Diclofenac Coumarins

Figure 17.4 Compounds which are mentioned throughtout the chapter and numbered in the main text as follows (1) DMZ, (2) diclofenac, (3) flurbiprofen, (4) warfarin, (5) fluconazole, (6) coumarin, (7) dapsone, (8) retinoic acid, (9) arachidonic acid, (10) troglitazone, (11) fluvastatin, (12) cerivastatin, (13) taxol, (14) gemfibrozil, (15) verapamil, (16) amodiaquine, (17) amiodarone, (18) metyrapone, (19) progesterone, (20) testosterone, (21) erythromycin, (22) ketoconazole, (23) nicotine, (24) IV -Nitrosonor-nicotine, (25) 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone...

A 39-ycar-old woman taking acenocoumarol, celiprolol, triamterene, cyclothiazide, pravastatin and diosmin had a rise in her prothrombin levels from 0.3 to 1 within 8 days of starting to take diclofenac and misoprostol 400 micrograms daily. A day after these two drugs had been withdrawn her prothrombin level had fallen to 0.67, and after another 3 days to 0.32. The reasons for this reaction are not known, but suspicion falls on the misoprostol beeause diclofenac, if and when it interacts with anticoagulants, increases rather than reduces their effects (see Coumarins -i- NSAIDs Diclofenac , p.429). But just why misoprostol should cause these changes is not clear. 

For studies, including the one assessing the effect of CYI 2C9 substrates, such as diclofenac, on the risk of bleeding when used with warfarin, see Coumarins and related drugs + NSAIDs , p.427. 

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