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Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate and Sildenafil

Determining the interaction of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate and Sildenafil and the possibility of their joint administration.

Check result:
Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate <> Sildenafil
Relevance: 07.07.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Talk to your doctor before using sildenafil together with cobicistat. Combining these medications may significantly increase the blood levels and effects of sildenafil. Depending on your condition, you may not be able to use these medications together, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience nausea, shortness of breath, dizziness, lightheadedness, fainting, visual disturbances, ringing in the ears, vision or hearing loss, chest pain or tightness, irregular heartbeat, and/or priapism (prolonged and painful erection unrelated to sexual activity), as these may be signs and symptoms of excessive sildenafil levels. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

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
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  • 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
  • "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences, Foster City, CA.
  • Nandwani R, Gourlay Y "Possible interaction between sildenafil and HIV combination therapy." Lancet 353 (1999): 840
  • 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
  • "Product Information. Viagra (sildenafil)." Pfizer US Pharmaceuticals, New York, NY.
  • 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
  • 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
  • "Product Information. Revatio (sildenafil)." Pfizer U.S. Pharmaceuticals Group, New York, NY.
Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate

Generic Name: cobicistat / elvitegravir / emtricitabine / tenofovir

Brand name: Genvoya, Stribild

Synonyms: Cobicistat, elvitegravir, emtricitabine, and tenofovir

Sildenafil

Generic Name: sildenafil

Brand name: Revatio, Viagra

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.