Fluvastatin Warfarin

Fluvastatin may increase warfarin toxicity because both compete with P450 2C9 for metabolism. Cerivastatin can cause fatal rhabdomyolysis risk with other statins unclear. 

Absorption of certain drugs, including those with neutral or cationic charge as well as anions, may be impaired by the resins. These include digitalis glycosides, thiazides, warfarin, tetracycline, thyroxine, iron salts, pravastatin, fluvastatin, folic acid, phenylbutazone, aspirin, and ascorbic acid. Any additional medication (except niacin) should be given 1 hour before or at least 2 hours after the resin to ensure adequate absorption. Colesevelam does not bind digoxin, warfarin, or reductase inhibitors. 

Interactions of statins with warfarin, resulting in an increased bleeding tendency, have been reported (51), including interactions of anticoagulants with both lovastatin (51) and fluvastatin (89). 

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased INR without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient s goal INR (91). 

Trilli LE, Kelley CL, Aspinall SL, Kroner BA. Potential interaction between warfarin and fluvastatin. Ann Pharmacother 1996 30(12) 1399-402. 

Kline SS, Harrell CC. Potential warfarin-fluvastatin interaction. Ann Pharmacother 1997 31(6) 790. 

STATINS ANTICOAGULANTS-ORAL Possible t anticoagulant effect with fluvastatin and simvastatin Uncertain possibly due to inhibition of CYP2C9-mediated metabolism of warfarin Monitor INR closely... 

Clinically important, potentially hazardous interactions with astemizole, atorvastatin, cyclosporine, fluvastatin, lovastatin, pimozide, pravastatin, rifabutin, simvastatin, warfarin... 

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

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...

Examples of therapeutic compounds metabolized by CYP2C9 include nonsteroidal antiinflammatory (NSAID) medications, irbesartan, naproxen, and fluvastatin (see Table 43-3). Proposed dose adjustments based on phenotype have been published for CYP2C9 drug substrates such as warfarin, glipizide, tolbutamide, and phenytoin. ... 

Cimetidine, fluconazole, fluvastatin, isoniazid, lovastatin, pravastatin, simvastatin, sulfaphenazole, tienilic acid, tolbutamide, warfarin... 

CYP2C9 20 10 Celecoxib Diclofenac Fluoxetine Fluvastatin Ibuprofen Irbesarten Naproxen Amitriptyline Phenytoin Tolbutamide Torsemide S-warfarin Rosiglitazone Amiodarone Fluconazole Fluvoxamine Fluvastatin Isoniazid Sertraline Sulfaphenazole Trimethoprin Zafirlukast Rifampin Clotrimazole Carbamazepine Hyperforin Phenobarbital Ritonavir... 

C. Toxicity Adverse effects include bloating, constipation, and an unpleasant gritty taste. Absorption of vitamins (eg, vitamin K, dietary folates) and drugs (.eg, digitalis, thiazides, warfarin, pravastatin, fluvastatin) may be impaired by the resins. 

Kim MJ, Nafzinger AN, Kashuba AD, Kirchheiner J, Bauer S, Gaedigk A, Bertino JS. Effects of fluvastatin and cigarette smoking on CYP2C9 activity measured using the probe S-warfarin. Eur J Clin Pharmacol 62, 431-6. 

Studies have suggested that fluvastatin and rosuvastatin can increase warfarin levels and/or effects. Other studies with atorvas-tatin, lovastatin, pravastatin, and simvastatin suggest that they do not usually significantly alter the effects of warfarin, although cases of bleeding have been seen when these statins were given with coumarins and fluindione. 

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