Toxicology of the combination lofexidine/hydrochlorothiazide.
The toxicity and side-effects of the antihypertensive and diuretic combination 2-[1-(2,6-dichlorphenoxy)-ethyl-2-imidazoline-hydrochloride (lofexidine, Lofetensin and Loxacor) hydrochlorothiazide were studied in toxicity and teratogenicity tests and the possibility of interactions was investigated. In terms of lofexidine, there was no evidence of any adverse interactions with hydrochlorothiazide either following a single, oral administration to rats and mice or following short-term and long-term repeated oral dosing of rats and dogs. In the subchronic and chronic toxicity studies it was actually found that the familiar, unwanted sedative effect of lofexidine failed to occur when the combined preparation was given. With repeated oral administration to rats and dogs definite drug-related toxic findings, such as a reduction in serum potassium, mineralization of a few organs and crystal formation in the urine, only occurred at dose levels far above the therapeutic dose. The results of these studies along with historical data on the individual components would suggest a lack of carcinogenic potential for this combination. No teratogenic or embryotoxic effects were noted in rats or rabbits.
D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004285:Dogs; D004338:Drug Combinations; D005260:Female; D006852:Hydrochlorothiazide / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D004338:Drug Combinations; D013723:Teratogens; D006852:Hydrochlorothiazide; D003000:Clonidine; C025655:lofexidine