VA Class:CN801

AHFS Class:

• Amphetamines 28:20.04

Generic Name(s):

• Methamphetamine Hydrochloride

Methamphetamine hydrochloride, the dextrorotatory isomer of phenylmethylamine, has pharmacologic actions that are qualitatively similar to those of amphetamine and ephedrine.

Methamphetamine has been used as an adjunct to caloric restriction in the short-term (i.e., a few weeks) treatment of exogenous obesity. However, short-term or intermittent therapy with methamphetamine is unlikely to maintain a long-term benefit, and prolonged administration of methamphetamine for the treatment of obesity is not indicated. Methamphetamine also is used as an adjunct to psychological, educational, social, and other remedial measures in the treatment of attention deficit hyperactivity disorder (ADHD). Methamphetamine also has been misused and abused for its CNS stimulatory effects.

Exogenous Obesity

Methamphetamine has been used as an adjunct to caloric restriction in the short-term (i.e., a few weeks) treatment of exogenous obesity. The anorexigenic effect of sympathomimetic compounds used in the treatment of obesity is temporary, seldom lasting more than a few weeks, and tolerance may occur. However, obesity usually is a chronic disease, and short-term or intermittent therapy with these drugs is unlikely to maintain a long-term benefit; therefore, short-term use of anorexigenic agents, including methamphetamine, is not recommended. Furthermore, prolonged administration of methamphetamine in the treatment of obesity is not indicated. (See Cautions: Precautions and Contraindications.) To help bring about and maintain loss of weight, the patient must be taught to curtail overeating and to consume a suitable diet. For further information on the treatment of exogenous obesity, see Uses: Exogenous Obesity, in the Amphetamines General Statement 28:20.04.

Attention Deficit Hyperactivity Disorder

Methamphetamine also is used as an adjunct to psychological, educational, social, and other remedial measures in the treatment of ADHD (hyperkinetic disorder, hyperkinetic syndrome of childhood, minimal brain dysfunction) in children older than 6 years of age.

Methamphetamine should not be used to combat fatigue or exhaustion or to replace sleep in normal persons.

ADHD usually is characterized by developmentally inappropriate symptoms (e.g., moderate to severe distractibility, short attention span, hyperactivity, emotional lability, impulsivity). The final diagnosis of this disorder should not be made if these symptoms are of only comparatively recent origin. Nonlocalizing (soft) neurologic signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of CNS dysfunction may or may not be warranted. Drug therapy is not indicated in all children with ADHD, and such therapy should be considered only after a complete evaluation including medical history has been performed. The decision to use amphetamines should depend on the age of the child and the physician's assessment of the severity and duration of symptoms and should not depend solely on one or more behavioral characteristics. When symptoms of ADHD are associated with acute stress reactions, use of amphetamines usually is not recommended. For a more detailed discussion on the management of ADHD, including the use of stimulants such as methamphetamine, see Uses: Attention Deficit Hyperactivity Disorder, in Methylphenidate 28:20.32.

Misuse and Abuse

Misuse and abuse of amphetamines, especially methamphetamine, for CNS stimulatory effects have experienced a resurgence. In large part, this resurgence has resulted from the relative ease with which methamphetamine can be synthesized clandestinely from readily available chemicals such as ephedrine, phenylpropanolamine (no longer commercially available in the US), or pseudoephedrine. (See Chronic Toxicity, in the Amphetamines General Statement 28:20.04.) Legal restrictions, including enactment of the US Comprehensive Methamphetamine Control Act of 1996 and later the Methamphetamine Anti-Proliferation Act of 2000 and the Combat Methamphetamine Epidemic Act of 2005, on the availability of these compounds have been enacted in an effort to reverse this resurgence in misuse and abuse.

Administration

Methamphetamine hydrochloride is administered orally. Because of the potential for insomnia, administration of methamphetamine in the late evening should be avoided.

Dosage

Dosage and potency of methamphetamine hydrochloride are expressed in terms of the hydrochloride. (See Chemistry and Stability: Chemistry.)

Dosage of methamphetamine hydrochloride should be adjusted according to individual response and tolerance; the smallest dose required to produce the desired response should always be used.

Exogenous Obesity

As an adjunct in the treatment of exogenous obesity, the usual adult dosage of methamphetamine hydrochloride is 2.5-5 mg 2 or 3 times daily, given one-half hour before meals. Treatment should not exceed a duration of a few weeks.

