Animal Toxicology Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes at unbound tadalafil exposure of 2-to 33-fold above the human exposure (AUCs) at the MRHD of 20 mg. In dogs, an increased incidence of disseminated arteritis was observed in 1-and 6-month studies at unbound tadalafil exposure of 1-to 54-fold above the human exposure (AUC) at the MRHD of 20 mg. In a 12-month dog study, no disseminated arteritis was observed, but 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately 14-to 18-fold the human exposure at the MRHD of 20 mg. The abnormal blood-cell findings were reversible within 2 weeks upon removal of the drug. Pregnancy, Nursing Mothers, and Pediatric Use CIALIS is not indicated for use in newborns, children, or women. Tadalafil and/ or its metabolites cross the placenta, resulting in fetal exposure in rats. Tadalafil and/ or its metabolites were secreted into the milk in lactating rats at concentrations approximately 2.4-fold greater than found in the plasma. Following a single-oral dose of 10 mg/ kg, approximately 0.1% of the total radioactive dose was excreted into the milk within 3 hours. It is not known if tadalafil and/ or its metabolites is excreted in human breast milk. Use of tadalafil in nursing mothers is not recommended. Pregnancy Category B ? There was no evidence of teratogenicity, embryotoxicity, or fetotoxicity in rat or mouse fetuses that received up to 1000 mg/ kg/ day during the major organ development. Plasma exposure at this dose is approximately 11-fold greater than the AUC values for unbound tadalafil in humans given the MRHD of 20 mg. In a rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/ kg, there was a reduction in postnatal survival of pups. The no-observed-effect-level (NOEL) for maternal toxicity was 200 mg/ kg/ day and for developmental toxicity was 30 mg/ kg/ day, which gives approximately 16-and 10-fold exposure multiples, respectively, of the human AUC for the MRHD dose of 20 mg. There are no adequate and well-controlled studies of tadalafil in pregnant women. Geriatric Use Approximately 25% of patients in the primary efficacy and safety studies of tadalafil were greater than 65 years of age. No overall differences in efficacy and safety were observed between older and younger patients. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered (see Special Populations under CLINICAL PHARMACOLOGY). | ||||
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