Didrex Description

DIDREX Tablets contain the anorectic agent benzphetamine hydrochloride. Benzphetamine hydrochloride is a white crystalline powder readily soluble in water and 95% ethanol. The chemical name for benzphetamine hydrochloride is d-N,α-Dimethyl-N-(phenylmethyl)-benzeneethanamine hydrochloride and its molecular weight is 275.82.

The structural formula (dextro form) is represented below:

Each DIDREX Tablet, for oral administration, contains 50 mg of benzphetamine hydrochloride.

Inactive Ingredients: Calcium Stearate, Corn Starch, Erythrosine Sodium. FD & C Yellow No. 6, Lactose, Povidone, Sorbitol.

Didrex - Clinical Pharmacology

Benzphetamine hydrochloride is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.

Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics". It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions, or metabolic effects, may be involved.

Adult obese subjects instructed in dietary management and treated with "anorectic" drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short-term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is the greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The possible origins of the increased weight loss due to the various drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered to be clinically limited.

Pharmacokinetic data in humans are not available.

Indications and Usage for Didrex

DIDREX Tablets are indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction in patients with an initial body mass index (BMI) of 30 kg/m2 or higher who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone. Below is a chart of Body Mass Index (BMI) based on various heights and weights. BMI is calculated by taking the patient's weight, in kilograms (kg), divided by the patient's height, in meters (m), squared. Metric conversions are as follows: pounds ÷2.2 = kg; inches × 0.0254 = meters. The limited usefulness of agents of this class (See CLINICAL PHARMACOLOGY) should be weighed against possible risks inherent in their use such as those described below.

DIDREX Tablets are indicated for use as monotherapy only.

Contraindications

DIDREX Tablets are contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to sympathomimetic amines, and glaucoma. Benzphetamine should not be given to patients who are in an agitated state or who have a history of drug abuse.

Hypertensive crises have resulted when sympathomimetic amines have been used concomitantly or within 14 days following use of monoamine oxidase inhibitors. DIDREX should not be used concomitantly with other CNS stimulants.

DIDREX may cause fetal harm when administered to a pregnant woman. Amphetamines have been shown to be teratogenic and embryotoxic in mammals at high multiples of the human dose. DIDREX is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Warnings

DIDREX Tablets should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter preparations and herbal products.

In a case-control epidemiological study, the use of anorectic agents was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than three months was associated with a 23-fold increase in the risk of developing pulmonary hypertension. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded. It should be noted that benzphetamine was not specifically studied in this case-control study.

The onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension. Under these circumstances, DIDREX Tablets should be immediately discontinued, and the patient should be evaluated for the possible presence of pulmonary hypertension.

Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. However, no cases of this valvulopathy have been reported when benzphetamine has been used alone.

The potential risk of possible serious adverse effects such as valvular heart disease and pulmonary hypertension should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect pre-existing valvular heart diseases or pulmonary hypertension prior to initiation of benzphetamine treatment. DIDREX Tablets are not recommended in patients with known heart murmur or valvular heart disease. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur. To limit unwarranted exposure and risks, treatment with DIDREX Tablets should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician and patient).

When tolerance to the anorectic effect develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.

DIDREX Tablets are not recommended for severely hypertensive patients or for patients with symptomatic cardiovascular disease including arrhythmias.

DIDREX Tablets are not recommended for patients who used any anorectic agents within the prior year.

Precautions

Adverse Reactions/Side Effects

The following have been associated with the use of benzphetamine hydrochloride:

Cardiovascular

Palpitation, tachycardia, elevation of blood pressure.

There have been isolated reports of cardiomyopathy and ischemic cardiac events associated with chronic amphetamine use.

Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine, both independently and especially when used in combination with other anorectic drugs, have been reported. However, no cases of this valvulopathy have been reported when DIDREX Tablets have been used alone.

CNS

Overstimulation, restlessness, dizziness, insomnia, tremor, sweating, headache; rarely, psychotic episodes at recommended doses; depression following withdrawal of the drug.

Gastrointestinal

Dryness of the mouth, unpleasant taste, nausea, diarrhea, other gastrointestinal disturbances.

Allergic

Urticaria and other allergic reactions involving the skin.

Endocrine

Changes in libido.

Drug Abuse and Dependence

Benzphetamine is a controlled substance under the Controlled Substance Act by the Drug Enforcement Administration and has been assigned to Schedule III.

Benzphetamine hydrochloride is related chemically and pharmacologically to the amphetamines. Amphetamines and related stimulant drugs have been extensively abused, and the possibility of abuse of DIDREX Tablets should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction. There are reports of patients who have increased the dosage to many times that 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 anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.

Overdosage

Didrex Dosage and Administration

Dosage should be individualized according to the response of the patient. The suggested dosage ranges from 25 to 50 mg one to three times daily. Treatment should begin with 25 to 50 mg once daily with subsequent increase in individual dose or frequency according to response. A single daily dose is preferably given in mid-morning or mid-afternoon, according to the patient's eating habits. In an occasional patient it may be desirable to avoid late afternoon administration. Use of benzphetamine hydrochloride is not recommended in individuals under 12 years of age.

How is Didrex supplied

DIDREX Tablets are supplied as follows:

50 mg (peach, round, imprinted with DIDREX 50, scored)

Bottles of 100 NDC 0009-0024-01

Bottles of 500 NDC 0009-0024-02

Rx only

Manufactured by:
Patheon Puerto Rico, Inc.
Manati, PR 00674

LAB-0028-5.0
August 2010

PRINCIPAL DISPLAY PANEL - 100 Tablet Label

NDC 0009-0024-01

100 Tablets
Rx only

Didrex®
benzphetamine
hydrochloride
tablets

CIII

50 mg

Pfizer
Distributed by
Pharmacia & Upjohn Co
Division of Pfizer Inc, NY, NY 10017