Tenuate (Diethylpropion)

TENUATE® TENUATE® DOSPAN® Hoechst Marion Roussel Diethylpropion HCl Anorexiant

Action and Clinical

Diethylpropion is a psychomotor stimulant with anorectic, sympathomimetic and other effects similar to those of amphetamines. As with all other drugs of this class in which the phenomenon has been studied, the initial rate of weight loss decreases until a plateau is reached; a regain of weight thereafter even though drug administration is continued has been reported. As with similar drugs, rebound weight gain also may occur after discontinuation of diethylpropion.

Indications And Clinical Uses:

A psychomotor stimulant used as an adjunct in the short-term (i.e., a few weeks) to continued dietary treatment in the medical management of obesity, in patients who have not responded to an appropriate weight reducing regimen (diet and/or exercise) alone. Diethylpropion is recommended only for obese patients with an initial body mass index ³ 30 kg/m.

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 kg, divided by the patient’s height in m and squared. Metric conversions are as follows: pounds (lbs)/2.2=kilograms (kg); feet (ft)´0.3048=meters (m); inches´0.0254=meters (m).

When prescribing anorectic agents it should be borne in mind that the role of these drugs in the management of obesity is strictly limited, since patients treated with anorectics lose, on average, only a fraction of a pound per week more than those who are on a weight reducing diet alone. Furthermore, the rate of weight loss tends to decrease within a few weeks and a plateau is reached. Prolonged administration of diethylpropion should also be strictly avoided since it can lead to drug dependence and abuse (see Warnings). Therefore, even short-term use of an anorectic drug is not recommended unless a carefully supervised weight reduction regimen by itself is not successful.

Contra-Indications:

Diethylpropion is contraindicated: during therapy with monoamine oxidase inhibitors or within 14 days following withdrawal of these agents, hypertensive crisis may result; in patients with pulmonary artery hypertension; in patients with glaucoma; in patients with hyperthyroidism; in patients with advanced arteriosclerosis; in patients with severe hypertension; in patients with known heart murmur or valvular heart disease; in patients with agitated states; in patients with known hypersensitivity or idiosyncrasy to sympathomimetic amines; in emotionally unstable individuals who are known to be susceptible to or have a history of drug abuse; in combination use with other anorectic agents.WarningWarnings

Warnings in Clinical States:

Primary Pulmonary Hypertension: Anorexigens, including diethylpropion, increase the risk of developing primary pulmonary hypertension, an often fatal disorder.

An epidemiological study has indicated that use of anorexigens, including diethylpropion, for longer than 3 months was associated with a 23-fold increase in the risk of developing Primary Pulmonary Hypertension (PPH). There was no significant increase in risk for persons who had used these agents for 3 months or less. Obesity itself (body mass index ³ 30 kg/m).

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, treatment should be immediately discontinued, and the patient should be evaluated for the possible presence of PPH.

Valvular Heart Disease: Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing risk factors include use for extended period of time, higher than recommended dose, and/or use in combination with other anorectic agents.

Valvular heart disease has been very rarely reported with diethylpropion 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 pre-existing valvular heart diseases or pulmonary hypertension prior to initiation of diethylpropion treatment. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur.

Drug Dependence: There is a good correlation between a drug’s ability to act as a positive reinforcer in animals and its abuse potential in man. Diethylpropion has been shown to serve as a positive reinforcer in various self-administration studies performed in animals.

Furthermore, experience with anorectic drugs with amphetamine-like properties such as diethylpropion has established that prolonged use of these drugs can produce tolerance, severe psychological dependence and may lead to extensive abuse. There have been a significant number of reports of abuse of diethylpropion in the last several years. This should be kept in mind when assessing the desirability of using the drug and caution should be exercised not to use the drug in individuals whose histories suggest they may develop dependence or increase the dosage on their own initiative.

If psychological dependence occurs, gradual withdrawal of the medication is recommended. Abrupt cessation following prolonged high dosage may result in extreme fatigue and mental depression and changes in the sleep EEG. Drug abuse may lead to moderate to severe manifestations of chronic intoxication including marked insomnia, irritability, hyperactivity, personality changes and even psychosis.

  • Tolerance: In most patients, weight loss during treatment with diethylpropion plateaus after a few weeks. If tolerance develops discontinuation of medication is indicated rather than an increase in the dose. The recommended dose should not be exceeded in an attempt to increase the effect.
  • Pregnancy: Diethylpropion should not be used in women of childbearing potential unless in the opinion of the prescribing physician the potential benefits of drug therapy outweigh the possible risks to mother and fetus.
  • Children: Diethylpropion is not recommended for use in children under 12 years of age.
  • Geriatrics: Diethylpropion is not recommended for the elderly.
  • General: Diethylpropion is not recommended for patients who used any anorectic agents within the prior year.
  • Occupational Hazards: Diethylpropion may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle.

Precautions:

Diethylpropion should be used with caution in patients with mild cardiovascular disease or hypertension, and regular monitoring of cardiovascular function and blood pressure is indicated in such patients receiving diethylpropion. Diethylpropion should not be used in patients with severe cardiovascular disease including arrhythmias or hypertension.

Diethylpropion is not recommended in patients with known heart murmur or valvular diseases (see Contraindications).

