When tolerance to the "anorectic" effect develops, the maximum recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.
Fenfluramine differs in its pharmacological profile from other "anorectic" drugs with which the prescribing practitioner may be familiar. Correspondingly, there are possible adverse effects not associated with other "anorectics"; such effects include those of diarrhea, sedation, and depression. The possibility of these effects should be weighed against the possible advantage of decreased central nervous system stimulation and/or abuse potential.
There have been four cases of pulmonary hypertension reported in association with fenfluramine use. Two cases were apparently reversible after discontinuation of fenfluramine, but evidence of pulmonary hypertension recurred in one of these patients upon rechallenge with fenfluramine. A third patient was initially improved with nifedipine treatment, but was noted to have increased pulmonary arterial pressure again at a four month follow up visit. Finally, an irreversible and fatal case of pulmonary hypertension has been reported in a patient who had seven 1-month courses of fenfluramine in the twelve years prior to death. Patients taking fenfluramine should be advised to report immediately any deterioration in exercise tolerance.
Use only with caution in hypertension, with monitoring of blood pressure, since evidence is insufficient to rule out a possible adverse effect on blood pressure in some hypertensive patients. The drug is not recommended in severely hypertensive patients. The drug is not recommended for patients with symptomatic cardiovascular disease including arrhythmias.
Caution should be exercised in prescribing fenfluramine for patients with a history of mental depression. Further depression of mood may become evident while the patient is on fenfluramine or following withdrawal of fenfluramine. Symptoms of depression occurring immediately following abrupt withdrawal can be readily controlled by reinstituting Fenfluramine HCl, followed by a gradual tapering off of the daily dose.
Information for the Patient
Fenfluramine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle (see ADVERSE REACTIONS); the patient should be cautioned accordingly. Patient should also be advised to avoid alcoholic beverages while taking Fenfluramine HCl.
No carcinogenic studies or mutagenic studies have been undertaken with this drug.
Pregnancy Category C
Fenfluramine HCl was shown to produce a questionable embryotoxic effect in rats and a reduced conception rate when given in a dose of 20 times the human dose. However, additional reproduction studies in rats, rabbits, mice, and monkeys at doses up to, respectively, 5 times, 20 times, 1 time, and 5 times the human dose yielded negative results.
There are no adequate and well-controlled studies in pregnant women. Fenfluramine HCl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
The effect of fenfluramine during labor or delivery on the mother and the fetus is unknown. The effect on later growth, development, and functional maturation of the child is unknown.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when fenfluramine is administered to a nursing mother.
Safety and effectiveness in children below the age of 12 years has not been established.