Skip to main content

Drug Interactions between atazanavir / cobicistat and sildenafil

This report displays the potential drug interactions for the following 2 drugs:

Edit list (add/remove drugs)

Interactions between your drugs

Major

sildenafil atazanavir

Applies to: sildenafil and atazanavir / cobicistat

CONTRAINDICATED: 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, administration of a single 100 mg dose of sildenafil during treatment with ritonavir (500 mg twice a day for 7 days) increased the mean sildenafil peak plasma concentration (Cmax) and systemic exposure (AUC) by 300% and 1000%, respectively, compared to administration 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: A safe and effective dosage of sildenafil has not been established for the treatment of pulmonary arterial hypertension when used in the presence of protease inhibitors. Due to the potential for increased sildenafil-associated adverse events including visual disturbances, hypotension, prolonged erection and syncope, this use is considered contraindicated. 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 doctor 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).

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  4. "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals PROD (2001):
  5. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  6. Barry M, Mulcahy F, Merry C, Gibbons S, Back D "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet 36 (1999): 289-304
  7. Nandwani R, Gourlay Y "Possible interaction between sildenafil and HIV combination therapy." Lancet 353 (1999): 840
  8. Hall MCS, Ahmad S "Interaction between sildenafil and HIV-1 combination therapy." Lancet 353 (1999): 2071-2
  9. Merry C, Barry MG, Ryan M, Tjia JF, Hennessy M, Eagling VA, Mulcahy F, Back DJ "Interaction of sildenafil and indinavir when co-administered to HIV-positive patients." AIDS 13 (1999): f101-7
  10. Warrington JS, Shader RI, vonMoltke LL, Greenblatt DJ "In vitro biotransformation of sildenafil (Viagra): Identification of human cytochromes and potential drug interactions." Drug Metab Disposition 28 (2000): 392-7
  11. Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, Buss N "Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir." Br J Clin Pharmacol 50 (2000): 99-107
  12. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  13. Hyland R, Roe GH, Jones BC, Smith DA "Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil." Br J Clin Pharmaacol 51 (2001): 239-48
  14. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  15. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  16. "Product Information. Revatio (sildenafil)." Pfizer U.S. Pharmaceuticals Group (2005):
  17. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
  18. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation (2011):
  19. "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals (2011):
View all 19 references

Switch to consumer interaction data

Major

sildenafil cobicistat

Applies to: sildenafil and atazanavir / cobicistat

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of sildenafil, which is primarily metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of sildenafil should be considered. In 14 healthy volunteers, administration of a single 100 mg dose of sildenafil in combination with the potent CYP450 3A4 inhibitor ritonavir (500 mg twice a day for 7 days) increased mean sildenafil peak plasma concentration (Cmax) and systemic exposure (AUC) 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 (SGC 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 protease inhibitor. 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. Another CYP450 3A4 inhibitor, erythromycin (500 mg twice daily for 5 days), increased single-dose sildenafil AUC by 182%.

MANAGEMENT: A safe and effective dosage of sildenafil has not been established for the treatment of pulmonary arterial hypertension when used in the presence of potent CYP450 3A4 inhibitors. Due to the potential for increased sildenafil-associated adverse events including visual disturbances, hypotension, prolonged erection and syncope, this use is considered contraindicated. When used for erectile dysfunction, 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 doctor 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).

References

  1. "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals PROD (2001):
  2. Nandwani R, Gourlay Y "Possible interaction between sildenafil and HIV combination therapy." Lancet 353 (1999): 840
  3. Hall MCS, Ahmad S "Interaction between sildenafil and HIV-1 combination therapy." Lancet 353 (1999): 2071-2
  4. Merry C, Barry MG, Ryan M, Tjia JF, Hennessy M, Eagling VA, Mulcahy F, Back DJ "Interaction of sildenafil and indinavir when co-administered to HIV-positive patients." AIDS 13 (1999): f101-7
  5. Warrington JS, Shader RI, vonMoltke LL, Greenblatt DJ "In vitro biotransformation of sildenafil (Viagra): Identification of human cytochromes and potential drug interactions." Drug Metab Disposition 28 (2000): 392-7
  6. Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, Buss N "Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir." Br J Clin Pharmacol 50 (2000): 99-107
  7. Hyland R, Roe GH, Jones BC, Smith DA "Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil." Br J Clin Pharmaacol 51 (2001): 239-48
  8. "Product Information. Revatio (sildenafil)." Pfizer U.S. Pharmaceuticals Group (2005):
  9. "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences (2012):
View all 9 references

Switch to consumer interaction data

Drug and food interactions

Moderate

sildenafil food

Applies to: sildenafil

GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.

MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.

References

  1. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther 71 (2002): 21-29

Switch to consumer interaction data

Moderate

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):

Switch to consumer interaction data

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

Report options

Loading...
QR code containing a link to this page

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer