Warfarin with Danazol Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Danazol
- Danazol
- Danocrine®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
A number of case reports have demonstrated that coadministration of oral anticoagulants and 17-alkylated androgens (fluoxymesterone, oxandrolone, oxymetholone, methyltestosterone, methandrostenolone, stanozolol) has resulted in prolonged prothrombin time and hemorrhages. Three case reports of danazol potentiating the effects of warfarin, including bleeding complications, have been reported .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
This combination should be avoided if possible. If cotherapy is used, the prothrombin time ratio or international normalized ratio (INR) should be closely monitored with the addition and withdrawal of treatment with danazol, and should be reassessed periodically during concurrent therapy. Adjustments of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation.
Mechanism Of Interaction
Inhibition of warfarin metabolism and/or direct effect of danazol on coagulation and fibrinolytic systems
Literature Reports
A) Anabolic steroids have been well documented to cause important interactions with dicumarol. The anabolic steroids enhance dicumarol's anticoagulant activity perhaps through reductions in clotting factor formation and increased clotting factor degradation. The 17-alpha-alkylated steroids (fluoxymesterone, oxandrolone, oxymetholone, methyltestosterone, methandrostenolone, stanozolol) appear to be more likely to induce this reaction than the non-substituted steroids .
B) Increased prothrombin time and hematemesis were observed in a 40-year-old female receiving warfarin for a prosthetic mitral valve and danazol for endometriosis. The patient had been receiving long-term anticoagulation therapy with warfarin 6 mg daily. Her prothrombin ratio was 2.3. Three weeks before admission the patient was started on danazol 200 mg twice daily for endometriosis. On admission her prothrombin ratio was 14. The patient presented with a history of hematemesis and easy bruising secondary to a loss of anticoagulant control. Five years earlier the patient had also been concomitantly treated with danazol and warfarin and experienced a prothrombin ratio of 18. Anticoagulant control returned to normal following withdrawal of danazol therapy. Lack of anticoagulant control was therefore attributed to the combination of danazol and warfarin therapy. A definite causal relationship between an increased prothrombin time with concomitant danazol and warfarin therapy in this patient was not established .
C) Two cases in which danazol potentiated the effect of warfarin, causing bleeding complications were reported. In the first case, a 47-year old woman had been taking alternating daily 5 mg and 4 mg warfarin doses. One month after danazol 200 mg twice daily had been added to her regimen for menorrhagia, she presented to the emergency room with gross hematuria. Her prothrombin time (PT) was measured to be 48.2 seconds, and two days later was 55.7 seconds. Both medications were discontinued. The patient was later rechallenged with danazol and required decreased warfarin doses (between 1.25 mg and 2.5 mg daily) to maintain a therapeutic PT .
D) A 28-year old woman had been taking warfarin 10 mg daily for protein C deficiency. Three weeks after starting danazol therapy at 600 mg daily, the patient presented to the emergency room with right knee pain and swelling and abdominal pain. Her prothrombin time was 38.6 seconds. The patient developed a large hemarthrosis of the right knee, a moderate hemorrhage of the right ovary and a small left psoas muscle hematoma. Warfarin was discontinued and after three days, the prothrombin time was again within the therapeutic range .
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.
Danazol Overview
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Danazol is used to treat endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body and causes infertility, pain before and during menstrual periods, pain during and after sexual activity, and heavy or irregular bleeding)..Danazol is also used to treat fibrocystic breast disease (swollen, tender breasts with noncancerous lumps) when other treatments are not successful. Danazol is also used to prevent attacks in people with hereditary angioedema (inherited condition that causes episodes of swelling in the hands, feet, face, airway, or intestines). Danazol is in a class of medications called androgenic hormones. It works to treat endometriosis by shrinking the displaced tissue of the uterus. It works to treat fibrocystic breast disease by blocking the release of hormones that cause the breast pain and lumps. It works to treat hereditary angioedema by increasing the amount of a natural substance in the body.
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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.