum: 6 to 12 years: 18.8 mg/day)

Adolescents: Oral: Initial: 6.3 mg once daily; may increase in 3.1 mg or 6.3 mg increments every week until optimal response is obtained (maximum: 12.5 mg/day)

Conversion: Note: Do not substitute extended-release formulation for other amphetamine formulations on a mg-per-mg basis

Converting from Adderall XR to Adzenys XR-ODT: Initial dose of Adzenys XR-ODT should be determined by the current dose of Adderall XR as follows:

Current Adderall XR dose of 5 mg once daily: Initial Adzenys XR-ODT dose of 3.1 mg once daily

Current Adderall XR dose of 10 mg once daily: Initial Adzenys XR-ODT dose of 6.3 mg once daily

Current Adderall XR dose of 15 mg once daily: Initial Adzenys XR-ODT dose of 9.4 mg once daily

Current Adderall XR dose of 20 mg once daily: Initial Adzenys XR-ODT dose of 12.5 mg once daily

Current Adderall XR dose of 25 mg once daily: Initial Adzenys XR-ODT dose of 15.7 mg once daily

Current Adderall XR dose of 30 mg once daily: Initial Adzenys XR-ODT dose of 18.8 mg once daily

Converting from all other amphetamine formulations to Adzenys XR-ODT: Discontinue that treatment and titrate Adzenys XR-ODT as per the recommended dosing schedule.

Extended-release suspension: Children ≥6 years and Adolescents: Oral: Refer to adult dosing.

Immediate-release tablet:

Children 3 to 5 years: Oral: Initial: 2.5 mg once daily; increase daily dose in 2.5 mg increments at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed 40 mg daily.

Children ≥6 years and Adolescents: Oral: Initial: 5 mg once or twice daily; increase daily dose in 5 mg increments at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed 40 mg daily.

Exogenous obesity: Immediate-release tablet: Children ≥12 years and Adolescents: Oral: Up to 30 mg daily in divided doses (5 to 10 mg per dose)

Narcolepsy: Immediate-release tablet:

Children 6 to 12 years: Oral: Initial: 5 mg once daily; increase daily dose in 5 mg increments at weekly intervals until optimal response is obtained; usual dosage range: 5 to 60 mg daily in divided doses

Children ≥12 years and Adolescents: Oral: Initial: 10 mg once daily; increase daily dose in 10 mg increments at weekly intervals until optimal response is obtained; usual dosage range: 5 to 60 mg daily in divided doses

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Administration

Oral:

Extended-release orally disintegrating tablet: Administer in the morning with or without food. Do not remove from blister until ready to administer. Using dry hands, peel backing off the blister; do not push tablet through foil. Remove tablet and immediately place on tongue and allow to disintegrate. Swallow with saliva. Do not chew or crush tablet.

Extended-release suspension: Administer in the morning with or without food; use an oral dosing syringe or other suitable measuring device when dosing suspension. Shake bottle well prior to administration.

Immediate-release tablet: Administer with or without food; for short-term adjunct treatment of exogenous obesity, administer 30 to 60 minutes before meals. Administer the first dose on awakening; administer additional doses at intervals of 4 to 6 hours. Avoid late evening dosing.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF). Store orally disintegrating tablet blister packages in travel case provided.

Drug Interactions

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Alkalinizing Agents: May decrease the excretion of Amphetamines. Consider therapy modification

Ammonium Chloride: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Analgesics (Opioid): Amphetamines may enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Antacids: May decrease the excretion of Amphetamines. Monitor therapy

Antihistamines: Amphetamines may diminish the sedative effect of Antihistamines. Monitor therapy

Antihypertensive Agents: Amphetamines may diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents: May diminish the stimulatory effect of Amphetamines. Monitor therapy

Ascorbic Acid: May decrease the serum concentration of Amphetamines. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of Amphetamines. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ethosuximide: Amphetamines may diminish the therapeutic effect of Ethosuximide. Amphetamines may decrease the serum concentration of Ethosuximide. Monitor therapy

