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

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

Check result:
Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate <> Savaysa
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:

Cobicistat may increase the blood levels of edoxaban. This can increase the risk of serious or life-threatening bleeding complications. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness; lightheadedness; red or black, tarry stools; coughing up or vomiting fresh or dried blood that looks like coffee grounds; severe headache; and weakness. 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:

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) such as cobicistat may increase the plasma concentrations of edoxaban, which is a substrate of the efflux transporter. In a single-center, two-arm, single-sequence, open-label study, the AUC and Cmax of another P-gp substrate, dabigatran, both increased by 127% when administered simultaneously with cobicistat (p-value less than 0.001 for AUC and Cmax). In addition, thrombin time (TT) at 24 hours post-dose increased by 51% when dabigatran and cobicistat were given simultaneously compared to dabigatran alone (p-value less than 0.001).

MANAGEMENT: When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned. Other P-gp inhibitors were not permitted in the study, and patients on antiretroviral therapy (ritonavir, nelfinavir, indinavir, saquinavir) as well as cyclosporine were excluded from the study. Following discontinuation of the P-gp inhibitor, edoxaban dosage should be returned to the regular dosage of 60 mg once daily. No dosage adjustment is recommended for edoxaban when used in the treatment of nonvalvular atrial fibrillation.

References
  • "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb, Princeton, NJ.
  • "Product Information. Genvoya (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences, Foster City, CA.
  • Kumar P, Gordon LA, et. al "Differential influence of the antiretroviral pharmacokinetic enhancers ritonavir and cobicistat on intestinal p-glycoprotein transport and the pharmacokinetic/pharmacodynamics disposition of dabigatran. Available from: URL: https://www.ncbi.nlm.nih.gov/pm" Antimicrob Agents Chemother 61 (2017): 1-12
  • Mendell J, Zahir H, Matsushima N, et al. "Drug-Drug Interaction Studies of Cardiovascular Drugs Involving P-Glycoprotein, an Efflux Transporter, on the Pharmacokinetics of Edoxaban, an Oral Factor Xa Inhibitor." Am J Cardiovasc Drugs (2013):
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • "Product Information. Symtuza (cobicistat/darunavir/emtricitabine/tenof)." Janssen Pharmaceuticals, Titusville, NJ.
  • "Product Information. Tybost (cobicistat)." Gilead Sciences, Foster City, CA.
  • "Product Information. Savaysa (edoxaban)." Daiichi Sankyo, Inc., Parsippany, NJ.
  • "Product Information. Prezcobix (cobicistat-darunavir)." Janssen Pharmaceuticals, Titusville, NJ.
  • "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences, Foster City, CA.
  • Parasrampuria DA, Mendell J, Shi M, Matsushima N, Zahir H, Truitt K "Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine." Br J Clin Pharmacol 0 (2016): epub
Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate

Generic Name: cobicistat / elvitegravir / emtricitabine / tenofovir

Brand name: Genvoya, Stribild

Synonyms: Cobicistat, elvitegravir, emtricitabine, and tenofovir

Savaysa

Generic Name: edoxaban

Brand name: Savaysa

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.