Interactions between viagra(sildenafil) and Fortovase (saquinavir)
saquinavir and sildenafil (Major Drug-Drug)
ADJUST DOSE: Coadministration with protease inhibitors (PIs), especially ritonavir, may significantly increase the plasma concentrations of sildenafil. The mechanism is PI inhibition of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sildenafil. In 14 healthy volunteers, ritonavir (500 mg twice a day for 7 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of sildenafil (100 mg single dose) by 300% and 1000%, respectively, compared to sildenafil given alone. At 24 hours, sildenafil plasma levels were still approximately 200 ng/mL as opposed to about 5 ng/mL with sildenafil alone. In a parallel study, saquinavir (soft gelatin capsule 1200 mg three times a day for 7 days) increased single-dose sildenafil Cmax and AUC by 140% and 210%, respectively, in 14 healthy volunteers. No change in safety or tolerability of sildenafil was observed with either PI. In six HIV-infected patients stabilized on triple antiretroviral therapy containing indinavir (800 mg three times a day), the AUC of a single 25 mg dose of sildenafil was 4.4 times higher than dose-normalized data from historical controls. The patients experienced headache, flushing, dyspepsia and rhinitis, and there was a mean maximal decrease in blood pressure of 14/10 mmHg. The interaction was also suspected in the death of a 47-year-old man who used sildenafil (25 mg) during treatment with ritonavir and saquinavir.
MANAGEMENT: Sildenafil should be administered with caution in patients receiving PI therapy. When used for erectile dysfunction, a lower starting dose of 25 mg should be considered for patients treated with saquinavir. For patients receiving other PIs, the maximum dosage of sildenafil should not exceed a single dose of 25 mg in any given 48-hour period. Patients should be advised to promptly notify their physician if they experience pain or tightness in the chest or jaw, irregular heartbeat, nausea, shortness of breath, visual disturbances, syncope, or prolonged erection (greater than 4 hours). Concomitant use with ritonavir is not recommended when sildenafil is prescribed for the treatment of pulmonary arterial hypertension.
