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Adderall (Dextroamphetamine Saccharate / Amphetamine Aspartate Monohydrate / Dextroamphetamine Sulfate / Amphetamine Sulfate) - Warnings and Precautions

 
 



AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED. 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.

MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS.

 

WARNINGS

Psychosis

Clinical experience suggests that in psychotic patients, administration of amphetamine may exacerbate symptoms of behavior disturbance and thought disorder.

Long-Term Suppression of Growth

Data are inadequate to determine whether chronic use of stimulants in children, including amphetamine, may be causally associated with suppression of growth. Therefore, growth should be monitored during treatment, and patients who are not growing or gaining weight as expected should have their treatment interrupted.

Sudden Death and Pre-existing Structural Cardiac Abnormalities

Sudden death has been reported in association with amphetamine treatment at usual doses in children with structural cardiac abnormalities. ADDERALL® generally should not be used in children or adults with structural cardiac abnormalities.

PRECAUTIONS

General

The least amount of amphetamine feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Hypertension

Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension (see CONTRAINDICATIONS). Blood pressure and pulse should be monitored at appropriate intervals in patients taking ADDERALL®, especially patients with hypertension. Sustained increases in blood pressure should be treated with dose reduction and/or appropriate medication.

Tics

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette's syndrome. Therefore, clinical evaluation for tics and Tourette's syndrome in children and their families should precede use of stimulant medications.

Effects on Weight

Amphetamines have been associated with decreased appetite. Absolute weight increases in treated children over time, but the increases are smaller than expected based on CDC normative values. These reductions in expected weight attenuate over time and are greatest in the heaviest children.

Information for Patients

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicles; the patient should therefore be cautioned accordingly.

Drug Interactions

Acidifying agents -Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines.

Urinary acidifying agents -(ammonium chloride, sodium acid phosphate, etc.) Increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic blocker - Adrenergic blockers are inhibited by amphetamines.

Alkalinizing agents -Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Co-administration of ADDERALL® and gastrointestinal alkalizing agents, such as antacids, should be avoided. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the actions of amphetamines.

Antidepressants, tricyclic - Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.

MAO inhibitors -MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines -Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives -Amphetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine -Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.

Ethosuximide -Amphetamines may delay intestinal absorption of ethosuximide.

Haloperidol -Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines.

Lithium carbonate -The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate.

Meperidine - Amphetamines potentiate the analgesic effect of meperidine.

Methenamine therapy -Urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy.

Norepinephrine - Amphetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital - Amphetamines may delay intestinal absorption of phenobarbital; co-administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin -Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.

Propoxyphene -In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Veratrum alkaloids -Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test Interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

Carcinogenesis/Mutagenesis and Impairment of Fertility

No evidence of carcinogenicity was found in studies in which d,l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose of 30 mg/day [child] on a mg/m2 body surface area basis.

Amphetamine, in the enantiomer ratio present in ADDERALL®(immediate-release)(d- to l- ratio of 3:1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro. d,l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.

Amphetamine, in the enantiomer ratio present in ADDERALL® (immediate-release)(d- to l- ratio of 3:1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day (approximately 5 times the maximum recommended human dose of 30 mg/day on a mg/m2 body surface area basis).

Pregnancy

Teratogenic Effects

Pregnancy Category C. Amphetamine, in the enantiomer ratio present in ADDERALL®(d- to l- ratio of 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 1.5 and 8 times, respectively, the maximum recommended human dose of 30 mg/day [child] on a mg/m2 body surface area basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 6 times that of a human dose of 30 mg/day [child] on a mg/m2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity.

A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d,l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function.

There are no adequate and well-controlled studies in pregnant women. There has been one report of severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Usage in Nursing Mothers

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use

Long-term effects of amphetamines in children have not been well established. Amphetamines are not recommended for use in children under 3 years of age with Attention Deficit Hyperactivity Disorder described under INDICATIONS AND USAGE.

Geriatric Use

ADDERALL® has not been studied in the geriatric population.

Page last updated: 2006-05-11

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