Attention Deficit Hyperactivity Disorder

As an adjunct in the treatment of attention deficit hyperactivity disorder (ADHD) in children 6 years of age and older, the usual initial dosage of methamphetamine hydrochloride is 5 mg once or twice daily. Daily dosage may be increased by 5 mg at weekly intervals until an optimum clinical response is achieved. The usual effective dosage is 20-25 mg daily. The total daily dose may be given as conventional tablets in 2 divided doses daily.

When possible, therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued treatment.

Methamphetamine shares the toxic potentials of amphetamines, and the usual cautions, precautions, and contraindications of amphetamine therapy should be observed. (See Cautions, in the Amphetamines General Statement 28:20.04.)

Cardiovascular Effects

Sudden death, stroke, myocardial infarction, hypertension or hypotension, tachycardia, palpitation, or cardiac arrhythmias may occur in patients receiving stimulants, including methamphetamine. (See Cardiovascular Precautions under Cautions: Precautions and Contraindications, in the Amphetamines General Statement 28:20.04.) Fatal cardiorespiratory arrest has been reported following abuse or misuse of methamphetamine.

Nervous System Effects

Adverse nervous system effects of methamphetamine may include nervousness, insomnia, irritability, talkativeness, dizziness, headache, blurred vision, mydriasis, dizziness, dysphoria, euphoria, tremor, restlessness and hyperexcitability. Rarely, psychotic episodes have occurred in patients receiving recommended dosages. The drug may also exacerbate motor and vocal tics and Tourette's disorder. Seizures, aggressive behavior, and hostility also have been reported with stimulants. (See Psychiatric Precautions under Cautions: Precautions and Contraindications, in the Amphetamines General Statement 28:20.04.)

GI Effects

GI disturbances of methamphetamine may include nausea, vomiting, abdominal cramps, diarrhea or constipation, dryness of the mouth, anorexia, and unpleasant taste.

Other Adverse Effects

Urticaria, impotence, and changes in libido may occur in patients receiving methamphetamine. Visual disturbances (difficulty with accommodation, blurred vision) have been reported with stimulants.

Precautions and Contraindications

The manufacturer's patient information (medication guide) should be provided to the patient or caregiver each time methamphetamine is dispensed, and the clinician should discuss and answer questions about its contents (e.g., benefits and risks of stimulant therapy, appropriate use) as needed. The patient or caregiver also should be instructed to read and understand the contents of the medication guide before initiating therapy and each time the prescription is refilled.

Patients should be warned that methamphetamine may impair their ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).

Methamphetamine should be administered with caution, if at all, to patients with hyperexcitability states or to those receiving drugs that may produce this effect. The drug also should be used with caution in geriatric, debilitated, mildly hypertensive, or asthenic patients or in those with psychopathic personalities or history of suicidal or homicidal tendencies.

Methamphetamine has a high potential for abuse. Misuse and/or abuse of methamphetamine have resulted in serious adverse cardiovascular effects and death, including fatal cardiorespiratory arrest. The possibility of psychic dependence or addiction should be kept in mind, particularly when methamphetamine is administered to alcoholic patients or to those known to have been addicted to other drugs. Administration of methamphetamine for prolonged periods of time in the treatment of obesity may lead to drug dependence and must be avoided. The possibility that methamphetamine may be obtained for nontherapeutic use and distributed to others should be considered, and the drug should be prescribed or dispensed sparingly. Abrupt withdrawal of methamphetamine following prolonged administration of high dosage may result in psychotic manifestations, lethargy, and depression, which may persist for some weeks.

Methamphetamine is contraindicated in patients with hyperthyroidism, advanced arteriosclerosis, glaucoma, moderate to severe hypertension, or symptomatic cardiovascular disease, and in those with a previous history of hypersensitivity or idiosyncrasy to sympathomimetic amines. The drug is also contraindicated in patients in agitated states or with a history of drug abuse and during or within 14 days of administration of monoamine oxidase inhibitors.

For additional information on the precautions and contraindications of methamphetamine and other amphetamines, see Cautions: Precautions and Contraindications, in the Amphetamines General Statement 28:20.04.

Pediatric Precautions

Methamphetamine is not recommended for use as an anorexigenic agent in children younger than 12 years of age.

Therapy with CNS stimulants may be associated with at least a temporary suppression of growth in children. (See Cautions: Pediatric Precautions, in the Amphetamines General Statement 28:20.04.)

