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Coumadin and MetroGel

Determining the interaction of Coumadin and MetroGel and the possibility of their joint administration.

Check result:

Coumadin <> MetroGel

Relevance: 01.06.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Using warfarin together with metroNIDAZOLE topical can cause you to bleed more easily. You may need a dose adjustment in addition to testing of your prothrombin time or International Normalized Ratio (INR). Call your doctor promptly if you have any unusual bleeding or bruising, vomiting, blood in your urine or stools, headache, dizziness, or weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR: Coadministration with vaginal metronidazole may enhance the hypoprothrombinemic effect of warfarin and other oral anticoagulants. The proposed mechanism is metronidazole inhibition of CYP450 2C9, the isoenzyme responsible for the metabolic clearance of the more active S(-) enantiomer of warfarin. The interaction has been reported with systemically administered metronidazole and warfarin. Significant bleeding and elevation of prothrombin time have been observed. No data are available for vaginally administered metronidazole. Although peak serum levels and systemic exposure are substantially lower than in systemic administration, the possibility of an interaction cannot be excluded.

MANAGEMENT: The potential for interaction with warfarin and other oral anticoagulants should be considered during coadministration with vaginal preparations of metronidazole. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation and discontinuation of metronidazole therapy in patients who are stabilized on their anticoagulant regimen. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References

Wells PS, Holbrook AM, Crowther NR, Hirsh J "Interactions of warfarin with drugs and food." Ann Intern Med 121 (1994): 676-83
Hermans JJ, Thijssen HH "Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics." Br J Pharmacol 110 (1993): 482-90
Kazmier FJ "A significant interaction between metronidazole and warfarin." Mayo Clin Proc 51 (1976): 782-4
Kelly JG, O'Malley K "Clinical pharmacokinetics of oral anticoagulants." Clin Pharmacokinet 4 (1979): 1-15
O'Reilly RA "The stereoselective interaction of warfarin and metronidazole in man." N Engl J Med 295 (1976): 354-7
Thijssen HH, Flinois JP, Beaune PH "Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes." Drug Metab Disposition 28 (2000): 1284-90
Miners JO, Birkett DJ "Cytochrome P4502C9: an enzyme of major importance in human drug metabolism." Br J Clin Pharmacol 45 (1998): 525-38
"Product Information. Metrogel-Vaginal (metronidazole)." Curatek Pharmaceuticals Ltd, Elk Grove Village, IL.
Dean RP, Talbert RL "Bleeding associated with concurrent warfarin and metronidazole therapy." Drug Intell Clin Pharm 14 (1980): 864-6
Laine K, Forsstrom J, Gronroos P, Irjala K, Kailajarvi M, Scheinin M "Frequency and clinical outcome of potentially harmful drug metabolic interactions in patients hospitalized on internal and pulmonary medicine wards: Focus on warfarin and cisapride." Ther Drug Monit 22 (2000): 503-9
Serlin MJ, Breckenridge AM "Drug interactions with warfarin." Drugs 25 (1983): 610-20
"Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.

Coumadin

Generic Name: warfarin

Brand name: Coumadin, Jantoven

Synonyms: n.a.

What is Coumadin?

MetroGel

Generic Name: metronidazole topical

Brand name: MetroCream, MetroGel, MetroGel Pump, MetroLotion, Noritate, Rosadan, MetroGel-Vaginal, Nuvessa, Vandazole

Synonyms: n.a.

What is MetroGel?

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In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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