Warfarin with Cimetidine Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Cimetidine
- Cimetidine
- Tagamet®
- Tagamet® HB
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Cimetidine inhibits hepatic metabolism of warfarin (over one to two weeks) and may increase warfarin levels by 20 to 30%. Once cimetidine is discontinued, it takes approximately one week to return to pretreatment state. In a case series of 6 patients anticoagulated with warfarin, concomitant exposure to cimetidine extended the prothrombin time (PT) by a mean of 12.6 seconds . Famotidine, or nizatidine do not appear to interact with warfarin .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Use of cimetidine in patients requiring anticoagulation with warfarin should be avoided when possible. Alternative H2 antagonist agents such as famotidine or nizatidine are preferable in patients requiring antisecretory therapy. If cimetidine is used in combination with warfarin, frequent monitoring of the prothrombin time is necessary until any response on the anticoagulant effect is manifested and is stabilized at an acceptable level.
Mechanism Of Interaction
Decreased warfarin metabolism
Literature Reports
A) Administration of cimetidine or ranitidine concurrently with warfarin has been reported to enhance the hypoprothrombinemic response to warfarin. In one study, the combination of warfarin 10 mg and cimetidine 1000 mg daily for seven days or ranitidine 300 mg daily for seven days decreased warfarin clearance by 36 and 27%, respectively. The reduction in warfarin clearance was further inhibited by an increase in ranitidine dose to 700 mg daily for seven days . Concomitant warfarin and cimetidine 1 g daily resulted in a 20% increase in prothrombin time .
B) The addition of oral cimetidine 300 mg four times daily or 800 mg once daily at nighttime in patients receiving maintenance warfarin therapy with a prothrombin time (PT) of 1.2 to 2 times the laboratory standard did not result in significant enhancement of anticoagulant effects, although a decrease in warfarin clearance was observed. Although the PT ratio was increased, it remained within therapeutic recommendations. Since the PT ratio and warfarin serum concentrations were increased, it was suggested that the PT be monitored during combined therapy .
C) Concurrent cimetidine and racemic warfarin therapy resulted in no significant change in the pharmacodynamics of warfarin, and the pharmacokinetics of the more potent S-enantiomer were unchanged. A decrease in clearance of the less active R-enantiomer was observed, which may have been related to inhibition of hepatic 6-hydroxylation to cimetidine. This may explain how cimetidine increases warfarin levels in patients but does not always affect PT .
D) Various pharmacokinetic parameters have been altered during concomitant use of cimetidine and warfarin. The mean percentage increase in prothrombin time AUC (area under the curve) and plasma concentration AUC of warfarin were 20% and 26%, respectively, when 11 individuals were administered cimetidine 300 milligrams four times daily for 8 days and warfarin 1.5 milligrams/kilogram was added on the fourth day .
E) In one case report, a 19-year-old patient was stabilized on warfarin 6 mg/day with a prothrombin time between 18 and 26 seconds. Cimetidine 300 milligrams three times daily was prescribed to treat dyspepsia. A few days following the addition of cimetidine the patient presented with severe epigastric pain, a pulse of 156 beats/minute and the prothrombin time, hemoglobin, and partial thromboplastin time of 90 seconds, 9.8 g/dL, and 110 seconds, respectively. Following treatment, the patient improved and was discharged .
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.
Cimetidine Overview
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Cimetidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter cimetidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Cimetidine is in a class of medications called H2 blockers. It decreases the amount of acid made in the stomach.
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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.