Phendimetrazine

Usual Adult Dose for Obesity:

Extended-release:
-105 mg orally once a day, 30 to 60 minutes before morning meal

Immediate-release:
-35 mg orally 2 or 3 times a day, one hour before meals
-Maximum dose: 70 mg orally 3 times a day, one hour before meals

Comments:
-For use as monotherapy only.
-Extended-release: The active drug in each extended release capsule approximates the action of three 35 mg immediate-release doses taken at 4 hour intervals.
-Immediate-release: Dosage should be individualized to obtain an adequate response with the lowest effective dose; 17.5 mg per dose may be adequate in some cases.

Use: Management of exogenous obesity as a short-term adjunct in a regimen of weight reduction based on caloric restriction in patients with
-an initial BMI of 30 kg/m2 or greater OR
-an initial BMI of 27 kg/m2 or greater in the presence of other risk factors (e.g., hypertension, diabetes, hyperlipidemia) who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone.

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.

General

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

Insulin or oral hypoglycemic medication 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

Studies with Phendimetrazine tartrate sustained release have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy

Phendimetrazine tartrate is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy. Phendimetrazine tartrate, a phenylalkylamine sympathomimetic amine has pharmacological activity similar to amphetamines (see CLINICAL PHARMACOLOGY). Animal reproduction studies have not been conducted in Phendimetrazine tartrate. 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 a fetus.

Nursing Mothers

It is not known if Phendimetrazine tartrate is excreted in human milk. Phendimetrazine tartrate, a phenylalkylamine sympathomimetic amine, has pharmacological activity similar to the amphetamines (see CLINICAL PHARMACOLOGY), and other amphetamines are present in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Drug Interactions

Monoamine Oxidase Inhibitors

Use of Phendimetrazine tartrate is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis.

Alcohol

Concomitant use of alcohol with Phendimetrazine tartrate may result in an adverse drug reaction.

Insulin and Oral Hypoglycemic Medications

Requirements may be altered

Adrenergic Neuron Blocking Drugs

Phendimetrazine tartrate may decrease the hypotensive effect of adrenergic neuron blocking drugs.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Because pediatric obesity is a chronic condition requiring long-term treatment, the use of Phendimetrazine tartrate ER approved for short-term therapy, is not recommended in patients less that 17 years of age.

Renal Impairment

Phendimetrazine tartrate extended-release capsules were not studied in patients with renal impairment. As Phendimetrazine tartrate is excreted in urine, exposure increases can be expected in patients with renal impairment. Use caution when administering Phendimetrazine tartrate to patients with renal impairment.

Geriatric Use

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The major route of elimination is via the kidney where most of the drug and metabolites are excreted. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 24 Hour, Oral, as tartrate:

Generic: 105 mg

Tablet, Oral, as tartrate:

Bontril PDM: 35 mg [DSC] [scored; contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

Generic: 35 mg

Hypersensitivity or idiosyncrasy to phendimetrazine, other sympathomimetic amines, or any component of the formulation; glaucoma; highly nervous or agitated patients; history of drug abuse; hyperthyroidism; coadministration with other anorectic agents or CNS stimulants; during or within 14 days following monoamine oxidase inhibitors therapy.

Additional contraindications:

Extended-release: History of cardiovascular disease (eg, arrhythmias, heart failure, coronary artery disease, uncontrolled hypertension, pulmonary hypertension, stroke); pregnancy; breast-feeding

Immediate-release: Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate and severe hypertension

Refer to adult dosing.

Obesity (short-term): Oral: Adolescents ≥17 years: Extended-release: Refer to adult dosing.

Animal reproduction studies have not been conducted. Use is contraindicated by some manufacturers in pregnant women (lack of potential benefit and possible fetal harm). An increased risk of adverse maternal and fetal outcomes is associated with obesity; however, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015).

Phendimetrazine is a sympathomimetic amine, which is similar to an amphetamine. It is also known as an "anorectic" or "anorexigenic" drug. Phendimetrazine stimulates the central nervous system (nerves and brain), which increases your heart rate and blood pressure and decreases your appetite.

Phendimetrazine is used as a short-term supplement to diet and exercise in the treatment of obesity.

Phendimetrazine may also be used for purposes not listed in this medication guide.

Take phendimetrazine exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. This medicine should be taken only for a short time, such as a few weeks.

Phendimetrazine is usually taken once daily. Follow your doctor's instructions.

Take phendimetrazine on an empty stomach, 30 to 60 minutes before your morning meal. Do not crush, chew, break, or open the extended-release capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. You should lose at least 4 pounds during the first 4 weeks of taking phendimetrazine and eating a low calorie diet. Tell your doctor if you do not lose at least 4 pounds after taking the medication for 4 weeks.

Do not stop using phendimetrazine suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using this medicine.

Never take more of this medication than is prescribed for you. Too much phendimetrazine could be very dangerous to your health. Talk with your doctor if you have increased hunger or if you otherwise think the medication is not working properly. Taking more of this medication will not make it more effective and can cause serious, life-threatening side effects.

Store phendimetrazine at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.