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Edoxaban Tosylate and Kaletra Oral Solution

Determining the interaction of Edoxaban Tosylate and Kaletra Oral Solution and the possibility of their joint administration.

Check result:
Edoxaban Tosylate <> Kaletra Oral Solution
Relevance: 11.12.2022 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:

Ritonavir 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 ritonavir may increase the plasma concentrations of edoxaban, which is a substrate of the efflux transporter. In healthy volunteers, single-dose edoxaban systemic exposure (AUC) increased approximately 80% to 90% by erythromycin, dronedarone, and ketoconazole; 70% to 80% by cyclosporine and quinidine; 50% by verapamil; and 40% by amiodarone. The peak plasma concentration (Cmax) of edoxaban also increased by approximately 45% to 90% with these drugs. In another study, dabigatran etexilate (150 mg), another P-gp substrate, and ritonavir (100 mg) were administered simultaneously and separately (2 hours apart). When administered together, thrombin time (TT) at 24 hours post-dose increased by 31% while no significant changes in dabigatran pharmacokinetic parameters were observed. When dabigatran was given 2 hours before ritonavir, dabigatran AUC decreased by 29% while no significant changes in TT were observed.

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. Technivie (ombitasvir/paritaprevir/ritonavir)." AbbVie US LLC, North Chicago, IL.
  • "Product Information. Symtuza (cobicistat/darunavir/emtricitabine/tenof)." Janssen Pharmaceuticals, Titusville, NJ.
  • 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
  • "Product Information. Savaysa (edoxaban)." Daiichi Sankyo, Inc., Parsippany, NJ.
  • "Product Information. Prezcobix (cobicistat-darunavir)." Janssen Pharmaceuticals, Titusville, NJ.
  • "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical, Abbott Park, IL.
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • "Product Information. Prezista (darunavir)." Ortho Biotech Inc, Bridgewater, NJ.
  • "Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
  • Cerner Multum, Inc. "Australian Product Information." O 0
  • Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
  • "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprevir/ritonavir)." AbbVie US LLC, North Chicago, IL.
Edoxaban Tosylate

Generic Name: edoxaban

Brand name: Savaysa

Synonyms: Edoxaban

Kaletra Oral Solution

Generic Name: lopinavir / ritonavir

Brand name: Kaletra

Synonyms: Kaletra

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.

Interaction with food and lifestyle