Methamphetamine

Pronunciation

(meth am FET a meen)

U.S. Brand Names

Desoxyn®

Synonyms

Desoxyephedrine Hydrochloride; Methamphetamine Hydrochloride

Generic Available

Yes

Canadian Brand Names

Desoxyn®

Use

Treatment of attention-deficit/hyperactivity disorder (ADHD); exogenous obesity (short-term adjunct)

Use - Unlabeled/Investigational

Narcolepsy

Restrictions

C-II

Pregnancy Risk Factor

Lactation

Enters breast milk/contraindicated

Contraindications

Hypersensitivity or idiosyncrasy to amphetamines or other sympathomimetic amines; patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension (stage II or III), hyperthyroidism, glaucoma, agitated states; patients with a history of drug abuse; use during or within 14 days following MAO inhibitor therapy; stimulant medications are contraindicated for use in children with attention-deficit/hyperactivity disorders and concomitant Tourette's syndrome or tics

Warnings/Precautions

Use with caution in patients with bipolar disorder, diabetes mellitus, cardiovascular disease, seizure disorders, insomnia, porphyria, or mild hypertension (stage I). May exacerbate symptoms of behavior and thought disorder in psychotic patients. Potential for drug dependency exists - avoid abrupt discontinuation in patients who have received for prolonged periods. Use in weight reduction programs only when alternative therapy has been ineffective. Stimulant use in children has been associated with growth suppression. Stimulants may unmask tics in individuals with coexisting Tourette's syndrome.

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypertension, tachycardia, palpitation

Central nervous system: Restlessness, headache, exacerbation of motor and phonic tics and Tourette's syndrome, dizziness, psychosis, dysphoria, overstimulation, euphoria, insomnia

Dermatologic: Rash, urticaria

Endocrine & metabolic: Change in libido

Gastrointestinal: Diarrhea, nausea, vomiting, stomach cramps, constipation, anorexia, weight loss, xerostomia, unpleasant taste

Genitourinary: Impotence

Neuromuscular & skeletal: Tremor

Miscellaneous: Suppression of growth in children, tolerance and withdrawal with prolonged use

Overdosage/Toxicology

Symptoms of overdose include seizures, hyperactivity, coma, hypertension

There is no specific antidote for amphetamine intoxication and the bulk of the treatment is supportive. Hyperactivity and agitation usually respond to reduced sensory input, however, with extreme agitation haloperidol (2-5 mg I.M. for adults) may be required. Hyperthermia is best treated with external cooling measures, or when severe or unresponsive, muscle paralysis with pancuronium may be needed. Hypertension is usually transient and generally does not require treatment unless severe. For diastolic blood pressures >110 mm Hg, a nitroprusside infusion should be initiated. Seizures usually respond to diazepam IVP and/or phenytoin maintenance regimens.

Drug Interactions

Substrate of CYP2D6 (major)

Acidifiers: Very large doses of potassium acid phosphate or ammonium chloride may increase the renal elimination of amphetamines due to urinary acidification

Alkalinizers: Large doses of sodium bicarbonate or other alkalinizers may increase renal tubular reabsorption (decreased elimination) and diminish the effect of amphetamine; includes potassium or sodium citrate and acetate

Antipsychotics: Efficacy of amphetamines may be decreased by antipsychotics; in addition, amphetamines may induce an increase in psychotic symptoms in some patients

CYP2D6 inhibitors: May increase the levels/effects of methamphetamine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Furazolidone: Amphetamines may induce hypertensive episodes in patients receiving furazolidone

Guanethidine: Amphetamines inhibit the antihypertensive response to guanethidine; probably also may occur with guanadrel

MAO inhibitors: Severe hypertensive episodes have occurred with amphetamine when used in patients receiving MAO inhibitors; concurrent use or use within 14 days is contraindicated

Norepinephrine: Amphetamines enhance the pressor response to norepinephrine

Sibutramine: Concurrent use of sibutramine and amphetamines may cause severe hypertension and tachycardia; use is contraindicated (benzphetamine)

SSRIs: Amphetamines may increase the potential for serotonin syndrome when used concurrently with selective serotonin reuptake inhibitors (including fluoxetine, fluvoxamine, paroxetine, and sertraline)

Tricyclic antidepressants: Concurrent of amphetamines with TCAs may result in hypertension and CNS stimulation; avoid this combination

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may cause CNS depression).

Food: Amphetamine serum levels may be altered if taken with acidic food, juices, or vitamin C. Avoid caffeine.

Herb/Nutraceutical: Avoid ephedra (may cause hypertension or arrhythmias).

