What If…Patient Wants to Use Viagra?
Sildenafil:
- substrate of CYP3A4
- potential for lopinavir/r to ? sildenafil concentrations
- dose-related side effects (H/A, vasodilation, etc.)
Start with lower sildenafil dose (i.e., 25 mg every 48 hours, titrate accordingly)
Notes:
- Sildenafil is the first oral phosphodiesterase inhibitor approved for the treatment of erectile dysfunction. Kinetics:
- substrate of CYP3A4; minor route of metabolism: CYP2C9
- weak inhibitor of CYP1A2, 2C9, 2C19, 2D6, 2E1, 3A4; unlikely to alter clearance of other drugs metabolized via these pathways
- Usual dose is 25-100 mg/day (for most patients, the recommended dose is 50 mg, taken 1 hour (range 0.5 - 4 hours) before sexual activity. Side effects (dose-related): headaches, vasodilation, dyspepsia, visual disturbances
- Drug interactions studied with the following protease inhibitors:
- indinavir: 4.4 fold ? sildenafil concentrations (i.e., plasma levels greater than that achieved with 100 mg sildenafil dosed alone); effects of sildenafil persisted up to 72 hours post-ingestion in some subjects.
- saquinavir: 140% increase in Cmax and a 210% increase in sildenafil AUC; no effect on saquinavir pharmacokinetics.
- ritonavir: 300% (4-fold) increase in sildenafil Cmax and a 1,000% (11-fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still ~200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone
- also potential for interactions with other protease inhibitors
Therefore, may wish to suggest a lower dose (I.e., 25 mg every 24-48 hours) and adjust according to efficacy/toxicity