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reproductive performance or reproductive organ morphology in male or female rats given oral doses of tadalafil up to 400 mg kg day a dose producing AUCs for unbound tadalafil of 14 fold for males or 26 fold for females the exposures observed in human males given the MRHD of 20 mg In beagle dogs given tadalafil daily for 3 to 12 months there was treatment related non reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in of the dogs that resulted in a decrease in spermatogenesis in of the dogs at doses of 10 mg kg day Systemic exposure based on AUC at no observed adverse-effect level NOAEL 10 mg kg day for unbound tadalafil was similar to that expected in humans at the MRHD of 20 mg There were no treatment related testicular findings in rats or mice treated with doses up to 400 mg kg day for 2 years 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 fold greater than found in the plasma Following a single oral dose of 10 mg kg approximately 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 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 Adverse Reactions Tadalafil was administered to over 5700 men mean age 59 range 19 to 87 years during clinical trials worldwide Over 1000 patients were treated for 1 year or longer and over 1300 patients were treated for 6 months or more In placebo controlled Phase 3 clinical trials the discontinuation rate due to adverse events in patients treated with tadalafil 10 or 20 mg was compared to in placebo treated patients When tadalafil was taken as recommended in the placebo controlled clinical trials the following adverse events were