Mechanism of Action

A sympathomimetic amine related to ephedrine and amphetamine with CNS stimulant activity; peripheral actions include elevation of systolic and diastolic blood pressure and weak bronchodilator and respiratory stimulant action

Pharmacodynamics/Kinetics

Absorption: Rapid from GI tract

Metabolism: Hepatic

Half-Life elimination: 4-5 hours

Excretion: Urine primarily (dependent on urine pH)

Dosage

Oral:

Children >6 years and Adults: ADHD: 2.5-5 mg 1-2 times/day; may increase by 5 mg increments at weekly intervals until optimum response is achieved, usually 20-25 mg/day

Children >12 years and Adults: Exogenous obesity: 5 mg 30 minutes before each meal; treatment duration should not exceed a few weeks

Monitoring Parameters

Heart rate, respiratory rate, blood pressure, and CNS activity

Dietary Considerations

Should be taken 30 minutes before meals.

Patient Education

Take exactly as directed; do not increase dose or frequency without consulting prescriber. Drug may cause physical and/or psychological dependence. Take early in day to avoid sleep disturbance, 30 minutes before meals. Avoid caffeine or OTC medications that act as stimulants. You may experience restlessness, false sense of euphoria, or impaired judgment (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); nausea or vomiting (small, frequent meals, frequent mouth care may help); constipation (increased exercise, fluids, fruit, or fiber may help); diarrhea (buttermilk, boiled milk, or yogurt may help); or altered libido (reversible). Patients with diabetes need to monitor serum glucose closely (may alter antidiabetic medication requirements). Report chest pain, palpitations, or irregular heartbeat; extreme fatigue or depression; CNS changes (aggressiveness, restlessness, euphoria, sleep disturbances); severe unremitting abdominal distress or cramping; blackened stool; changes in sexual activity; or blurred vision. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Nursing Implications

Dose should not be given in evening or at bedtime

Additional Information

Illicit methamphetamine may contain lead; alkalinizing urine can result in longer methamphetamine half-life and elevated blood level; ephedrine is a precursor in the illicit manufacture of methamphetamine; ephedrine is extracted by dissolving ephedrine tablets in water or alcohol (50,000 tablets can result in 1 kg of ephedrine); conversion to methamphetamine occurs at a rate of 50% to 70% of the weight of ephedrine. 3,4-methylene dioxymethamphetamine (slang: XTC, Ecstasy, Adam) affects the serotonergic, dopaminergic, and noradrenergic pathways. As such, it can cause the serotonin syndrome associated with malignant hyperthermia and rhabdomyolysis.

Cardiovascular Considerations

Amphetamines should be avoided in patients with known or suspected cardiovascular disease. They may precipitate marked increases in blood pressure, tachycardia, and tachyarrhythmias. These drugs are often used recreationally and inappropriately, particularly for appetite suppressant effects. Recreational use of amphetamines should be considered in otherwise healthy patients with new onset hypertension, tachycardia, or tachyarrhythmias.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Up to 10% of patients taking dextroamphetamines may present with hypertension. The use of local anesthetic without vasoconstrictor is recommended in these patients.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

Use vasoconstrictor with caution in patients taking methamphetamine. Amphetamines enhance the sympathomimetic response of epinephrine and norepinephrine leading to potential hypertension and cardiotoxicity.

Dosage Forms

Tablet, as hydrochloride: 5 mg

References

Catanzarite VA and Stein DA, "'Crystal' and Pregnancy: Methamphetamine-Associated Maternal Death," West J Med , 1995, 162(5):454-7.

Gilbert RB, Peng PI,and Wong D, "A Labetalol Metabolite With Analytical Characteristics Resembling Amphetamines," J Anal Toxicol , 1995, 19(2):84-6.

Gospe SM Jr, "Transient Cortical Blindness in an Infant Exposed to Methamphetamine," Ann Emerg Med , 1995, 26(3):380-2.

McKinney PF, Tomaszewski C, Phillips S, et al, "Methamphetamine Toxicity Prevented by Activated Charcoal in a Mouse Model," Ann Emerg Med , 1994, 24(2):220-2.

Mendelson J, Jones RT, Upton R, et al, "Methamphetamine and Ethanol Interactions in Humans," Clin Pharmacol Ther , 1995, 57(5):559-68.

Mueller PD and Korey WS, "Death by Ecstasy - The Serotonin Syndrome?" Clin Toxicol , 1995, 33(5):550.

Nestor TA, Tamamoto WI, Kam TH, et al, "Acute Pulmonary Oedema Caused by Crystalline Methamphetamine," Lancet , 1989, 2(8674):1277-8.

Richards CF, Clark RF, Holbrook T, et al, "The Effect of Cocaine and Amphetamines on Vital Signs in Trauma Patients," J Emerg Med , 1995, 13(1):59-63.

Rothrock JF, Rubenstein R, and Lyden PD, "Ischemic Stroke Associated With Methamphetamine Inhalation," Neurology , 1988, 38(4):589-92.

Segar DL, "Substances of Abuse: Topics," Emerg Med , 1985, 7:18-30.

Sperling LS and Horowitz JL, "Methamphetamine-Induced Choreoathetosis and Rhabdomyolysis," Ann Intern Med , 1994, 121(12):986.

International Brand Names

Desoxyn® (CA)

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