Duloxetine with Warfarin Interaction Details

Brand Names Associated with Duloxetine

Brand Names Associated with Warfarin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

An increased risk of bleeding

Interaction Summary

Coadministration of DULoxetine and warfarin may result in altered anticoagulation effects including an increased risk of bleeding. The release of serotonin by platelets is involved in hemostasis. Bleeding events and increases in INR with concomitant therapy have been reported ; however, a study in healthy subjects (n=30) found no clinically significant changes in INR with concomitant administration of DULoxetine and warfarin at steady state conditions, or with dosage increase or duration of DULoxetine therapy . If coadministration is required, closely monitor anticoagulation effects during DULoxetine initiation and discontinuation .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of DULoxetine and warfarin may increase the risk of bleeding. If concomitant use is required, carefully monitor anticoagulation effects during DULoxetine initiation or discontinuation.

Mechanism Of Interaction

Additive effects on hemostasis

Literature Reports

A) No clinically significant changes in INR or bleeding time were observed with coadministration of DULoxetine and warfarin (at steady state conditions) compared with warfarin alone in healthy subjects (n=30; age range, 19 to 62 years). All subjects received warfarin 10 on day 1 then individualized dosing (range, 2 to 9 mg) daily on days 2 to 9 for a goal INR range of 1.5 to 2.0 for 3 consecutive days. After warfarin steady state was achieved, all subjects received DULoxetine 60 mg once daily for 4 days, then either continued 60 mg daily (n=15; group 1) or increased to 120 mg daily (n=15; group 2) for 10 days. Warfarin was discontinued on day 14. During concomitant administration among group 1 and 2, the mean INR changes from baseline ranged from -0.05 to +0.07 (90% confidence interval, -0.12 to +0.14). Additionally, mean INR changes from baseline were not significantly affected by dosage increase or by duration of DULoxetine therapy. Notably, a statistically significant prolongation in bleeding time was observed at day 14 in group 1 compared with warfarin alone; however, the difference was considered small (less than 2 minutes); whereas, no prolongation in bleeding time was observed in group 2. Additionally, the AUC (steady state) of warfarin R- and S-enantiomers was not affected with either dosage of DULoxetine. One subject discontinued due to mild epistaxis .

B) A population-based, case-controlled study of new coumarin users (acenocoumarol and phenprocoumon) with concomitant selective serotonin reuptake inhibitors (SSRIs) resulted in an increased risk of hospitalization due to non-gastrointestinal bleeding. Using national pharmacy and hospitalization records, Netherlands researchers identified 1848 cases that were admitted for abnormal bleeding and compared them with 5818 control subjects also taking coumarins. Median duration of treatment in patients was 220 days (range, 1 to 4690 days). Patients on SSRIs showed greater risk for hospitalization for nongastrointestinal bleeding (adjusted odds ratio (OR) 1.7, 95% confidence interval (CI), 1.1 to 2.5), however, the rate of gastrointestinal bleeding (adjusted OR 0.8, 95% CI, 0.4 to 1.5) was not significantly different .

C) A case report describes a 44-year-old female patient maintained on warfarin (INR 2.2) who developed petechiae/purpura (INR 5) after 55 days of concomitant DULoxetine treatment. Warfarin was initiated one year prior following ischemic stroke. Her daily, stable medication regimen included atorvastatin 10 mg, warfarin 7.5 mg to 10 mg, lamoTRIgine 50 mg, topiramate 200 mg, clonazePAM 2 mg, and albuterol extended-release 4 mg twice a day. DULoxetine 30 mg/day was added to treat depression-related insomnia. On day 58, only the warfarin was discontinued, and by day 85 the patient's INR exceeded 19. At this time, plasma warfarin level was 5.3 mcg/mL (17 mcmol/L; therapeutic range 2 to 8 mcg/mL (6 to 30 mcmol/L). Intravenous vitamin K 10 mg was administered, briefly decreasing the INR. By day 94, the INR was again elevated at 6.4, vitamin K-dependent clotting factors II, VII, and X were critically low, and fibrinogen level was normal. DULoxetine was then discontinued and 4 days later the INR measured 1.2, factor II increased to 48% and factor X increased to 54%. INR was 0.9 by day 105, and warfarin was restarted on day 110. By day 140, INR was stable at 2.2, with the patient again maintained on 7.5 to 10 mg/day. According to the Naranjo algorithm, the probability score for this adverse event was 12, or highly probable. The authors suggest that DULoxetine may have an effect on the CYP1A2 metabolism of warfarin, may have displaced warfarin from its protein-binding sites, or may have unique metabolic properties not yet determined .

Duloxetine Overview

• Duloxetine is used to treat depression in adults and generalized anxiety disorder (GAD; excessive worry and tension that disrupts daily life and lasts for 6 months or longer) in adults and children 7 years of age and older. Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes) in adults and fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep) in adults and children 13 years of age and older. It is also used to treat ongoing bone or muscle pain such as lower back pain or osteoarthritis (joint pain or stiffness that may worsen over time) in adults. Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance and stop the movement of pain signals in the brain.

Warfarin Overview

• 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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.