Gastrointestinal Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Amphetamines may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Lithium: May diminish the stimulatory effect of Amphetamines. Monitor therapy

MAO Inhibitors: May enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Tedizolid. Avoid combination

Methenamine: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Multivitamins/Fluoride (with ADE): May decrease the serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Amphetamines. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Monitor therapy

PHENobarbital: Amphetamines may decrease the serum concentration of PHENobarbital. Monitor therapy

Phenytoin: Amphetamines may decrease the serum concentration of Phenytoin. Monitor therapy

Proton Pump Inhibitors: May increase the absorption of Amphetamine. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

Urinary Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy

Test Interactions

Amphetamines may elevate plasma corticosteroid levels; may interfere with urinary steroid determinations.

Adverse Reactions

As reported in children and adults unless otherwise noted.

>10%:

Central nervous system: Insomnia (12% to 27%), headache (26%: adult)

Gastrointestinal: Anorexia (22% to 36%: dose related), xerostomia (35%: adult), abdominal pain (11% to 14%)

1% to 10%:

Cardiovascular: Tachycardia (6%), palpitations (2% to 4%)

Central nervous system: Emotional lability (2% to 9%), agitation (8%), anxiety (8%), dizziness (2% to 7%), nervousness (6%), drowsiness (2% to 4%), speech disturbance (2% to 4%), twitching (2% to 4%)

Dermatologic: Hyperhidrosis (2% to 4%), skin photosensitivity (2% to 4%)

Endocrine & metabolic: Loss of libido (2% to 4%)

Gastrointestinal: Weight loss (4% to 10%: dose related), nausea (5% to 8%), vomiting (7%), diarrhea (6%), upper abdominal pain (children: 4%), constipation (2% to 4%), dental disease (2% to 4%), dyspepsia (2%)

Genitourinary: Urinary tract infection (5%), dysmenorrhea (2% to 4%), impotence (2% to 4%), tooth infection (2% to 4%; including tooth disorder and teeth clenching)

Infection: Infection (2% to 4%)

Neuromuscular & skeletal: Weakness (2% to 6%)

Respiratory: Allergic rhinitis (children: 4%), epistaxis (children: 4%), dyspnea (2% to 4%)

Miscellaneous: Fever (5%), accidental injury (3%)

Frequency not defined:

Cardiovascular: Cardiomyopathy (chronic), increased blood pressure

Central nervous system: Dysphoria, euphoria, exacerbation of Gilles de la Tourette's syndrome, exacerbation of tics, exacerbation of vocal tics, overstimulation, restlessness

Dermatologic: Urticaria

Endocrine & metabolic: Change in libido

Gastrointestinal: Dysgeusia, gastrointestinal distress

Genitourinary: Frequent erections, priapism

Neuromuscular & skeletal: Dyskinesia, tremor

<1% (Limited to important or life-threatening): Cardiomyopathy (with chronic use), peripheral vascular disease, psychosis (including delusions, hallucination, and mania in children and adolescents), Raynaud's phenomenon

ALERT: U.S. Boxed Warning

Abuse potential (Adzenys XR-ODT, Dyanavel XR, Evekeo):

Amphetamines have a high potential for abuse and dependence. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly.

Cardiovascular events (Evekeo):

Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: [US Boxed Warning; Immediate release]: Misuse may cause serious cardiovascular events including sudden death. Adverse effects have been reported at usual doses in patients with preexisting structural cardiac abnormalities or other serious heart problems (sudden death in children and adolescents; sudden death, stroke, and MI in adults). These products should be avoided in the patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during treatment should undergo a prompt cardiac evaluation.

• CNS effects: May impair the ability to engage in potentially hazardous activities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hypersensitivity: Angioedema and anaphylactic reactions have been reported.

• Hypertension/tachycardia: May occur; monitor blood pressure and heart rate in all patients.

• Peripheral vasculopathy: Stimulants are associated with peripheral vasculopathy, including Raynaud phenomenon; signs/symptoms are usually mild and intermittent, and generally improve with dose reduction or discontinuation. Digital ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during therapy and seek further evaluation (eg, rheumatology) if necessary (Syed, 2008).

