Ketoconazole markedly raises the levels of
tadalafil and very markedly raises the levels of vardenafil. There is some evidence that
ketoconazole also reduces sildenafil clearance. Itraconazole is predicted to interact similarly. Other azole antifungals that are potent inhibitors of CYP3A4 such as
posaconazole and
voriconazole would also be expected to interact similarly.
The manufacturers of sildenafil recommend that a starting dose of 25 mg of sildenafil should be used for treating erectile dysfunction. The manufacturers say that the use of sildenafil for
pulmonary hypertension is contraindicated (UK) or not recommended (US) with
ketoconazole or
itraconazole. If
itraconazole or
ketoconazole is given with
tadalafil, decrease the dose of
tadalafil if adverse effects become troublesome. The US manufacturer advises that the dose of
tadalafil should not exceed 10 mg in a 72-hour period, or 2.5 mg daily for patients taking
ketoconazole (and therefore probably itraconazole). The UK manufacturer of vardenafil advises avoiding the concurrent use of
ketoconazole in all patients, but specifically contraindicates concurrent use in those over 75-years-old. In contrast, the US manufacturer recommends that the dose of vardenafil should not exceed 5 mg in 24 hours when used with
itraconazole or
ketoconazole 200 mg daily, or 2.5 mg in 24 hours with
itraconazole or
ketoconazole 400 mg daily.