No pharmaceutical opinion available for this interaction.
Lopinavir / ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Sildenafil (Revatio).
3A4 (major), 13 identified metabolites, 5 of these metabolites are linked to the metabolism of ritonavir, transporters: MRP1, MRP2, OATP1A2, OATP1B1, P-gp
2C19 (strong), 1A2, 2C9 (moderate) UGT (moderate)
3A4 and 2D6 (strong), transporters: BCRP, MRP2, OATP1A2, OATP1B1, OATP1B3, OATP2B1, P-gp
3A4 (active metabolite with about 20% of sildenafil activity) >> 2C9
1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (weak)
Possible increase of adverse effects.
Product monograph contraindicate to administer sildenafil at high dose with a potent CYP3A4 inhibitor. If it must be used, consider a dose reduction. By cons, no dose adjustment is currently available.
Monitor closely clinical efficacy and appearance of adverse effects.
Give extra caution to patients with hepatic or renal insufficiency, or older than 65 years.
Tadalafil (Adcirca) with dosage adjustments. See tadalafil (Adcirca).
Sildenafil toxicity: hypotension, tachycardia, headache, dizziness, flushing, visual changes (difficulty distinguishing blue and green) and syncope.
Ref #2375 : The sildenafil monograph reports that cimetidine (800 mg), a nonspecific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers. When a single 100 mg dose of sildenafil was co-administered with erythromycin, a CYP3A4 inhibitor, at steady state (500 mg BID for 5 days), there was a 182% increase in sildenafil AUC. The monograph suggests reducing the dose of Revatio to 20 mg daily when administered with weak or moderate CYP3A4 inhibitors.
Co-administration of sildenafil (100 mg ) in single dose with saquinavir, a CYP3A4 inhibitor, at steady state (1200 mg TID) resulted in a 140% increase in sildenafil Cmax and a 210% (3.1-fold) increase in sildenafil AUC.
In another study in healthy volunteers, co-administration with the HIV protease inhibitor ritonavir at steady state (500 mg BID) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC.
At 24 hours, the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. The product monograph contraindicate use with potent CYP3A4 inhibitors.