1. Clonidine HCl was not cancer causing when carried out in the diet of rats (for as much as 132 weeks) or computer mice (for approximately 78 weeks) at doses of up to 1620 (male rats), 2040 (female rats), or 2500 (mice) mcg/kg/day. These dosages are about 20, 25, and 15 times, specifically, the maximum recommended human dose (MRHD) of 0.4 mg/day on a mg/m2 basis.

    Fertility of male or women rats was unaffected by clonidine HCl dosages as high as 150 mcg/kg/day (about 3 times the MRDHD on a mg/m2 basis). In a separate experiment, fertility of women rats seemed detrimentally influenced at dose levels of 500 and also 2000 mcg/kg/day (10 as well as 40 times the MRHD on a mg/m2 basis).

    In several studies with dental clonidine hydrochloride, a dose-dependent increase in the incidence as well as intensity of spontaneous retinal weakening was viewed in albino rats treated for 6 months or longer. Cells distribution studies in dogs as well as monkeys showed a concentration of clonidine in the choroid. In combination with amitriptyline, clonidine hydrochloride management led to the development of corneal sores in rats within 5 days.

    In view of the retinal deterioration viewed in rats, eye exams were carried out during clinical tests in 908 adult individuals before, and regularly after, the beginning of clonidine treatment for hypertension. In 353 of these 908 patients, the eye exams were performed over moments of 24 months or longer. Except for some dry skin of the eyes, no drug-related unusual ophthalmological searchings for were tape-recorded and, according to specialized examinations such as electroretinography and macular dazzle, retinal function was the same.