Dabigatran Etexilate with Flibanserin Interaction Details
Brand Names Associated with Dabigatran Etexilate
- Dabigatran
- Pradaxa®
Brand Names Associated with Flibanserin
- Addyi®
- Flibanserin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 08, 2024
Interaction Effect
Increased dabigatran exposure and increased risk of bleeding
Interaction Summary
Concomitant use of dabigatran and a P-gp inhibitor may increase dabigatran exposure and risk of bleeding. P-gp inhibition and renal impairment are the major risk factors for increased dabigatran exposure, therefore adjustments may be necessary. For treatment of, recurrence risk reduction of, or prophylaxis after hip replacement surgery of DVT or pulmonary embolism (PE), avoid coadministration if CrCl is less than 50 mL/min. For stroke and systemic embolism risk reduction in non-valvular atrial fibrillation, avoid coadministration in severe renal impairment (CrCl less than 30 mL/min); in moderate impairment (CrCl 30 to 50 mL/min), reduce dabigatran to 75 mg twice daily if concomitant use of dronedarone or systemic ketoconazole is necessary. With CrCl 50 mL/min or greater, separate the timing of administration by several hours if dabigatran is used with a P-gp inhibitor. Caution may be necessary with coadministration of dabigatran and moderate to strong P-gp inhibitors regardless of kidney function , and consider avoiding use of a P-gp inhibitor with dabigatran in elderly patients .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of dabigatran and a P-gp inhibitor may increase dabigatran exposure and risk of bleeding. P-gp inhibition and renal impairment are the major risk factors for increased dabigatran exposure, therefore adjustments may be necessary. For treatment of, recurrence risk reduction of, or prophylaxis after hip replacement surgery of DVT or pulmonary embolism (PE), avoid coadministration if CrCl is less than 50 mL/min. For stroke and systemic embolism risk reduction in non-valvular atrial fibrillation, avoid coadministration in severe renal impairment (CrCl less than 30 mL/min); in moderate impairment (CrCl 30 to 50 mL/min), reduce dabigatran to 75 mg twice daily if concomitant use of dronedarone or systemic ketoconazole is necessary. With CrCl 50 mL/min or greater, separate the timing of administration by several hours if dabigatran is used with a P-gp inhibitor. Caution may be necessary with coadministration of dabigatran and moderate to strong P-gp inhibitors regardless of kidney function , and consider avoiding use of a P-gp inhibitor with dabigatran in elderly patients .
Mechanism Of Interaction
Inhibition of P-gp-mediated efflux transport of dabigatran
Literature Reports
A) A 76-year-old woman taking dabigatran 150 mg twice daily for bilateral lower extremity DVTs and low-dose quinidine (10 mg twice daily) for an unknown indication was admitted from a nursing home with abdominal pain and rectal bleeding. On admission she was found to have anemia (Hb, 4.9 g/dL) and coagulopathy (thrombin time (TT) greater than 60 seconds), with acute kidney injury (SCr of 2 mg/dL; baseline 0.8 mg/dL), and an elevated BUN at 90 mg/dL. She was diagnosed with acute blood loss anemia secondary to lower GI bleeding likely related to dabigatran use. Bleeding risk associated with catheter placement precluded initiation of hemodialysis. Transfusion measures and treatment with idarucizumab initially normalized the patient's Hb (8.2 g/dL) and TT (14.3 seconds), but she experienced rebleeding, and the TT returned to greater than 60 seconds when rechecked approximately 20 hours after administration of idarucizumab. A 10-day hospitalization for persistent coagulopathy, rectal bleeding, and renal impairment was necessary, and the patient received 2 additional doses of idarucizumab on hospital days 2 and 4, with each treatment providing only temporary normalization of coagulation parameters. The patient continued to have rectal bleeding until day 5 at which point it began to improve, however TT remained elevated until hospital day 9. While renal impairment may have contributed to reduced dabigatran clearance in this case, quinidine (a P-gp inhibitor), was thought to have contributed to the initial suspected supratherapeutic levels of dabigatran .
B) In a comparative effectiveness study of patients with nonvalvular atrial fibrillation and normal kidney function, the overall bleeding rate was 52% higher (244.9 vs 158.4 per 1000 person-years; HR, 1.52; 95% CI, 1.05 to 2.2) with coadministration of dabigatran and verapamil or diltiazem (n=750) compared with coadministration with amlodipine (n=1316), and 43% higher (291.3 vs 199.7 per 1000 patient-years; HR, 1.43; 95% CI, 1.02 to 2) with dabigatran and verapamil or diltiazem (n=764) compared with metoprolol (n=1334). Additionally, overall gastrointestinal (GI) bleeding (HR, 2.16; 95% CI, 1.3 to 3.6), minor bleeding (HR, 1.56; 95% CI, 1.07 to 2.27) and GI minor bleeding (HR, 2.16; 95% CI, 1.29 to 3.63) were also significantly increased with dabigatran and verapamil or diltiazem compared with amlodipine, and overall GI bleeding (HR, 2.32; 95% CI, 1.42 to 3.79), major/moderate bleeding (HR, 3.32; 1.54 to 7.16), major/moderate GI bleeding (HR, 5.49; 95% CI, 1.67 to 18.03), and GI minor bleeding (HR, 2.33; 95% CI, 1.42 to 3.82) were significantly increased with dabigatran and verapamil or diltiazem compared with metoprolol. Patients received dabigatran 150 mg twice daily. Caution may be necessary with coadministration of dabigatran with verapamil and diltiazem, and possibly other moderate to strong P-gp inhibitors, regardless of kidney function .
C) Concomitant use of dabigatran and simvastatin (n=502) or lovastatin (n=27), both P-glycoprotein (P-gp) inhibitors, significantly increased the risk of major hemorrhage by 46% compared with other statins not implicated in P-gp inhibition (atorvastatin, pravastatin, fluvastatin or rosuvastatin) in a study of patients 66 years or older (median, 82 years) with major hemorrhage (n=1117 cases and 4465 controls). Simvastatin itself was associated with a significant 44% increased risk of major hemorrhage, while lovastatin itself had a nonsignificant 90% increased risk compared with other statins .
Dabigatran Etexilate Overview
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Dabigatran is used to treat deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in adults and children 3 months of age and older who have been treated with an injectable anticoagulant ('blood thinner'). It is also used to reduce the risk of a DVT and PE from happening again after initial treatment is completed in adults and children 3 months of age and older. Dabigatran is used to help prevent DVT and PE in adults who have had hip replacement surgery. Dabigatran is also used to help prevent strokes or serious blood clots in adults who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) without heart valve disease. Dabigatran is in a class of anticoagulant medications called direct thrombin inhibitors. It works by preventing blood clots from forming in the body.
Flibanserin Overview
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Flibanserin is used to treat women with hypoactive sexual desire disorder (HSDD; a low sexual desire that causes distress or interpersonal difficulty) who have not experienced menopause (change of life; the end of monthly menstrual periods). Flibanserin should not be used for the treatment of HSDD in women who have gone through menopause or in men or to improve sexual performance. Flibanserin is in a class of medications called a serotonin receptor 1A agonist/serotonin receptor 2A antagonist. It works by changing the activity of serotonin and other natural substances in the brain.
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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.