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Flagyl 375 and Warfarin

Determining the interaction of Flagyl 375 and Warfarin and the possibility of their joint administration.

Check result:

Flagyl 375 <> Warfarin

Relevance: 26.10.2023 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 may cause you to bleed more easily. You may need a dose adjustment based on 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 CLOSELY: Coadministration with metronidazole may increase the plasma concentrations and hypoprothrombinemic effect of warfarin. 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 was associated with significant bleeding and elevation of prothrombin time in two case reports. No data are available for other oral anticoagulants, although at least one other coumarin derivative is known to be metabolized by CYP450 2C9.

MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to warfarin metabolism, patients should be closely monitored during concomitant therapy with metronidazole. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation or discontinuation of metronidazole in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking. 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

Hermida J, Zarza J, Alberca I, et al. "Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol." Blood 99 (2002): 4237-9
Venkatakrishnan K, vonMoltke LL, Greenblatt DJ "Effects of the antifungal agents on oxidative drug metabolism - Clinical relevance." Clin Pharmacokinet 38 (2000): 111-80
"Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
Takahashi H, Wilkinson GR, Caraco Y, et al. "Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients." Clin Pharmacol Ther 73 (2003): 253-63
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
Dean RP, Talbert RL "Bleeding associated with concurrent warfarin and metronidazole therapy." Drug Intell Clin Pharm 14 (1980): 864-6
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
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
O'Reilly RA "The stereoselective interaction of warfarin and metronidazole in man." N Engl J Med 295 (1976): 354-7
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

Flagyl 375

Generic Name: metronidazole

Brand name: FIRST Metronidazole, Flagyl, Flagyl 375, MetroGel

Synonyms: Flagyl 375 Capsules

What is Flagyl 375?

Warfarin

Generic Name: warfarin

Brand name: Coumadin, Jantoven

Synonyms: n.a.

What is Warfarin?

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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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