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CIV

Diethylpropion hydrochloride, a sympathomimetic agent. Chemically, diethylpropion hydrochloride is 1-phenyl-2-diethylamino-1-propanone hydrochloride.

Structural formula: C₁₃H₁₈NO HCl

Molecular weight: 241.76

Each tablet contains diethylpropion hydrochloride 75 mg in a controlled-release formulation. Diethylpropion hydrochloride tablets also contain: carbomer, mannitol, povidone, tartaric acid and zinc stearate.

Diethylpropion hydrochloride is dispersed in a hydrophilic matrix. On exposure to water the diethylpropion hydrochloride is released at a relatively uniform rate as a result of slow hydration of the matrix. The result is controlled release of the anorexic agent.

Diethylpropion hydrochloride is a sympathomimetic amine with some pharmacologic activity similar to that of the prototype drugs of this class used in obesity, the amphetamines. Actions include some central nervous system stimulation and elevation of blood pressure. Tolerance has 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, for example.

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 averages some fraction of a pound a week. However, individual weight loss may vary substantially from patient to patient. The rate of weight loss is 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 relationship, 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 most studies cited are restricted to a few weeks duration. Thus, the total impact of drug-induced weight loss over that of diet alone is unknown.

Diethylpropion is rapidly absorbed from the GI tract after oral administration and is extensively metabolized through a complex pathway of biotransformation involving N-dealkylation and reduction. Many of these metabolites are biologically active and may participate in the therapeutic action of these drugs. Due to the varying lipid solubilities of these metabolites, their circulating levels are affected by urinary pH. Diethylpropion and/or its active metabolites are believed to cross the blood-brain barrier and the placenta (see Labor and Delivery).

Diethylpropion and its metabolites are excreted mainly by the kidney. It has been reported that between 75-106% of the dose is recovered in the urine within 48 hours after dosing. Using a phosphorescence assay that is specific for basic compounds containing a benzoyl group, the plasma half-life of the aminoketone metabolites is estimated to be between 4 to 6 hours.

The controlled-release characteristics of Diethlpropion have been demonstrated by studies in humans in which plasma levels of diethylpropion-related material were measured by phosphorescence analysis. Plasma levels obtained with the 75 mg Diethylpropion formulation administered once daily indicated a more gradual release than the standard formulation, however, it has not been shown superior in effectiveness to the same dosage of the standard, non-controlled-release formulation.

Diethylpropion hydrochloride tablets are indicated in the management of exogenous obesity as a short-term adjunct (a few weeks) in a regiment of weight reduction based on caloric restriction. The usefulness of agents of this class should be measured against possible risk factors inherent in their use such as those described (see CLINICAL PHARMACOLOGY).

Diethylpropion hydrochloride should not be used in patients with advanced arteriosclerosis, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma, severe hypertension, a history of drug abuse, or those in an agitated state (see PRECAUTIONS).

Diethylpropion hydrochloride should not be given during, or within fourteen days following, the administration of monoamine oxidase inhibitors; hypertensive crises may result.

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

The following adverse effects, listed by organ system, have been associated with the use of Diethylpropion hydrochloride.

The reported oral LD₅₀, for diethylpropion hydrochloride in mice is 620 mg/kg. In rats 250 mg/kg and in dogs 225 mg/kg.

Diethylpropion hydrochloride 75 mg (controlled release) tablets: One tablet daily, swallowed whole, in mid-morning.

Diethylpropion hydrochloride 75 mg tablets are oval, white, domed, imprinted “2690V” on one side and plain on the other.

Diethylpropion hydrochloride 75 mg tablets are supplied in bottles of 100 and 250.

Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure. Store at controlled room temperature, 15°- 30°C (59°- 86°F).

Federal law prohibits dispensing without prescription.

Manufactured by:
3M Pharmaceuticals
Northridge, CA 91324

Manufactured for:
Qualitest Products, Inc.

IN99
Rev 2/95
R1