ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. Cardiovascular: Primary pulmonary hypertension and/or regurgitant cardiac valvular disease (see WARNINGS), palpitation, tachycardia, elevation of blood pressure.Central Nervous System: Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache; rarely psychotic episodes at recommended doses.Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances.Allergic: Urticaria.Endocrine: Impotence, changes in libido.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Phentermine is sympathomimetic amine with pharmacologic 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 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 fraction of pound 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 in years, whereas the studies cited are restricted to few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Advanced arteriosclerosis, cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.Agitated states.Patients with history of drug abuse.During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).

DESCRIPTION SECTION.

DESCRIPTION. Phentermine hydrochloride, USP has the chemical name of ,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:Phentermine hydrochloride is 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) powder-filled capsules containing 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: corn starch, magnesium stearate, lactose anhydrous. In addition, the natural/blue capsules contain gelatin, D&C Red 28, and FD&C Blue 1; the yellow/yellow capsules contain gelatin, D&C Yellow 10, FD&C Red 3, and titanium dioxide; and the black/black capsules contain gelatin, FD&C Yellow 6, FD&C Blue 1, and FD&C Red 40. The imprinting ink for the natural/blue capsules and yellow/yellow capsules contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue Aluminum Lake, FD&C Red 40 Aluminum Lake, FD&C Blue Aluminum Lake, and D&C Yellow 10 Aluminum Lake. The imprinting ink for the black/black capsules contains: shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, yellow iron oxide, and dimethicone.b) pellet-filled capsules containing 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: sugar spheres, hypromellose, titanium dioxide, polyethylene glycol, polysorbate 80, FD&C Blue Aluminum Lake, FD&C Blue 1, and gelatin. The imprinting ink for the pellet-filled capsules contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue Aluminum Lake, FD&C Red 40 Aluminum Lake, FD&C Blue Aluminum Lake, and D&C Yellow 10 Aluminum Lake.. a) powder-filled capsules containing 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: corn starch, magnesium stearate, lactose anhydrous. In addition, the natural/blue capsules contain gelatin, D&C Red 28, and FD&C Blue 1; the yellow/yellow capsules contain gelatin, D&C Yellow 10, FD&C Red 3, and titanium dioxide; and the black/black capsules contain gelatin, FD&C Yellow 6, FD&C Blue 1, and FD&C Red 40. The imprinting ink for the natural/blue capsules and yellow/yellow capsules contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue Aluminum Lake, FD&C Red 40 Aluminum Lake, FD&C Blue Aluminum Lake, and D&C Yellow 10 Aluminum Lake. The imprinting ink for the black/black capsules contains: shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, yellow iron oxide, and dimethicone.. b) pellet-filled capsules containing 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: sugar spheres, hypromellose, titanium dioxide, polyethylene glycol, polysorbate 80, FD&C Blue Aluminum Lake, FD&C Blue 1, and gelatin. The imprinting ink for the pellet-filled capsules contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue Aluminum Lake, FD&C Red 40 Aluminum Lake, FD&C Blue Aluminum Lake, and D&C Yellow 10 Aluminum Lake.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Dosage should be individualized to obtain an adequate response with the lowest effective dose.. Exogenous Obesity. The usual adult dosage is 15 to 30 mg at approximately hours after breakfast for appetite control. Late evening medication should be avoided because of the possibility of resulting insomnia. Administration of one capsule (30 mg) daily has been found to be adequate in depression of the appetite for 12 to 14 hours.Phentermine is not recommended for use in patients 16 years of age and under.

DRUG ABUSE AND DEPENDENCE SECTION.

DRUG ABUSE AND DEPENDENCE. Phentermine is related chemically and pharmacologically to the amphetamines. Amphetamines and related stimulant drugs have been extensively abused, and the possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including drug as part of weight reduction program. 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.

GENERAL PRECAUTIONS SECTION.

