Trimethobenzamide

Risk Summary

The limited available data with trimethobenzamide in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. No adverse developmental effect was observed in animal reproduction studies with administration of trimethobenzamide hydrochloride during organogenesis in pregnant rats at doses 0.16 and 0.8 times the recommended human dose (RHD) and in pregnant rabbits at doses 1.6 times the RHD [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Reproduction studies with trimethobenzamide hydrochloride were conducted in rats and rabbits following administration of trimethobenzamide hydrochloride during organogenesis and no adverse developmental effect was observed in either species. The only effects observed were an increased percentage of embryonic resorptions or stillborn pups in rats administered 20 mg/kg and 100 mg/kg (0.16 and 0.8 times the RHD of 1200 mg/day, based on body surface area) and increased resorptions in rabbits receiving 100 mg/kg (1.6 times the RHD of 1200 mg/day, based on body surface area). In each study, these adverse effects were attributed to one or two dams.

Risk Summary

There is no information on the presence of trimethobenzamide in human milk, the effects of trimethobenzamide on the breastfed infant or the effects of trimethobenzamide on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of trimethobenzamide to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for trimethobenzamide and any potential adverse effects on the breastfed infant from trimethobenzamide or from the underlying maternal condition.

Oral administration

The following adverse reactions from voluntary reports or clinical studies have been reported with trimethobenzamide. Because many of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous system disorders: Parkinson-like symptoms, coma, convulsions, opisthotonos, dizziness, drowsiness, headache

Psychiatric disorders: disorientation, depression of mood

Eye disorders: blurred vision

Hematologic disorders: blood dyscrasias

Hepatobiliary disorders: jaundice

Immune system disorders: hypersensitivity, including angioedema and allergic-type skin reactions

Gastrointestinal disorders: diarrhea

Musculoskeletal disorders: muscle cramps

Intramuscular administration

There have been reports of hypersensitivity reactions and Parkinson-like symptoms. There have been instances of hypotension reported following parenteral administration to surgical patients. There have been reports of blood dyscrasias, blurring of vision, coma, convulsions, depression of mood, diarrhea, disorientation, dizziness, drowsiness, headache, jaundice, muscle cramps and opisthotonos. If these occur, the administration of the drug should be discontinued. Allergic-type skin reactions have been observed; therefore, the drug should be discontinued at the first sign of sensitization. While these symptoms will usually disappear spontaneously, symptomatic treatment may be indicated in some cases.