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

Difficulties with accommodation and blurring of vision reported with stimulant treatment.

Methamphetamine should not be used to combat fatigue or to replace rest in normal persons

Prescribing and dispensing of methamphetamine should be limited to smallest amount that is feasible at one time in order to minimize possibility of overdosage.

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 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

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; use caution

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

Consistently methylphenidate medicated children (ie, treatment for 7 days per week throughout the year) have a temporary slowing in growth rate; published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, it is anticipated that they likely have this effect; monitor growth during treatment with stimulants; patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted

Serotonin syndrome

• Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems
• Symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)
• Discontinue treatment if above symptoms occur, and initiate supportive symptomatic treatment; 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

Peripheral vasculopathy

• Stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon; signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown
• Effects of peripheral vasculopathy, including Raynaud’s phenomenon, observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment
• Signs and symptoms generally improve after reduction in dose or discontinuation of drug; careful observation for digital changes is necessary during treatment with ADHD stimulants; further clinical evaluation (eg, rheumatology referral) may be appropriate for certain patients

Cardiovascular events

• 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
• Sudden death has been reported in association with CNS stimulant treatment at usual doses in patients with structural cardiac abnormalities or other serious heart problems
• Not for use in children, adolescents or adults with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug
• Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may have larger increases
• All patients should be monitored for larger changes in heart rate and blood pressure; caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, eg, those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia
• Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (eg, electrocardiogram and echocardiogram)
• 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

Psychiatric effects

• Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder
• 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
• Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
• Treatment-emergent psychotic or manic symptoms, eg, hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses; if such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate
• 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; although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for appearance of or worsening of aggressive behavior or hostility

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