Drug Interactions between Atripla and Viagra

ADJUST DOSE: Coadministration with moderate to potent CYP450 3A4 inducers may significantly decrease the plasma concentrations and effects of sildenafil, which is primarily metabolized by CYP450 3A4 and, to a lesser extent, by CYP450 2C9. This interaction has been demonstrated in studies using bosentan, a moderate CYP450 3A4 inducer and weak CYP450 2C9 inducer in vivo as well as an in vitro inducer of CYP450 2C19. Coadministration of oral sildenafil (80 mg three times daily) at steady state with bosentan (125 mg twice daily) at steady state over 6 days in healthy adult volunteers decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of sildenafil by 62.6% and 55.4%, respectively. The same effect was also observed with lower doses of oral sildenafil (20 mg three times daily) added to bosentan therapy (62.5 mg - 125 mg twice daily). The labeling for some sildenafil formulations used for pulmonary arterial hypertension (PAH) reported a population pharmacokinetic analysis of data from patients in clinical trials which indicated an approximately 3-fold increase in sildenafil clearance when co-administered with mild CYP450 3A4 inducers. However, this increased clearance was not reflected in a population pharmacokinetic analysis described in the labeling of some sildenafil formulations indicated for erectile dysfunction. More potent CYP450 3A4 inducers are expected to have greater effects than those observed with bosentan or mild inducers; however, data are not available. Likewise, clinical data regarding this interaction in pediatric patients are also unavailable.

MANAGEMENT: In adult patients being treated for pulmonary arterial hypertension (PAH), the dose of sildenafil may need to be increased when initiating treatment with moderate to potent CYP450 3A4 inducers. Conversely, the manufacturer recommends reducing the dose of sildenafil to 20 mg orally three times daily when discontinuing treatment with moderate to potent CYP450 3A4 inducers. Patients being treated for erectile dysfunction should be monitored closely and may require a dose adjustment of sildenafil if a moderate or strong CYP450 3A4 inducer is initiated or discontinued. Dosing should be guided by the patient's symptoms, ability to tolerate sildenafil, and recommendations provided in the product labeling.

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MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

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MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

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