Label: DIETHYLPROPION HYDROCHLORIDE tablet

Diethylpropion hydrochloride is available for oral administration in immediate-release tablets containing 25 mg diethylpropion hydrochloride. The inactive ingredients in each immediate-release tablet are: crospovidone, lactose anhydrous, magnesium stearate, starch pregelatinized and tartaric acid. Diethylpropion hydrochloride is a sympathomimetic agent. The chemical name for diethylpropion hydrochloride is 1-phenyl-2-diethylamino-1-propanone hydrochloride.

Its chemical structure is:

Diethylpropion hydrochloride is a sympathomimetic amine with some pharmacologic activity similar to that of the prototype drugs of this class used in obesity, the amphetamines. Actions include some central nervous system stimulation and elevation of blood pressure. Tolerance has 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. For example, other central nervous system actions or metabolic effects may be involved. 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 averages some fraction of a pound a week. However, individual weight loss may vary substantially from patient to patient. 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 relationship, 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 most studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone is unknown. Diethylpropion is rapidly absorbed from the GI tract after oral administration and is extensively metabolized through a complex pathway of biotransformation involving N-dealkylation and reduction. Many of these metabolites are biologically active and may participate in the therapeutic action of diethylpropion hydrochloride. Due to the varying lipid solubilities of these metabolites, their circulating levels are affected by urinary pH. Diethylpropion and/or its active metabolites are believed to cross the blood-brain barrier and the placenta.

Diethylpropion and its metabolites are excreted mainly by the kidney. It has been reported that between 75-106% of the dose is recovered in the urine within 48 hours after dosing. Using a phosphorescence assay that is specific for basic compounds containing a benzoyl group, the plasma half-life of the aminoketone metabolites is estimated to be between 4 to 6 hours.

The extended-release characteristics of the diethylpropion hydrochloride 75 mg formulation have been demonstrated by studies in humans in which plasma levels of diethylpropion-related materials were measured by phosphorescence analysis. Plasma levels obtained with the 75 mg diethylpropion hydrochloride formulation administered once daily indicated a more gradual release than an immediate-release formulation (three 25 mg tablets given in a single dose).

The diethylpropion hydrochloride 75 mg extended -release formulation has not been shown superior in effectiveness to the same dosage of the immediate-release formulation (one 25 mg tablet three times daily). After administration of a single dose of the diethylpropion hydrochloride 75 mg formulation (one 75 mg extended -release tablet) or diethylpropion hydrochloride solution (75 mg dose) in a crossover study using normal human subjects, the amount of parent compound and its active metabolites recovered in the urine within 48 hours for the two dosage forms were not statistically different.

Diethylpropion hydrochloride 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 in patients with an initial body mass index (BMI) of 30 kg/m 2or higher and who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone. Below is a chart of 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 divided by 2.2 = kg; inches x 0.0254 = meters.

The 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. Diethylpropion hydrochloride is indicated for use as monotherapy only.

Pulmonary hypertension, advanced arteriosclerosis, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma, severe hypertension. (See PRECAUTIONS.)

Agitated states.

Patients with a history of drug abuse.

Use in combination with other anorectic agents is contraindicated.

During or within 14 days following the administration of monoamine oxidase inhibitors, hypertensive crises may result.

Diethylpropion hydrochloride 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 diethylpropion, was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than 3 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, diethylpropion hydrochloride 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. Valvulopathy has been very rarely reported with diethylpropion hydrochloride monotherapy, but the causal relationship remains uncertain.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 diethylpropion hydrochloride treatment. Diethylpropion hydrochloride 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 diethylpropion hydrochloride should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (e.g., weight loss of at least 4 pounds, or as determined by the physician and patient).

Diethylpropion hydrochloride is not recommended for patients who used any anorectic agents within the prior year.

If tolerance develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued. Diethylpropion hydrochloride 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.

Prolonged use of diethylpropion hydrochloride may induce dependence with withdrawal syndrome on cessation of therapy. Hallucinations have occurred rarely following high doses of the drug. Several cases of toxic psychosis have been reported following the excessive use of the drug and some have been reported in which the recommended dose appears not to have been exceeded. Psychosis abated after the drug was discontinued.

When central nervous system active agents are used, consideration must always be given to the possibility of adverse interactions with alcohol.

Cardiovascular:Precordial pain, arrhythmia (including ventricular), ECG changes, tachycardia, elevation of blood pressure, palpitation and rare reports of pulmonary hypertension. Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine, both independently and especially when used in combination, have been reported. Valvulopathy has been very rarely reported with diethylpropion hydrochloride monotherapy, but the causal relationship remains uncertain.

Central Nervous System:In a few epileptics an increase in convulsive episodes has been reported; rarely psychotic episodes at recommended doses; dyskinesia, blurred vision, overstimulation, nervousness, restlessness, dizziness, jitteriness, insomnia, anxiety, euphoria, depression, dysphoria, tremor, mydriasis, drowsiness, malaise, headache, and cerebrovascular accident

Gastrointestinal:Vomiting, diarrhea, abdominal discomfort, dryness of the mouth, unpleasant taste, nausea, constipation, other gastrointestinal disturbances

Allergic:Urticaria, rash, ecchymosis, erythema

Endocrine:Impotence, changes in libido, gynecomastia, menstrual upset

Hematopoietic System:Bone marrow depression, agranulocytosis, leukopenia

Miscellaneous:A variety of miscellaneous adverse reactions has been reported by physicians. These include complaints such as dysuria, dyspnea, hair loss, muscle pain, increased sweating, and polyuria.

Diethylpropion hydrochloride is a schedule IV controlled substance. Diethylpropion hydrochloride has some chemical and pharmacologic similarities to the amphetamines and other related stimulant drugs that have been extensively abused. There have been reports of subjects becoming psychologically dependent on diethylpropion. The possibility of abuse should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. Abuse of amphetamines and related drugs may be associated with varying degrees of psychologic dependence and social dysfunction which, in the case of certain drugs, may be severe. 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 intoxication is psychosis, often clinically indistinguishable from schizophrenia.

Manifestations of acute overdosage include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, and mydriasis.

Fatigue and depression usually follow the central stimulation.

Cardiovascular effects include tachycardia, arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Overdose of pharmacologically similar compounds has resulted in convulsions, coma and death.

The reported oral LD 50for mice is 600 mg/kg, for rats is 250 mg/kg and for dogs is 225 mg/kg.

Management of acute diethylpropion hydrochloride intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Intravenous phentolamine (Regitine ®) has been suggested on pharmacologic grounds for possible acute, severe hypertension, if this complicates diethylpropion hydrochloride overdosage.

Diethylpropion hydrochloride immediate-release:

One immediate-release 25 mg tablet three times daily, one hour before meals, and in midevening if desired to overcome night hunger.

25 mg immediate-release tablets in bottles of 100.

NDC 68071-3836-1

Each white to off white, round flat tablets debossed “K 44” on one side and plain on the other side.

Keep tightly closed. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Rx only

Manufactured by:

KVK-TECH, INC.

110 Terry Dr. Suite 200

Newtown, PA 18940-1850

Item ID # 6129/04 10/2021

Manufacturer’s Code: 10702