Cialis Pharmacogenomics & Genetic Variability: How Your DNA Shapes Tadalafil Response

Does DNA change how tadalafil works?

Cialis is approved for erectile dysfunction (ED), for the signs and symptoms of benign prostatic hyperplasia (BPH), and for both together [1]. The label's dose adjustments turn on the indication, on kidney and liver function, and on other drugs the person takes [1]. It does not describe a genetic test or a genotype-based dose [1].

CYP3A4, the main metabolic pathway

Tadalafil is a substrate of and predominantly metabolized by CYP3A4, and its metabolites are not expected to be pharmacologically active [1]. The label measures that pathway with drugs rather than genes. Ketoconazole 400 mg daily raised tadalafil 20 mg exposure (AUC) by 312% and peak concentration by 22%; ketoconazole 200 mg daily raised tadalafil 10 mg AUC by 107% [1]. Ritonavir 200 mg twice daily raised tadalafil 20 mg AUC by 124% [1]. Rifampin 600 mg daily cut tadalafil 10 mg AUC by 88% [1]. With strong CYP3A4 inhibitors, the label caps Cialis at 10 mg every 72 hours for as-needed use, or 2.5 mg once daily [1].

Other factors that change exposure

In healthy men aged 65 or older, tadalafil exposure (AUC) was 25% higher than in younger men [1]. After single 5 to 10 mg doses, exposure was about doubled in people with mild (creatinine clearance 51 to 80 mL/min) or moderate (31 to 50 mL/min) renal impairment [1].

What response looked like in the main ED trials

In integrated analyses of five 12-week placebo-controlled trials, 1,112 men took placebo or tadalafil 2.5, 5, 10 or 20 mg as needed [2]. At 20 mg, erectile function on the International Index of Erectile Function improved by a mean 7.9 points, 75% of intercourse attempts were successful, and 81% reported improved erections versus 35% on placebo [2].