Phendimetrazine Tartrate 105 mg Capsule, Extended Release, 1,000-count — NDC 72989-409-11 (Billing 72989-0409-11)

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. 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.

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.

ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: • Primary pulmonary hypertension (see WARNINGS ) • Valvular heart disease (see WARNINGS ) • Effect on the ability to engage in potentially hazardous tasks (see WARNINGS ) • Withdrawal effects following prolonged high dosage administration (see DRUG ABUSE AND DEPENDENCE ) The following adverse reactions to phendimetrazine have been identified: Cardiovascular Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevated blood pressure, ischemic events.

Central Nervous System Overstimulation, restlessness, insomnia, agitation, flushing, tremor, sweating, dizziness, headache, psychotic state, blurring of vision. Gastrointestinal Dryness of the mouth, nausea, stomach pain, diarrhea, constipation. Genitourinary Urinary frequency, dysuria, changes in libido.

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.

PRECAUTIONS 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 than 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.

DRUG ABUSE AND DEPENDENCE Controlled Substance Phendimetrazine tartrate extended-release capsules are defined by the Drug Enforcement Administration as a Schedule III controlled substance. Abuse Phendimetrazine tartrate is related chemically and pharmacologically to the amphetamines. 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.

Dependence Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction. There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG.

Manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxications is psychosis, often clinically indistinguishable from schizophrenia.

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