DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS   CII

(Three Medication Guides Attached)

Revised MARCH 2007

11001193

Rx only

A single entity amphetamine product combining the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d, l-amphetamine aspartate.

In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, compressible sugar, corn starch, magnesium stearate, microcrystalline cellulose and, saccharin sodium.

The 5, 7.5 and 10 mg also contain FD&C blue no.1 aluminum lake.

The 12.5, 15, 20 and 30 mg also contain FD&C yellow no. 6 aluminum lake.

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action.

There is neither specific evidence which clearly establishes the mechanism whereby amphetamine produces mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets contain d-amphetamine and 1-amphetamine salts in the ratio of 3:1. Following administration of a single dose 10 or 30 mg of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets to healthy volunteers under fasted conditions, peak plasma concentrations occurred approximately 3 hours post-dose for both d-amphetamine and 1-amphetamine. The mean elimination half-life (t_½) for d-amphetamine was shorter than the t_½ of the 1-isomer (9.77 to 11 hours vs. 11.5 to 13.8 hours). The PK parameters (C_max, AUC_0-inf) of d- and 1-amphetamine increased approximately three-fold from 10 mg to 30 mg indicating dose-proportional pharmacokinetics.

The effect of food on the bioavailability of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate has not been studied.

Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets are  indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).

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

Data are inadequate to determine whether chronic administration of amphetamine may be associated with growth inhibition; therefore, growth should be monitored during treatment.

Sudden death has been reported in association with amphetamine treatment at usual doses in children with structural cardiac abnormalities. Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets generally should not be used in children or adults with structural cardiac abnormalities.

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

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

Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension. Blood pressure and pulse should be monitored at appropriate intervals in patients taking dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets, especially patients with hypertension.

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.

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with amphetamine or dextroamphetamine and should counsel them in its appropriate use. A patient Medication Guide is available for Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets.

The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its spans. Patients should be given the opportunity to discuss the spans of the Medication Guide and to obtain answers to any questions they may have. The complete div of the Medication Guide is reprinted at the end of this document.

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

Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of amphetamine, have not been performed.

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 Disorder with Hyperactivity described under INDICATIONS AND USAGE.

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.

Drug treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics. When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, depression, tremor, headache, exacerbation of motor and phonic tics and Tourette's syndrome, seizures, stroke.

Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect.

Urticaria.

Impotence, changes in libido.

Dextroamphetamine Sulfate is a Schedule II controlled substance.

Amphetamines have been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred. There are reports of patients who have increased the dosage to many times than recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines.

Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.

In rats, the oral LD₅₀ of dextroamphetamine sulfate is 96.8 mg/kg.

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis.

Fatigue and depression usually follow the central stimulation.

Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse.

Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

Consult with a Certified Poison Control Center for up to date guidance and advice. Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved. Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

Regardless of indication, amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Not recommended for children under 3 years of age. In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

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

Usual dose 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets is available as:

5 mg: Blue, oval, biconvex tablet with two partial bisects on one side debossed with stylized b over 971 and four partial bisects on the other side debossed with 5.

Available in bottles of:

7.5 mg: Blue, round, flat-faced, beveled-edge tablet debossed with stylized b over 775 on one side and two partial bisects and a full score on the other side debossed with 7│½.

Available in bottles of:

10 mg: Blue, oval, flat-faced, beveled-edge tablet with two partial bisects on one side debossed with stylized b over 972 and two partial bisects and a full score on the other side debossed with 1│0.

Available in bottles of:

12.5 mg: Peach, oval, biconvex tablet debossed with stylized b over 776 separated by a full score on one side and four partial bisects on the other side debossed with 12│½.

Available in bottles of:

15 mg: Peach, round, flat-faced, beveled-edge tablet debossed with stylized b over 777 on one side and two partial bisects and a full score on the other side debossed with 1│5.

Available in bottles of:

20 mg: Peach, oval, flat-faced, beveled-edge tablet with two partial bisects on one side debossed with stylized b over 973 and two partial bisects and a full score on the other side debossed with 2│0.

Available in bottles of:

30 mg: Peach, oval, biconvex tablet with two partial bisects on one side debossed with stylized b over 974 and two partial bisects and a full score on the other side debossed with 3│0.

Available in bottles of:

Dispense with a child-resistant closure in a tight, light-resistant container.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

DEXTROAMPHETAMINE SACCHARATE, AMPHETAMINE ASPARTATE, DEXTROAMPHETAMINE SULFATE AND AMPHETAMINE SULFATE TABLETS

Rx only

Read the Medication Guide that comes with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about you or your child’s treatment with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets.

MANUFACTURED BY
BARR LABORATORIES, INC.
POMONA, NY 10970

Revised MARCH 2007 / BR-0971, 0775, 0972, 0776, 0777, 0973, 0974