Dextroamphetamine Sulfate

DEXTROAMPHETAMINE SULFATE- dextroamphetamine sulfate capsule, extended release
Actavis Pharma, Inc.

Rx only

DESCRIPTION

Dextroamphetamine Sulfate, USP is the dextro isomer of the compound d,l -amphetamine sulfate, a sympathomimetic amine of the amphetamine group. Chemically, dextroamphetamine is d -alpha-methylphenethylamine, and is present in all forms of dextroamphetamine sulfate extended-release as the neutral sulfate.

Structural formula:

Each extended-release capsule is so prepared that an initial dose is released promptly and the remaining medication is released gradually over a prolonged period.

Each 5 mg capsule, with a light brown opaque cap and body, contains 5 mg of dextroamphetamine sulfate, USP. The 5 mg capsule is printed with and 0303 on both cap and body in black ink.

Each 10 mg capsule, with a light brown opaque cap and light orange transparent body, contains 10 mg of dextroamphetamine sulfate, USP. The 10 mg capsule is printed with and 0304 on both cap and body in black ink.

Each 15 mg capsule, with a light brown opaque cap and light orange transparent body, contains 15 mg of dextroamphetamine sulfate, USP. The 15 mg capsule is printed with and 0305 on both cap and body in black ink.

Inactive ingredients: denatured alcohol, ammonium hydroxide, ethylcellulose, gelatin, hydroxypropyl cellulose, hypromellose, medium chain triglycerides, oleic acid, polyethylene glycol and sugar spheres (which contain sucrose and corn starch).

The capsule shells of the 5 mg, 10 mg and 15 mg contain black iron oxide, red iron oxide, silicon dioxide, sodium lauryl sulfate, talc, titanium dioxide and yellow iron oxide. In addition, the 10 mg and 15 mg capsule shell contains FD&C Red #40 and D&C Yellow #10.

The capsule shells are imprinted with black ink (TekPrint SW-9008, TekPrint SW-9010, or Opacode S-1-17823) which contains: ammonium hydroxide, black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.

CLINICAL PHARMACOLOGY

Amphetamines are noncatecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Dextroamphetamine sulfate extended-release capsules are formulated to release the active drug substance in vivo in a more gradual fashion than the standard formulation, as demonstrated by blood levels. The formulation has not been shown superior in effectiveness over the same dosage of the standard, noncontrolled-release formulations given in divided doses.

Pharmacokinetics

The pharmacokinetics of the tablet and extended-release capsule were compared in 12 healthy subjects. The extent of bioavailability of the extended-release capsule was similar compared to the immediate-release tablet. Following administration of three 5-mg tablets, average maximal dextroamphetamine plasma concentrations (C_max ) of 36.6 ng/mL were achieved at approximately 3 hours.

Following administration of one 15-mg extended-release capsule, maximal dextroamphetamine plasma concentrations were obtained approximately 8 hours after dosing. The average C_max was 23.5 ng/mL. The average plasma T _½ was similar for both the tablet and extended-release capsule and was approximately 12 hours. In 12 healthy subjects, the rate and extent of dextroamphetamine absorption were similar following administration of the extended-release capsule formulation in the fed (58 gm to 75 gm fat) and fasted state.

INDICATIONS AND USAGE

Dextroamphetamine sulfate extended-release capsules are indicated in:

Narcolepsy

Attention Deficit Disorder with Hyperactivity

As an integral part of a total treatment program that typically includes other measures (psychological, educational, social) for patients (ages 6 years to 16 years) with this syndrome. A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of the hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in 2 or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go”; excessive talking; blurting answers; can’t wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

Special Diagnostic Considerations

Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use of medical and special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presences of the required number of DSM-IV characteristics.

Need for Comprehensive Treatment Program

Dextroamphetamine sulfate extended-release is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Stimulants are not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.

CONTRAINDICATIONS

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.

Known hypersensitivity or idiosyncrasy to amphetamine.

In patients known to be hypersensitive to amphetamine, or other components of dextroamphetamine sulfate extended-release. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see ADVERSE REACTIONS].

Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see WARNINGS and Drug Interactions].