Prolonged use of diethylpropion may induce dependence with withdrawal syndrome on cessation of therapy (see Warnings). 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 a very small number have been reported in which the recommended dose appears not to have been exceeded. Psychosis abated after the drug was discontinued.

Reports also suggest that diethylpropion may increase the incidence of convulsions in some epileptic patients. Therefore, caution is required if the drug is administered to epileptic patients. Epileptics receiving diethylpropion should be carefully monitored. Titration of dose or discontinuance of the drug may be necessary.

Occupational Hazards: Driving a Vehicle of Performing Other Hazardous Tasks: See Warnings.

Drug Interactions: Diethylpropion is contraindicated with MAOIs (see Contraindications).

Efficacy of diethylpropion with other anorectic agents has not been studied and the combined use may have the potential for serious cardiac problems; therefore concomitant use with other anorectic agents is contraindicated.

Arrhythmias have been associated with some sympathomimetic agents given concurrently with general anesthetics; therefore, caution should be used during general anesthesia in patients receiving diethylpropion.

Diethylpropion may alter the effect of other drugs which act on the CNS. Insulin requirements in diabetes mellitus may be altered in association with the use of diethylpropion and the concomitant dietary regimen. Diethylpropion may decrease the hypotensive effect of guanethidine. In addition, drugs of this class may potentiate the pressor effects of exogenous catecholamines.

Pregnancy: Diethylpropion should not be used during pregnancy, unless in the opinion of the prescribing doctor, the potential benefits outweigh the potential risks (see Warnings).

Isolated spontaneous reports of congenital malformations have been recorded in humans, but no causal relationship to diethylpropion has been established.

Use during pregnancy may result in withdrawal symptoms in the neonate.

No evidence of teratogenicity has been observed in animal studies. Reproduction studies in rats showed no harm to the fetus at doses up to 9 times the human dose. Animal reproduction studies have revealed no evidence of impairment of fertility at doses up to 60 mg/kg/day. Higher doses may cause maternal and/or embryo toxicity.

Lactation: It is not known if diethylpropion and/or its metabolites pass into human milk. Use in a nursing woman is not recommended.

Adverse Reactions:

The most frequently encountered side effects of diethylpropion are insomnia, nervousness, dizziness, anxiety, agitation and dry mouth. An epidemiological study has indicated that use of anorexigens for longer than 3 months was associated with an increase in the risk of developing Primary Pulmonary Hypertension (PPH) (see Warnings).

CNS: dyskinesia, blurred vision, overstimulation, nervousness, restlessness, dizziness, jitteriness, insomnia, anxiety, euphoria, dysphoria and occasionally depression, tremor, mydriasis, drowsiness, malaise, headache, cerebrovascular accident, and psychotic episodes. Increase in convulsive disorders has been reported.

Cardiovascular: tachycardia, precordial pain, arrhythmias (including ventricular), palpitation, increased blood pressure, electrocardiogram changes. One published report described T wave changes in the ECG of a healthy young male after ingestion of diethylpropion. There have been reports of primary pulmonary hypertension associated with the use of diethylpropion (see Warnings).

Valvular heart disease has been very rarely reported with diethylpropion but the causal relationship remains uncertain.

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

Allergic: urticaria, rash, ecchymosis and erythema.

Endocrine: impotence, dysmenorrhea, changes in libido, menstrual upset and gynecomastia.

Drug Abuse and Dependence: There have been reports of subjects becoming psychologically dependent on diethylpropion.

Other: dyspnea, hair loss, muscle pain, dysuria, polyuria, bone marrow depression, leukopenia, agranulocytosis and increased sweating.

Symptoms And Treatment Of Overdose:

Clinical manifestations of diethylpropion intoxication are as follows: restlessness, tremor, hyperreflexia, nervousness and irritability, insomnia, rapid respiration, confusion, assaultiveness, hallucinations, and panic states. Mydriasis has been observed. Convulsions and tachycardia are frequently present. Exhaustion, drowsiness, fatigue or depression usually follow central stimulation, and coma may occur. Cardiovascular effects may include arrhythmias, changes in blood pressure and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Overdose has resulted in death.

Management of acute intoxication is largely symptomatic. It includes gastric lavage if possible, and sedation with a barbiturate may be desirable. Experience with peritoneal dialysis or hemodialysis is not sufficient to permit a recommendation at this time.

Dosage And Administration:

Adults: One 25 mg tablet may be administered 3 times daily, 1 hour before meals. Alternatively, one 75 mg sustained release tablet may be given once daily, in midmorning. Administration should not be extended beyond a period of 4 weeks. The least amount feasible should be prescribed or dispensed at one time (not to exceed a 2-week supply) in order to minimize the possibility of abuse.

Diethylpropion should be used for duration of no more than a few weeks (see Warnings).

Availability And Storage:

Tenuate: Each white tablet contains: diethylpropion HCl 25 mg. Nonmedicinal ingredients: lactose, magnesium stearate, talc and tartaric acid. Bottles of 100.

Tenuate Dospan: Each capsule-shaped, continuous-release, white tablet contains: diethylpropion HCl 75 mg. Nonmedicinal ingredients: carboxypolymethylene, mannitol, povidone, tartaric acid and zinc stearate. Bottles of 100 and 250. Cartons of 30 strip packed tablets.

Store between 15 and 30°C.

TENUATE® TENUATE® DOSPAN® Hoechst Marion Roussel Diethylpropion HCl Anorexiant

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