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Jantoven and Modafinil

Determining the interaction of Jantoven and Modafinil and the possibility of their joint administration.

Check result:
Jantoven <> Modafinil
Relevance: 22.11.2022 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 modafinil 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: Theoretically, coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may increase the plasma concentrations of warfarin and other coumarin anticoagulants. Exposure of human hepatocytes to modafinil in vitro has produced concentration-dependent suppression of CYP450 2C9, the isoenzyme that metabolizes warfarin, but no indication of CYP450 2C9 suppression has been observed clinically. In a study in which 28 healthy subjects received warfarin (5 mg single dose) alone and after treatment with either modafinil (200 mg for 7 days followed by 400 mg for 21 days) or placebo, the pharmacokinetics of warfarin were not significantly altered following modafinil compared to placebo. However, the potential for more subtle interactions after chronic warfarin administration cannot be ruled out.

MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to anticoagulant metabolism, patients should be closely monitored during concomitant therapy with modafinil or armodafinil. The INR should be checked regularly for the first several months of coadministration and thereafter whenever modafinil or armodafinil dosing is changed or stopped. Patients should be advised to promptly report any signs of bleeding to their doctor, 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
  • Robertson P Jr, Hellriegel ET, Arora S, Nelson M "Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers." J Clin Pharmacol 42 (2002): 205-14
  • Robertson P, Decory HH, Madan A, Parkinson A "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos 28 (2000): 664-71
  • Thijssen HH, Flin ois JP, Beaune PH "Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes." Drug Metab Dispos 28 (2000): 1284-90
  • "Product Information. Nuvigil (armodafinil)." Cephalon Inc, West Chester, PA.
  • "Product Information. Provigil (modafinil)." Cephalon, Inc, West Chester, PA.
  • Cerner Multum, Inc. "Australian Product Information." O 0
Jantoven

Generic Name: warfarin

Brand name: Coumadin, Jantoven

Synonyms: n.a.

Modafinil

Generic Name: modafinil

Brand name: Provigil

Synonyms: n.a.

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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