Amphetamine Interactions

Drug Interactions MAO inhibitors - MAOI antidepressants, as well as a metabolic 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. Serotonergic drugs - The concomitant use of amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the concomitant serotonergic drug(s) ( see WARNINGS and PRECAUTIONS ). CYP2D6 inhibitors - The concomitant use of amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the CYP2D6 inhibitor ( see WARNINGS and OVERDOSAGE ). Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. 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 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 blockers - Adrenergic blockers are inhibited by amphetamines. Alkalinizing agents - Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. 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 action 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. Antihistamines - Amphetamines may counteract the sedative effect of antihistamines. Antihypertensives - Amphetamines may antagonize the hypotensive effects of antihypertensives. Chlorpromazine - Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning. Ethosuximide - Amphetamines may delay intestinal absorption of ethosuximide. Haloperidol - Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. Lithium carbonate - The antiobesity 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 Interactions MAO Inhibitors Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS concomitantly or within 14 days after discontinuing MAOI [see CONTRAINDICATIONS and WARNINGS ]. Serotonergic Drugs The concomitant use of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS initiation or dosage increase. If serotonin syndrome occurs, discontinue DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. CYP2D6 Inhibitors The concomitant use of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and CYP2D6 inhibitors may increase the exposure of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS initiation and after a dosage increase. If serotonin syndrome occurs, discontinue DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents. Adrenergic Blockers Adrenergic blockers are inhibited by amphetamines. Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts). Adrenergic Blockers Adrenergic Blockers are inhibited by Amphetamines. Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents. Tricyclic Antidepressants May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response. 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; coadministration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Proton Pump Inhibitors Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole. Veratrum Alkaloids Amphetamines inhibit the hypotensive effect of veratrum alkaloids Adrenergic Blockers Adrenergic blockers are inhibited by amphetamines. Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents (e.g., sodium bicarbonate) and urinary alkalinizing agents (e.g. acetazolamide, some thiazides). Tricyclic Antidepressants May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response. Examples of tricyclic antidepressants include desipramine, protriptyline. CYP2D6 Inhibitors The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Examples of CYP2D6 inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Serotonergic Drugs The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort. MAO Inhibitors Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets concomitantly or within 14 days after discontinuing MAOI [see CONTRAINDICATIONS and WARNINGS ]. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. 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; coadministration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Proton Pump Inhibitors Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole. 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, 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/m 2 body surface area basis. Amphetamine, in the enantiomer ratio present in dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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 dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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/m 2 body surface area basis). Pregnancey Teratogenic Effects Pregnancy Category C Amphetamine, in the enantiomer ratio present in dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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/m 2 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/m 2 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 I NDICATIONS AND USAGE . Geriatric Use Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets have not been studied in the geriatric population.

7 DRUG INTERACTIONS Alkalinizing agents (GI antacids and urinary): These agents increase blood levels of amphetamine. ( 2.7 , 7.1 ) Acidifying agents (GI and urinary): These agents reduce blood levels of amphetamine. ( 7.1 ) 7.1 Clinically Important Interactions with Amphetamines Table 4: Drugs Having Clinically Important Interactions with Amphetamines Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Intervention Do not administer dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules concomitantly or within 14 days after discontinuing MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.8) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules and the CYP2D6 inhibitor [see Warnings and Precautions (5.8) and Overdosage (10) ]. Alkalinizing Agents Clinical Impact Increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate extended-release capsules and gastrointestinal or urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. Proton Pump Inhibitors Clinical Impact Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone. Intervention Monitor patients for changes in clinical effect and adjust therapy based on clinical response. 7.2 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.

Drug Interactions Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts). Adrenergic Blockers Adrenergic blockers are inhibited by amphetamines. Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents (e.g., sodium bicarbonate) and urinary alkalinizing agents (e.g. acetazolamide, some thiazides). Tricyclic Antidepressants May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response. Examples of tricyclic antidepressants include desipramine, protriptyline. CYP2D6 Inhibitors The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the CYP2D6 inhibitor [see WARNINGS, OVERDOSAGE ]. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Serotonergic Drugs The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort. MAO Inhibitors Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets concomitantly or within 14 days after discontinuing MAOI [see CONTRAINDICATIONS and WARNINGS ]. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. 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; coadministration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Proton Pump Inhibitors Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole. Veratrum Alkaloids Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug Interactions MAO Inhibitors Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS concomitantly or within 14 days after discontinuing MAOI [see CONTRAINDICATIONS and WARNINGS ]. Serotonergic Drugs The concomitant use of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS initiation or dosage increase. If serotonin syndrome occurs, discontinue DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. CYP2D6 Inhibitors The concomitant use of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and CYP2D6 inhibitors may increase the exposure of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS initiation and after a dosage increase. If serotonin syndrome occurs, discontinue DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents. Adrenergic Blockers Adrenergic blockers are inhibited by amphetamines. Acidifying Agents Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts). Adrenergic Blockers Adrenergic Blockers are inhibited by Amphetamines. Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents. Tricyclic Antidepressants May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response. 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; coadministration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Proton Pump Inhibitors Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole. Veratrum Alkaloids Amphetamines inhibit the hypotensive effect of veratrum alkaloids Adrenergic Blockers Adrenergic blockers are inhibited by amphetamines. Alkalinizing Agents Increase blood levels and potentiate the action of amphetamine. Co-administration of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents (e.g., sodium bicarbonate) and urinary alkalinizing agents (e.g. acetazolamide, some thiazides). Tricyclic Antidepressants May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response. Examples of tricyclic antidepressants include desipramine, protriptyline. CYP2D6 Inhibitors The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Examples of CYP2D6 inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Serotonergic Drugs The concomitant use of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort. MAO Inhibitors Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets concomitantly or within 14 days after discontinuing MAOI [see CONTRAINDICATIONS and WARNINGS ]. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue. 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; coadministration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Proton Pump Inhibitors Time to maximum concentration (T max ) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole. 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, 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/m 2 body surface area basis. Amphetamine, in the enantiomer ratio present in dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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 dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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/m 2 body surface area basis). Pregnancey Teratogenic Effects Pregnancy Category C Amphetamine, in the enantiomer ratio present in dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (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/m 2 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/m 2 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 I NDICATIONS AND USAGE . Geriatric Use Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets have not been studied in the geriatric population.