PHENDIMETRAZINE TARTRATE

Apotheca, Inc.

Phendimetrazine Tartrate 105mg ER Capsule CIII Rx Only

FULL PRESCRIBING INFORMATION: CONTENTS*

• PHENDIMETRAZINE TARTRATE DESCRIPTION
• CLINICAL PHARMACOLOGY
• PHENDIMETRAZINE TARTRATE INDICATIONS AND USAGE
• PHENDIMETRAZINE TARTRATE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Usage in Pregnancy
  • Drug Interactions
  • Pediatric Use
• PHENDIMETRAZINE TARTRATE ADVERSE REACTIONS
• DRUG ABUSE AND DEPENDENCE
• OVERDOSAGE
• PHENDIMETRAZINE TARTRATE DOSAGE AND ADMINISTRATION
• storage and dispensing
• HOW SUPPLIED
• PACKAGE LABEL AND PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

PHENDIMETRAZINE TARTRATE DESCRIPTION

Phendimetrazine tartrate, as the dextro isomer, has the chemical name of (2S,3S)-3,4-dimethyl-2-phenylmorpholine L-(+)-tartrate (1:1).

The structural formula is as follows:

Phendimetrazine tartrate is a white, odorless crystalline powder.

It is freely soluble in water; sparingly soluble in warm alcohol, insoluble in chloroform, acetone, ether and benzene. Each capsule, for oral administration, contains 105 mg Phendimetrazine Tartrate manufactured in a special base designed for prolonged release. Inactive ingredients: FD and C Blue No. 1, FD and C Red No. 40, gelatin, pharmaceutical glaze, povidone, silica gel, sodium lauryl sulfate, corn starch, sucrose, talc and trace amounts of red imprinting ink.

CLINICAL PHARMACOLOGY

Phendimetrazine tartrate is a phenylalkylamine sympathomimetic amine with pharmacological 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, 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 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 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 clinically limited.

The active drug, 105 mg of Phendimetrazine Tartrate in each capsule of this special extended-release dosage form approximates the action of three 35 mg immediate release doses taken at four hour intervals.

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

The average half-life of elimination when studied under controlled conditions is about 3.7 hours for both the extended-release and immediate release forms. The absorption half-life of the drug from the immediate release 35 mg phendimetrazine tablets is appreciably more rapid than the absorption rate of the drug from the extended-release formulation

PHENDIMETRAZINE TARTRATE INDICATIONS AND USAGE

Phendimetrazine tartrate extended-release capsules are 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 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

Phendimetrazine tartrate is indicated for use as monotherapy only.

PHENDIMETRAZINE TARTRATE CONTRAINDICATIONS

Known hypersensitivity or idiosyncratic reactions to sympathomimetics.

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate and severe hypertension, pulmonary hypertension, hyperthyroidism and glaucoma. Highly nervous or agitated patients. Patients with a history of drug abuse. Patients taking other CNS stimulants, including monoamine oxidase inhibitors. Use in combination with other anorectic agents is contraindicated.

WARNINGS

Phendimetrazine tartrate 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, including phendimetrazine tartrate, 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.

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, phendimetrazine tartrate 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 phendimetrazine tartrate 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 preexisting valvular heart diseases or pulmonary hypertension prior to initiation of phendimetrazine treatment. Phendimetrazine tartrate is 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 phendimetrazine tartrate 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).

Tolerance to the anorectic effect of phendimetrazine develops within a few weeks. When this occurs, its use should be discontinued; the maximum recommended dose should not be exceeded. Use of phendimetrazine tartrate within 14 days following the administration of monoamine oxidase inhibitors may result in a hypertensive crisis. Abrupt cessation of administration following prolonged high dosage results in extreme fatigue and depression. Because of the effect on the central nervous system, phendimetrazine 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.

Phendimetrazine tartrate is not recommended for patients who used any anorectic agents within the prior year.

PRECAUTIONS

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

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

Phendimetrazine may decrease the hypotensive effect of guanethidine.

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Animal reproduction studies have not been conducted with Phendimetrazine Tartrate sustained release. It is also not known whether Phendimetrazine Tartrate sustained release can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Phendimetrazine Tartrate sustained release should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Usage in Pregnancy

Drug Interactions

Pediatric Use

PHENDIMETRAZINE TARTRATE ADVERSE REACTIONS

Palpitation, tachycardia, elevated blood pressure.

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 case of this valvulopathy has been reported when phendimetrazine tartrate has been used alone.

DRUG ABUSE AND DEPENDENCE

Phendimetrazine tartrate extended-release capsules are defined by the Drug Enforcement Administration as a Schedule III controlled substance.

OVERDOSAGE

Acute overdosage with phendimetrazine tartrate may manifest itself by the following signs and symptoms: unusual restlessness, confusion, belligerence, hallucinations, and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Poisoning may result in convulsions, coma, and death.

The management of overdosage is largely symptomatic. It includes sedation with a barbiturate. If hypertension is marked, the use of a nitrate or rapid-acting alpha receptor-blocking agent should be considered. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations for its use.

PHENDIMETRAZINE TARTRATE DOSAGE AND ADMINISTRATION

Since the product is an extended-release dosage form, limit to one extended-release capsule (105 mg Phendimetrazine Tartrate) in the morning (30-60 minutes before morning meal).
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storage and dispensing

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Protect from moisture.

DISPENSE IN A TIGHT CONTAINER AS DEFINED IN THE USP.

HOW SUPPLIED

• 12634-910-91 Blister Pack UD 
• 12634-910-97 Bottle of 7
  
• 12634-910-84 Bottle of 14
• 12634-910-85 Bottle of 15
• 12634-910-78 Bottle of 28
• 12634-910-71 Bottle of 30
• 12634-910-60 Bottle of 60

PACKAGE LABEL AND PRINCIPAL DISPLAY PANEL