Carvedilol nonclinical toxicology: Difference between revisions
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==Nonclinical Toxicology== | ==Nonclinical Toxicology== | ||
===Carcinogenesis, Mutagenesis, Impairment of Fertility=== | |||
In 2-year studies conducted in rats given carvedilol at doses up to 75 mg/kg/day (12 times the MRHD when compared on a mg/m2 basis) or in mice given up to 200 mg/kg/day (16 times the MRHD on a mg/m2 basis), carvedilol had '''no carcinogenic effect.''' | In 2-year studies conducted in rats given carvedilol at doses up to 75 mg/kg/day (12 times the MRHD when compared on a mg/m2 basis) or in mice given up to 200 mg/kg/day (16 times the MRHD on a mg/m2 basis), carvedilol had '''no carcinogenic effect.''' | ||
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At doses ≥200 mg/kg/day ( ≥ 32 times the MRHD as mg/m2) carvedilol was toxic to adult rats (sedation, reduced weight gain) and was associated with a reduced number of successful matings, prolonged mating time, significantly fewer corpora lutea and implants per dam, and complete resorption of 18% of the litters. | At doses ≥200 mg/kg/day ( ≥ 32 times the MRHD as mg/m2) carvedilol was toxic to adult rats (sedation, reduced weight gain) and was associated with a reduced number of successful matings, prolonged mating time, significantly fewer corpora lutea and implants per dam, and complete resorption of 18% of the litters. | ||
The '''no-observed-effect dose''' level for overt toxicity and impairment of fertility was 60 mg/kg/day (10 times the MRHD as mg/m2).<ref name="dailymed.nlm.nih.gov">{{Cite web | last = |first = | title = COREG (CARVEDILOL) TABLET, FILM COATED [GLAXOSMITHKLINE LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c57982f2-c7da-488a-7ea9-b9609439ac68#nlm34089-3 | publisher = | date = | accessdate = }}</ref> | The '''no-observed-effect dose''' level for overt toxicity and impairment of fertility was 60 mg/kg/day (10 times the MRHD as mg/m2).<ref name="dailymed.nlm.nih.gov">{{Cite web | last = |first = | title = COREG (CARVEDILOL) TABLET, FILM COATED [GLAXOSMITHKLINE LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c57982f2-c7da-488a-7ea9-b9609439ac68#nlm34089-3 | publisher = | date = | accessdate = }}</ref> | ||
==References== | ==References== | ||
{{Reflist}} | {{Reflist}} | ||
Revision as of 21:53, 20 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
In 2-year studies conducted in rats given carvedilol at doses up to 75 mg/kg/day (12 times the MRHD when compared on a mg/m2 basis) or in mice given up to 200 mg/kg/day (16 times the MRHD on a mg/m2 basis), carvedilol had no carcinogenic effect.
Carvedilol was negative when tested in a battery of genotoxicity assays, including the Ames and the CHO/HGPRT assays for mutagenicity and the in vitro hamster micronucleus and in vivo human lymphocyte cell tests for clastogenicity.
At doses ≥200 mg/kg/day ( ≥ 32 times the MRHD as mg/m2) carvedilol was toxic to adult rats (sedation, reduced weight gain) and was associated with a reduced number of successful matings, prolonged mating time, significantly fewer corpora lutea and implants per dam, and complete resorption of 18% of the litters. The no-observed-effect dose level for overt toxicity and impairment of fertility was 60 mg/kg/day (10 times the MRHD as mg/m2).[1]
References
Adapted from the FDA Package Insert.