Warfarin with Lopinavir Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
Altered warfarin plasma concentrations
Interaction Summary
Concomitant use of lopinavir/ritonavir and warfarin may alter warfarin plasma concentrations and therefore, monitoring of INR is recommended in patients receiving concurrent lopinavir/ritonavir and warfarin. A case report described a 39-year-old male patient requiring higher doses of warfarin to maintain a therapeutic INR after receiving concurrent lopinavir/ritonavir therapy compared with a previous antiretroviral regimen that did not contain lopinavir/ritonavir . Another case report described decreased INR values with coadministration of lopinavir/ritonavir in a patient stabilized on warfarin .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant administration of lopinavir/ritonavir and warfarin may result in altered warfarin concentrations. Closely monitor the international normalized ratio (INR) in patients receiving concurrent lopinavir/ritonavir and warfarin therapy.
Mechanism Of Interaction
Altered warfarin metabolism
Literature Reports
A) A 39-year-old male patient required higher doses of warfarin to maintain a therapeutic INR after receiving concurrent lopinavir/ritonavir therapy compared with previous antiretroviral therapy (ART) that did not contain lopinavir/ritonavir. The patient was admitted to the hospital with a dyspnea and right leg swelling, and was found to have a pulmonary embolism and deep vein thrombosis. At this time, the patient was receiving ART with nevirapine 200 mg twice daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily for the treatment of HIV. He was not taking any other prescription drugs; however, he reported using marijuana daily. Anticoagulation therapy was initiated with enoxaparin 80 mg subQ twice daily and warfarin 5 mg daily, which produced an INR of 0.9. The warfarin dose was increased to 20 mg daily to maintain a therapeutic INR of 2 to 3. Eight months following the start of anticoagulation therapy, his antiviral regimen was changed to tenofovir 300 mg daily, didanosine enteric-coated 250 mg daily, and nelfinavir 1250 mg twice daily to maintain viral suppression. Following the start of the alternate antiretroviral regimen, warfarin 12.5 mg daily was sufficient to maintain his target INR. Eight months later, his antiviral regimen was changed again to didanosine enteric-coated 250 mg daily, emtricitabine 200 mg plus tenofovir 300 mg daily, and lopinavir 400 mg plus ritonavir 100 mg twice daily. His warfarin dose required adjustment to 17.5 mg daily after the start of the lopinavir/ritonavir-containing regimen .
B) A case report described decreased international normalized ratio (INR) values with the concomitant use of lopinavir/ritonavir in a 42-year-old male stabilized on warfarin. The patient, who had been treated with warfarin since receiving aortic valve replacement 12 years earlier, was hospitalized with chills and shortness of breath on exertion. His INR was maintained between 2 and 3 with a warfarin dose of 5.5 mg/day. During his hospital stay, he was initiated on co-trimoxazole for pneumonia, fluconazole and citalopram. The patient tested HIV positive and had a baseline CD4 cell count of 150 x 10(6)/L. Five days after discharge, his INR was 4.4. Subsequently, warfarin was withheld for 1 dose and reinitiated at alternating doses of 3 mg/day and 3.5 mg/day, and INR values were 3.8 and 2.1 at 3 days and 2 weeks, respectively. One month after discharge, antiretroviral therapy (zidovudine, lamivudine, and lopinavir/ritonavir) was initiated. Repeated testing rendered INR values between 1.1 and 1.3. Beginning at his 1-month follow-up visit, repeat testing was performed again over the next few weeks revealing INR values between 1 and 1.3. Patient non-adherence and changes in diet were ruled out as causes for decreased INR values. His warfarin dose was titrated to 11 mg/day over several months during which time his INR remained subtherapeutic. Following referral for anticoagulation management 1 month later, his INR stabilized between 2 and 3 with a warfarin dose of 13 mg/day. After receiving antiretroviral therapy for 7 months, his INR value was 2.6 and his CD4 cell count had risen to 330 x 10(6)/L with an HIV viral load less than 50 copies/mL. Induction of CYP2C9-mediated warfarin metabolism by lopinavir/ritonavir was suggested as a possible mechanism .
Warfarin Overview
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Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.