
There were no treatment-related testicular
Carcinogenesis - Tadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold for mice, and 14- and 26-fold for male and female rats, respectively, the exposures in human males given Maximum Recommended Human Dose (MRHD) of 20 mg. Mutagenesis - Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. Impairment of Fertility - There were no effects on fertility, 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. 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. findings in rats or mice
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treated with doses up to
Across all clinical studies with tadalafil tablets, reports of changes in color vision were rare (<0.1% of patients). Three studies were conducted in men to assess the potential effect on sperm characteristics of tadalafil 10 mg (one 6 month study) and 20 mg (one 6 month and one 9 month study) administered daily. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 mg or 20 mg of tadalafil compared to placebo. The effect of a single 100-mg dose of tadalafil on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double-blinded, placebo, and active (intravenous ibutilide) -controlled crossover study in 90 healthy males aged 18 to 53 years. In this study, the mean increase in heart rate associated with a 100-mg dose of tadalafil compared to placebo was 3.1 beats per minute.
Over a dose range of 2.5 mg to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. Mean tadalafil concentrations measured after the administration of a single oral dose of 20 mg and single and once daily multiple doses of 5 mg, from a separate study, (see Figure 4) to healthy male subjects are depicted in Figure 4. Figure 4: Plasma tadalafil concentrations (mean ± SD) following a single 20-mg tadalafil dose and single and once daily multiple doses of 5 mg Absorption - After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined. The rate and extent of absorption of tadalafil are not influenced by food; thus tadalafil tablets may be taken with or without food.
Distribution - The mean apparent volume of distribution following oral administration is approximately 63 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of indian cialis tadalafil tadalafil in plasma is bound to proteins. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects. Metabolism - Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations. 400 mg/kg/day for 2 years.
| Ingredient | Amount per Dose | Purpose | Notes |
|---|---|---|---|
| Tadalafil | 20 mg | Active ingredient, vasodilator | Main component for ED |
| Microcrystalline Cellulose | - | Filler | Binds ingredients |
| Magnesium Stearate | - | Excipient | Improves pill stability |
| Titanium Dioxide | - | Coloring agent | Provides yellow color |
Animal studies showed vascular inflammation
in tadalafil-treated mice, rats, and dogs.