Geriatric Precautions

Clinical studies of methamphetamine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. While other reported clinical experience has not revealed age-related differences in response, dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy observed in this population also should be considered.

Pregnancy and Lactation

Pregnancy

Methamphetamine has been shown to have teratogenic and embryocidal effects in mammals receiving doses exceeding the usual therapeutic human dosage. There are no adequate and controlled studies to date in pregnant women. Methamphetamine should not be used during pregnancy unless the potential benefits justify the possible risks to the fetus.

Lactation

Amphetamines are distributed into milk. Therefore, nursing should be avoided during therapy with amphetamines.

Antidepressants

Neurologic and circulatory reactions have been reported in patients who have received parenteral methamphetamine concomitantly with monoamine oxidase inhibitor drugs, and fatalities have occurred. Methamphetamine is therefore contraindicated during or within 14 days of administration of monoamine oxidase inhibitors.

Patients receiving concomitant therapy with tricyclic antidepressants and indirect-acting sympathomimetic amines (e.g., amphetamines) should be closely monitored, and dosage carefully adjusted.

General Anesthetics

Methamphetamine should not be used to prevent hypotension in patients who have undergone general anesthesia with drugs (cyclopropane, halothane) that sensitize the heart to the arrhythmic action of sympathomimetic amines.

Guanethidine

Methamphetamine may decrease the hypotensive effect of guanethidine (no longer commercially available in the US).

Phenothiazines

Phenothiazines reportedly antagonize the CNS stimulant effect of amphetamines.

Other Drugs

Insulin requirements in patients with diabetes mellitus may be decreased in association with the use of methamphetamine and the concomitant dietary regimen and weight loss; therefore, methamphetamine should be administered with caution in patients with diabetes mellitus.

Laboratory Test Interferences

Amphetamines may substantially increase plasma corticosteroid concentrations.

Pharmacology

The pharmacologic actions of methamphetamine are qualitatively similar to those of amphetamine and ephedrine and include CNS and respiratory stimulation, and sympathomimetic activity including pressor response, mydriasis, bronchodilation, and contraction of the urinary bladder sphincter. The drug depresses the motility of the GI tract. The CNS stimulating effect of methamphetamine is approximately equal to or greater than that of amphetamine but less than that of dextroamphetamine; the pressor effect of methamphetamine is less than that of amphetamine but greater than that of ephedrine. Small doses of methamphetamine have a pronounced effect on the CNS without substantial peripheral action, but in larger doses the drug produces a sustained rise in blood pressure resulting mainly from cardiac stimulation. Methamphetamine apparently produces an anorexigenic effect and loss of weight. As with other amphetamine derivatives, no primary effect on appetite has been demonstrated and it is probable that its anorexigenic effect is secondary to CNS stimulation.

Pharmacokinetics

Methamphetamine is readily absorbed from the GI tract and effects persist for 6-12 hours but may continue up to 24 hours after large doses.

Methamphetamine is metabolized in the liver by aromatic hydroxylation, N -dealkylation, and deamination; at least 7 metabolites have been identified in urine. The biologic half-life of methamphetamine reportedly is 4-5 hours. Methamphetamine is eliminated principally in urine. Urinary excretion of the drug is pH dependent, and excretion is enhanced in acidic urine. Following oral administration of methamphetamine hydrochloride, approximately 62% of the administered dose is excreted in urine within the first 24 hours, with metabolites and unchanged drug accounting for about two-thirds and one-third, respectively, of the recovered drug.

Chemistry and Stability

Chemistry

Methamphetamine hydrochloride is the dextrorotatory isomer of phenylisopropylmethylamine. The drug occurs as white crystals or as a white, crystalline powder and is freely soluble in water (1:2) and in alcohol (1:3).

USP temporarily stated that potency of methamphetamine hydrochloride tablets should be expressed both in terms of the salt and the base (“active moiety”). However, USP recently reverted to its previous standard that potency be expressed only in terms of methamphetamine hydrochloride. Dosage currently continues to be expressed in terms of the salt. Therefore, care should be taken to avoid confusion between potencies that during a transitional period may be labeled as the salt and/or base and dosage of methamphetamine hydrochloride.

Stability

Methamphetamine hydrochloride preparations should be stored in tight, light-resistant containers and at a temperature less than 30°C.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, and dosage and administration of amphetamines, see the Amphetamines General Statement 28:20.04.

Please see the general statement for a list of references.