General. Caution is to be exercised in prescribing phentermine hydrochloride for patients with even mild hypertension.Insulin requirements in diabetes mellitus may be altered in association with the use of phentermine and the concomitant dietary regimen.Phentermine 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.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Phentermine hydrochloride capsules are supplied as:30 mg powder-filled capsules, natural/blue; imprinted logo LANNETT on the cap and 1308 on the body, in bottles of 100 (NDC 0527-1308-01) and 1000 (NDC 0527-1308-10) capsules.30 mg powder-filled capsules, yellow/yellow; imprinted logo LANNETT on the cap and 1310 on the body, in bottles of 100 (NDC 0527-1310-01) and 1000 (NDC 0527-1310-10) capsules.30 mg powder-filled capsules, black/black; imprinted logo LANNETT on the cap and logo 0597 logo on the body, in bottles of 100 (NDC 0527-0597-01) and 1000 (NDC 0527-0597-10) capsules.30 mg pellet-filled capsules, blue/white; imprinted logo LANNETT on the cap and 1438 on the body, in bottles of 100 (NDC 0527-1438-01) and 1000 (NDC 0527-1438-10) capsules.. Storage. Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight, light-resistant container as defined in the USP, with child-resistant closure (as required).

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Phentermine hydrochloride is indicated as short-term (a few weeks) adjunct in regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index >= 30 kg/m2, or >= 27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes, hyperlipidemia).Below is chart of Body Mass Index (BMI) based on various heights and weights.BMI is calculated by taking the patients weight, in kilograms (kg), divided by the patients height, in meters (m), squared. Metric conversions are as follows: pounds 2.2 kg; inches 0.0254 meters.The limited usefulness of agents of this class (see CLINICAL PHARMACOLOGY) should be measured against possible risk factors inherent in their use such as those described below.. BMI Table.

NURSING MOTHERS SECTION.

Nursing Mothers. Because of the potential for serious adverse reactions in nursing infants, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

OVERDOSAGE SECTION.

OVERDOSAGE. Manifestations of acute overdosage with phentermine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, 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. Fatal poisoning usually terminates in convulsions and coma.Management of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with barbiturate. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard. Acidification of the urine increases phentermine excretion. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates phentermine overdosage.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Bottle Label 10544-593-28 Bottle Label.

PEDIATRIC USE SECTION.

Pediatric Use. Safety and effectiveness in pediatric patients have not been established.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Caution is to be exercised in prescribing phentermine hydrochloride for patients with even mild hypertension.Insulin requirements in diabetes mellitus may be altered in association with the use of phentermine and the concomitant dietary regimen.Phentermine 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 have not been performed with phentermine hydrochloride to determine the potential for carcinogenesis, mutagenesis or impairment of fertility.. Pregnancy. Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with phentermine hydrochloride. It is also not known whether phentermine hydrochloride can cause fetal harm when administered to pregnant woman or can affect reproductive capacity. Phentermine should be given to pregnant woman only if clearly needed.. Nursing Mothers. Because of the potential for serious adverse reactions in nursing infants, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.. Pediatric Use. Safety and effectiveness in pediatric patients have not been established.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with phentermine hydrochloride. It is also not known whether phentermine hydrochloride can cause fetal harm when administered to pregnant woman or can affect reproductive capacity. Phentermine should be given to pregnant woman only if clearly needed.

STORAGE AND HANDLING SECTION.

Storage. Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight, light-resistant container as defined in the USP, with child-resistant closure (as required).

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with phentermine hydrochloride. It is also not known whether phentermine hydrochloride can cause fetal harm when administered to pregnant woman or can affect reproductive capacity. Phentermine should be given to pregnant woman only if clearly needed.

WARNINGS SECTION.

WARNINGS. Phentermine hydrochloride capsules are indicated only as short-term monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with phentermine and any other drug products for weight loss, including selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. Therefore, coadministration of these drug products for weight loss is not recommended.Primary Pulmonary Hypertension (PPH)--a rare, frequently fatal disease of the lungs--has been reported to occur in patients receiving combination of phentermine with fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; there have been rare cases of PPH in patients who reportedly have taken phentermine alone. The initial symptom of PPH is usually dyspnea. Other initial symptoms include: angina pectoris, syncope or lower extremity edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Treatment should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema.Valvular Heart Disease: Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricuspid valves, has been reported in otherwise healthy persons who had taken combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.Tolerance to the anorectic effect usually develops within few weeks. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.Phentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving motor vehicle; the patient should therefore be cautioned accordingly.. Usage with Alcohol. Concomitant use of alcohol with phentermine may result in an adverse drug interaction.