Phentermine Hydrochloride - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology.
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Phentermine Hydrochloride - Scientific Information

Manufacture: Epic Pharma LLC
Country: United States
Condition: Obesity, Weight Loss
Class: Anorexiants, CNS stimulants
Form: Capsules
Ingredients: phentermine hydrochloride, lactose monohydrate, magnesium stearate, talc, d&c red no . 3 3, fd&c blue no . 1, titanium dioxide, gelatin, shellac, ferro so ferric oxide, butyl alcohol, propylene glycol, alcohol, methyl alcohol, d&c yellow no . 10, fd&c blue no . 2, fd&c red no . 4 0

Description

Phentermine hydrochloride USP is a sympathomimetic amine anorectic. Its chemical name is α,α,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:



C10H15N•HCl M.W. 185.7

Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder which is soluble in water and lower alcohols, slightly soluble in chloroform and insoluble in ether.

Phentermine hydrochloride, an anorectic agent for oral administration, is available as a capsule containing 37.5 mg of phentermine hydrochloride (equivalent to 30 mg of phentermine base).

In addition, each capsule contains the following inactive ingredients: lactose monohydrate, magnesium stearate and talc. The capsule shell is composed of D&C Red No. 33, FD&C Blue No.1, titanium dioxide and gelatin. The imprinting ink contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No.1 Aluminum Lake, FD&C Blue No.2 Aluminum Lake and FD&C Red No. 40 Aluminum Lake.

Clinical Pharmacology

Mechanism of Action

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-amphetamine). Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics.” It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.

Pharmacodynamics

Typical actions of amphetamines 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.

Pharmacokinetics

Following the administration of phentermine, phentermine reaches peak concentrations (Cmax) after 3 to 4.4 hours.

Specific Populations

Renal Impairment

Phentermine was not studied in patients with renal impairment. The literature reported cumulative urinary excretion of phentermine under uncontrolled urinary pH conditions is 62% to 85%. Exposure increases can be expected in patients with renal impairment. Use caution when administering phentermine to patients with renal impairment.

Drug Interactions

In a single-dose study comparing the exposures after oral administration of a combination capsule of 15 mg phentermine and 92 mg topiramate to the exposures after oral administration of a 15 mg phentermine capsule or a 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of phentermine. However in the presence of topiramate, phentermine Cmax and AUC increase 13% and 42 % respectively.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies have not been performed with phentermine to determine the potential for carcinogenesis, mutagenesis or impairment of fertility.

Clinical Studies

In relatively short-term clinical trials, adult obese subjects instructed in dietary management and treated with “anorectic” drugs lost more weight on the average than those treated with placebo and diet.

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 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 drugs 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 over several 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 clinically limited.