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.
Tadalafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by tadalafil enhances erectile function by increasing the amount of cGMP.
Nitrates - Administration of Tadalafil to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway.
Alpha Blockers - Administration of Tadalafil to patients taking any alpha-adrenergic antagonist other than 0.4 mg once-daily tamsulosin is contraindicated. In a drug-drug interaction study, when tadalafil 20 mg was administered to healthy subjects taking doxazosin (8 mg daily), there was a significant augmentation of the blood-pressure-lowering effect of doxazosin.
Hypersensitivity - Tadalafil is contraindicated for patients with a known hypersensitivity to tadalafil or any component of the tablet.