Reserpine nonclinical toxicology

Reserpine
Reserpine® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings
Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages
Clinical Trials on Reserpine
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal Tumorigenicity

Rodent studies have shown that reserpine is an animal tumorigen, causing an increased incidence of mammary fibroadenomas in female mice, malignant tumors of the seminal vesicles in male mice, and malignant adrenal medullary tumors in male rats. These findings arose in 2-year studies in which the drug was administered in the feed at concentrations of 5 to 10 ppm – about 100 to 300 times the usual human dose. The breast neoplasms are thought to be related to reserpine’s prolactin-elevating effect. Several other prolactin-elevating drugs have also been associated with an increased incidence of mammary neoplasia in rodents.

The extent to which these findings indicate a risk to humans is uncertain. Tissue culture experiments show that about one third of human breast tumors are prolactin-dependent in vitro, a factor of considerable importance if the use of the drug is contemplated in a patient with previously detected breast cancer. The possibility of an increased risk of breast cancer in reserpine users has been studied extensively; however, no firm conclusion has emerged. Although a few epidemiologic studies have suggested a slightly increased risk (less than twofold in all studies except one) in women who have used reserpine, other studies of generally similar design have not confirmed this. Epidemiologic studies conducted using other drugs (neuroleptic agents) that, like reserpine, increase prolactin levels and therefore would be considered rodent mammary carcinogens have not shown an association between chronic administration of the drug and human mammary tumorigenesis. While long-term clinical observation has not suggested such as association, the available evidence is considered too limited to be conclusive at this time. An association of reserpine intake with pheochromocytoma or tumors of the seminal vesicles has not been explored.

Pregnancy Category C

Reserpine administered parenterally has been shown to be teratogenic in rats at doses up to 2 mg/kg and to have an embryocidal effect in guinea pigs given dosages of 0.5 mg daily.

There are no adequate and well-controlled studies of reserpine in pregnant women. Reserpine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Reserpine crosses the placental barrier, and increased respiratory tract secretions, nasal congestion, cyanosis, and anorexia may occur in neonates of reserpine-treated mothers.

Nursing Mothers

Reserpine is excreted in maternal breast milk, and increased respiratory tract secretions, nasal congestion, cyanosis, and anorexia may occur in breast-fed infants. Because of the potential for adverse reactions in nursing infants and the potential for tumorigenicity shown for reserpine in animal studies, 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.

Pediatric Use

Safety and effectiveness in children have not been established by means of controlled clinical trials, although there is experience with the use of reserpine in children (see DOSAGE AND ADMINISTRATION.) Because of adverse effects such as emotional depression and lability, sedation, and stuffy nose, reserpine is not usually recommended as a step-2 drug in the treatment of hypertension in children