methamphetamine (Rx)

Frequency Not Defined

Common

• Hypertension, palpitations, tachyarrhythmia
• Dizziness, drug tolerance, dysphoric mood, euphoria, headache, insomnia, restlessness, tremor
• Urticaria
• Constipation, diarrhea, taste sense altered, xerostomia

Serious

• Cardiorespiratory arrest, sudden death (rare), myocardial infarction
• Cerebrovascular accident, Gilles de la Tourette's syndrome, seizure, psychotic disorder
• Also see sympathomimetic syndrome, amphetamine toxicity
• Musculoskeletal: Rhabdomyolysis

Postmarketing Reports

Alopecia

Contraindications

Within 14 days of MAOIs

Advanced arteriosclerosis

Symptomatic cardiovascular disease

Hyperthyroidism

Moderate-severe hypertension

Hypersensitivity to sympathomimetic amines

Glaucoma

Agitated state

History of drug abuse

Patients with ADHD concomitant with Tourette's syndrome

Breastfeeding

Cautions

Bipolar disorder, mild hypertension, history of seizures, diabetes (insulin requirement may be altered), history of aggressive behavior

Do not give at late evening; may cause insomnia

May impair ability to drive and/or operate heavy machinery

Alkaline urine will significantly increase half-life

Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon

Sudden deaths, stroke, and myocardial infarction reported in adults taking stimulants at usual doses

Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation

Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients

Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility

Monitor growth of children ages 7 to 10 years during treatment with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected

Stimulants may lower convulsive threshold in patients with prior history of seizure, patients with prior EEG abnormalities in absence of seizures, and very rarely, patients without a history of seizures and no prior EEG evidence of seizures; discontinue therapy in the presence of seizures

Use with caution in patients who use other sympathomimetic drugs

Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome; perform clinical evaluation for tics and Tourette’s syndrome in children and their families prior to treating with stimulant medications

High abuse potential

Rare instances of prolonged and sometimes painful erections (priapism), sometimes requiring surgical intervention, reported with methylphenidate products; typically not reported during initiation, but often subsequent to an increase in dose; seek immediate medical attention for abnormally sustained or frequent and painful erections

Drug interaction overview

• 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 known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism; potential for a pharmacokinetic interaction exists with coadministration of CYP2D6 inhibitors which may increase risk with increased exposure to amphetamines; in these situations, 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 patients for emergence of serotonin syndrome during drug initiation or titration, and inform patients of increased risk for serotonin syndrome

Pregnancy Category: C

Lactation: do not nurse

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.

Mechanism of Action

Amphetamine anorexigenic agent; sympathomimetic amine related to ephedrine and amphetamine with CNS stimulant activity; causes release of dopamine and other catechoamines from their storage in the presynaptic nerve terminals; inhibits monoamine transporters and oxidase, causing reuptake and metabolism of catecholamines

Pharmacokinetics

Half-Life: 4-5 hr

Absorption: Rapid

Metabolism: Liver

Excretion: Urine, varies with pH