BONTRIL

The structural formula is as follows:

Phendimetrazine tartrate is a white, odorless powder with a bitter taste bontril. It is soluble in water, methanol and ethanol bontril.

Bontril Slow-Release capsules contain FD&C Yellow No bontril. 6 as a color additive bontril.

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

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

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 bontril.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week bontril. 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 bontril. The possible origin of the increased weight loss due to the various drug effects is not established bontril. 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 bontril. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss bontril.

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 clinically limited bontril.

The active drug 105 mg of phendimetrazine tartrate in each capsule of this special slow-release dosage form approximates the action of three 35 mg non-time release doses taken at 4 hours intervals bontril.

The major route of elimination is via the kidneys where most of the drug and metabolites are excreted bontril. Some of the drug is metabolized to phenmetrazine and also phendimetrazine-N-oxide bontril.

The average half-life of elimination when studied under controlled conditions is about 1.9 hours for the non-time and 9.8 hours for the slow-release dosage form bontril. The absorption half-life of the drug from conventional non-time 35 mg phendimetrazine tartrate tablets is approximately the same bontril. These data indicate that the slow-release product has a similar onset of action to the conventional non-time-release product and, in addition, has a prolonged therapeutic effect bontril.

INDICATIONS
Phendimetrazine tartrate is indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction bontril. The limited usefulness of agents of this class (see ACTIONS ) should be measured against possible risk factors inherent in their use such as those described below bontril.

CONTRAINDICATIONS
Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate and severe hypertension, hyperthyroidism, known hypersensitivity, or idiosyncrasy to the sympathomimetic amines, glaucoma bontril. Agitated states bontril. Patients with a history of drug abuse bontril. Use in patients taking other CNS stimulants including monoamine oxidase inhibitors bontril.

WARNINGS
Tolerance to the anorectic effect usually develops within a few weeks bontril. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued bontril.

Use of phendimetrazine tartrate within 14 days following the administration of monoamine oxidase inhibitors may result in a hypertensive crisis bontril.

Abrupt cessation of administration following prolonged high dosage results in extreme fatigue and depression bontril. Because of the effect on the central nervous system phendimetrazine tartrate may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; the patient should therefore be cautioned accordingly bontril.

PRECAUTIONS
Caution is to be exercised in prescribing phendimetrazine tartrate for patients with even mild hypertension bontril.

Insulin requirements in diabetes mellitus may be altered in association with the use of phendimetrazine tartrate and the concomitant dietary regimen bontril.

Phendimetrazine tartrate may decrease the hypotensive effect of guanethidine bontril.

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

Usage in Pregnancy: Safe use in pregnancy has not been established bontril. Until more information is available, phendimetrazine tartrate should not be taken by women who are or may become pregnant unless, in the opinion of the physician, the potential benefits outweigh the possible hazards bontril.

Usage in Children: Phendimetrazine tartrate is not recommended for use in children under 12 years of age bontril.

ADVERSE REACTIONS
Cardiovascular: Palpitation, tachycardia, elevation of blood pressure bontril.

Central Nervous System: Overstimulation, restlessness, dizziness, insomnia, tremor, headache; rarely psychotic episodes at recommended doses, agitation, flushing, sweating, blurring of vision bontril.

Gastrointestinal: Dryness of the mouth, diarrhea, constipation, nausea, stomach pain bontril.

Genitourinary: Changes in libido, urinary frequency, dysuria bontril.

DRUG ABUSE AND DEPENDENCE
Controlled Substance: Phendimetrazine tartrate is a Schedule III controlled substance bontril.

Dependence: Phendimetrazine Tartrate is related chemically and pharmacologically to the amphetamines bontril. Amphetamines and related stimulant drugs have been extensively abused, and the possibility of abuse of phendimetrazine should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program bontril. Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction bontril. There are reports of patients who have increased the dosage to many times that recommended bontril. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG bontril. Manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes bontril. The most severe manifestation of chronic intoxications is psychosis, often clinically indistinguishable from schizophrenia bontril.

OVERDOSAGE
Manifestations of acute overdosage may include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states bontril.

Fatigue and depression usually follow the central stimulation bontril.

Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse bontril. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps bontril. Poisoning may result in convulsions, coma, and death bontril.

Management of acute intoxication is largely symptomatic and includes lavage and sedation with a barbiturate bontril. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard bontril.

Acidification of the urine increases phendimetrazine tartrate excretion bontril.

Intravenous phentolamine (Regitine) has been suggested for possible acute, severe hypertension, if this complicates overdosage bontril.

DOSAGE AND ADMINISTRATION
One Slow-Release Capsule (105 mg) in the morning, taken 30-60 minutes before the morning meal bontril.