• Visual disturbance: Difficulty in accommodation and blurred vision has been reported with the use of stimulants.

Disease-related concerns:

• Abuse potential: [US Boxed Warning]: Potential for drug abuse and dependency exists; prolonged use may lead to drug dependency and must be avoided. Assess the risk for abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Consider the possibility of patients obtaining amphetamines for non-therapeutic use or distribution to others; prescribe sparingly. Use of immediate-release formulation is contraindicated in patients with history of drug abuse. Write prescriptions for the smallest quantity consistent with good patient care to minimize possibility of overdose.

• Cardiovascular disease: Use with caution in patients with hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate (eg, pre-existing hypertension, heart failure, recent myocardial infarction, ventricular arrhythmia). Use of immediate-release formulation is contraindicated in patients with advanced arteriosclerosis, moderate to severe hypertension, or symptomatic cardiovascular disease.

• Psychiatric disorders: Use with caution in patients with preexisting psychosis or bipolar disorder; may exacerbate symptoms of behavior and thought disorder or induce mixed/manic episode, respectively. Screen patients with comorbid depressive symptoms prior to initiating treatment to determine if they are at risk for bipolar disorder, including a family history of suicide, bipolar disorder, and depression. May be associated with aggressive behavior or hostility (causal relationship not established); monitor for development or worsening of these behaviors. New-onset psychosis or mania may also occur with stimulant use; consider discontinuing therapy if hallucinations, delusional thinking or mania occurs.

• Seizure disorder: Limited information exists regarding amphetamine use in seizure disorder (Cortese, 2013). Use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity.

• Tourette syndrome/Tics: Use with caution in patients with Tourette syndrome or other tic disorders. Stimulants may exacerbate tics (motor and phonic) and Tourette syndrome; however, evidence demonstrating increased tics is limited. Evaluate for tics and Tourette syndrome prior to therapy initiation (AACAP [Murphy 2013]; Pliszka 2007).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Appetite suppression may occur; monitor weight during therapy. Use of stimulants has been associated with weight loss and slowing of growth rate; monitor growth rate and weight during treatment. Treatment interruption may be necessary in patients who are not increasing in height or gaining weight as expected.

Other warnings/precautions:

• Discontinuation of therapy: Abrupt discontinuation following high doses or for prolonged periods may result in symptoms for withdrawal.

Monitoring Parameters

Blood pressure, pulse; height and weight in children

When used for the treatment of ADHD, perform a targeted cardiac history (eg, patient history of previously detected cardiac disease, palpitations, syncope, or seizures; family history of sudden death in children or young adults; hypertrophic cardiomyopathy; long QT syndrome) and physician examination including cardiac examination. Monitor heart rate and blood pressure (baseline; follow-up within 1 to 3 months and routinely at 6 to 12 month intervals thereafter unless clinically indicated with dose titration and weaning of therapy) Consider obtaining ECG prior to initiation (Perrin, 2008; Vetter, 2008).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse effects have been observed in animal reproduction studies. The majority of human data are based on illicit amphetamine/methamphetamine exposure and not from therapeutic maternal use (Golub, 2005). Use of amphetamines during pregnancy may lead to an increased risk of premature birth and low birth weight; newborns may experience symptoms of withdrawal. Behavioral problems may also occur later in childhood (LaGasse, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dry mouth, lack of appetite, insomnia, constipation, weight loss, nausea, diarrhea, bad taste in mouth, abdominal pain, or agitation. Have patient report immediately to prescriber tachycardia, abnormal heartbeat, severe anxiety, severe headache, tremors, vision changes, seizure, abnormal movements, sores on fingers or toes, skin discoloration, burning or numbness feeling, sexual dysfunction, decreased libido, priapism, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of breathing problems (shortness of breath, wheezing, coughing, or breathing gets worse), angina, severe dizziness, passing out, signs of severe mood and behavioral changes, or signs of depression (suicidal ideation, anxiety, emotional instability, or confusion) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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