Lindane

Pregnancy Category C

All pregnancies have a risk of birth defect, loss, or other adverse event regardless of drug exposure. Predictions of fetal risk from drug exposure rely heavily on animal data. However, animal studies may fail to predict effects in humans or may overstate such risks. Even if human data are available, the data may not be sufficient to determine whether there is an increased risk to the fetus, and individual reports of adverse outcomes in pregnancy in association with a drug may not reflect a causal relationship.

Lindane Lotion should be given to pregnant women only if clearly needed. There are no adequate and well-controlled studies of lindane Lotion in pregnant women. There are no known maternal or fetal health risks if the scabies is not treated. Lindane is lipophilic and may accumulate in the placenta. There has been a single case report of a stillborn infant following multiple maternal exposures to lindane during pregnancy. The relationship of the maternal exposures to the fetal outcome is unknown.

Animal data suggest that lindane exposure of the fetus may increase the likelihood of neurologic developmental abnormalities (see below), based on findings at systemic exposures close to that expected in humans when lindane lotion is used to treat scabies. The immature central nervous system (as in the fetus) may have increased susceptibility to the effects of the drug.

Data

When rats received lindane in the diet from day 6 of gestation through day 10 of lactation, reduced pup survival, decreased pup weight and decreased weight gains during lactation, increased motor activity and decreased motor activity habituation were seen in pups at 5.6 mg/kg (2 times the estimated human exposure) but not at 1.2 mg/kg. An increased number of stillborn pups was seen at 8 mg/kg, and increased pup mortality was seen at 5.6 mg/kg. No gross abnormalities were seen in this study or in a study in which rabbits received up to 20 mg/kg lindane by gavage on gestation day 6–18 (up to 10 times the human exposure on a body surface area comparison and assuming 50% rabbit oral bioavailability and 10% human bioavailability).

Lindane is lipophilic and is present in human breast milk, but exact quantities are not known. There may be a risk of toxicity if lindane is ingested from breast milk, or from skin absorption from mother to baby in the course of breast-feeding when lindane lotion is applied topically to the chest area. Nursing mothers who require treatment with lindane lotion should be advised of the potential risks and be counseled to avoid large areas of skin-to-skin contact with the infant while lindane Lotion is applied, as well as to interrupt breast-feeding, with expression and discarding of milk, for at least 24 hours following use.

Although no studies have been conducted with lindane, numerous long-term feeding studies have been conducted in mice and rats to evaluate the carcinogenic potential of the technical grade of hexachlorocyclohexane as well as the alpha, beta, gamma (lindane) and delta isomers. Both oral and topical applications have been evaluated. Increased incidences of neoplasms were not clearly related to administration of lindane. The results of mutagenicity tests in bacteria do not indicate that lindane is mutagenic. Lindane did not cause sister chromatid exchange in an in vivo assay. The number of spermatids in the testes of rats 2 weeks after oral administration of a single dose of 30 mg/kg body weight (12 times the estimated human exposure for scabies on a body surface area comparison and assuming 50% rat oral bioavailability and 10% human bioavailability) was significantly reduced compared to the control rats.

Lindane has been reported to cause central nervous system stimulation ranging from dizziness to seizures. Although seizures were almost always associated with ingestion or misuse of the product (to include repeat treatment), seizures and deaths have been reported when lindane lotion was used according to directions. Irritant dermatitis from contact with this product has also been reported.

Postmarketing Experience

The following adverse reactions reflect additional postmarketing experience of lindane Lotion. These events include alopecia, dermatitis, headache, pain, paresthesia, pruritus and urticaria. The relationship of some of these events to lindane therapy is unknown.