In the primary efficacy studies of general populations, 81 % of patients reported that tadalafil improved their erections as compared to 35 % with placebo. In clinical trials with tadalafil taken on demand for the treatment of erectile dysfunction, diarrhoea was reported more frequently in patients over 65 years of age. In another clinical pharmacology study, tadalafil (20 mg) was studied in combination with up to 4 classes of antihypertensives. In the primary efficacy studies, 75 % of intercourse attempts were successful in tadalafil treated patients as compared to 32 % with placebo.In a 12-week study performed in 186 patients (142 tadalafil, 44 placebo) with erectile dysfunction secondary to spinal cord injury, tadalafil significantly improved the erectile function leading to a mean per-subject proportion of successful attempts in patients treated with tadalafil 10 or 20 mg (flexible-dose, on demand) of 48 % as compared to 17 % with placebo.A single study has been performed in paediatric patients with Duchenne Muscular Dystrophy (DMD) in which no evidence of efficacy was seen. Consequently, it is not expected to be clinically active at observed metabolite concentrations.The mean oral clearance for tadalafil is 2.5 L/h and the mean half-life is 17.5 hours in healthy subjects. It allows continued monitoring of the benefit/risk balance of the medicinal product. The time of dosing (morning versus evening) had no clinically relevant effects on the rate and extent of absorption.The mean volume of distribution is approximately 63 L, indicating that tadalafil is distributed into tissues. Steady-state plasma concentrations are attained within 5 days of once-daily dosing.Pharmacokinetics determined with a population approach in patients with erectile dysfunction are similar to pharmacokinetics in subjects without erectile dysfunction.Healthy elderly subjects (65 years or over), had a lower oral clearance of tadalafil, resulting in 25 % higher exposure (AUC) relative to healthy subjects aged 19 to 45 years. This finding is consistent with the low affinity of tadalafil for PDE6 compared to PDE5. Tadalafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1), and as such potentiates the hypotensive effect of nitrates (see section 4.3).The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following an appropriate medical assessment. With regard to those interaction studies where only the 10 mg tadalafil dose was used, clinically relevant interactions at higher doses cannot be completely ruled out.Tadalafil is principally metabolised by CYP3A4.
Alcohol was administered in a manner to maximise the rate of alcohol absorption (overnight fast with no food until 2 hours after alcohol). A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and CThe role of transporters (for example p-glycoprotein) in the disposition of tadalafil is not known. Continue typing to refine. When suggestions are available use up and down arrows to review and ENTER to select. This results in smooth muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. A selective inhibitor of CYP3A4, ketoconazole (200 mg daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and CConsequently, the incidence of the adverse reactions listed in section 4.8 might be increased.The role of transporters (for example, p-glycoprotein) in the disposition of tadalafil is not known.
Treatments should be initiated at minimal dosage and progressively adjusted.In clinical pharmacology studies, the potential for tadalafil to augment the hypotensive effects of antihypertensive medicinal products was examined. As this may be relevant for all patients exposed to tadalafil, the patient should be advised that in case of sudden visual defect, he should stop taking Tadalafil and consult a physician immediately (see section 4.3).