Indinavir and saquinavir can cause marked rises in
serum sildenafil levels;
ritonavir raises
tadalafil levels; and
ritonavir and indinavir raise vardenafil levels. It seems likely that all
protease inhibitors will interact with these phosphodiesterase inhibitors.
In general, it is recommended that a low sildenafil starting dose of 25 mg should be considered for erectile dysfunction, and 20 mg twice daily for
pulmonary hypertension in those taking
protease inhibitors (but see
ritonavir, above). For indinavir a starting dose of 12.5 mg may be more appropriate for erectile dysfunction, and the maximum dosage frequency should be reduced to once or twice weekly. The US manufacturer advises that the dose of
tadalafil should not exceed 10 mg every 72 hours in patients taking
ritonavir. Similar precautions would seem prudent with other
protease inhibitors. Due to the large rises in vardenafil levels, the UK manufacturer contraindicates its use with
protease inhibitors that are potent CYP3A4 inhibitors (they name
ritonavir and indinavir). In contrast, the US prescribing information recommends dose restrictions as follows: the dose of vardenafil should not exceed 2.5 mg in 24 hours when used with
atazanavir, indinavir, or saquinavir, and should not exceed 2.5 mg in 72 hours when used with
ritonavir. Similar precautions would seem prudent with other
protease inhibitors.