DRUGS THAT INTERACT WITH WARFARINAbciximab

AcetaminophenAlcohol

(acute and chronic)Allopurinol

AminodaroneAminoglutethimide

AmobarbitalAnabolic steroids

AspirinAzathioprineButabarbital

ButalbitalCarbamazepineCefoperazone

CefotetanCefoxitin

CeftriaxoneChenodiol

Chloral hydrateChloramphenicolChlorpropamideChlorthalidoneCholestyramine

CimetidineCiprofloxacin

ClarithromycinClofibrate

Corticotropin

Cortisone

Coumadin

Cyclophosphamide

Danazol

Dextran

Dextrothyroxine

Diazoxide

Diclofenac

Dicloxaxillin

Diflunsial

Disulfram

Doxycycline

Erythromycin

Ethacrynic acid

Ethchlorvynol

Fenoprofen

Fluconazole

Fluorouracil

Gemfibrozil

Glucagon

Glutethimide

Griseofulvin

Haloperidol

Halothane

Heparin

Ofloxacin

Olsalazine

Omeprazole

Oxaprozin

Oxymetholone

Paraldehyde

Paroxetine

Penicillin G

Pentobarbital

Pentoxifylline

Phenobarbital

Phenylbutazone

Phenytoin

Piperacillin

Piroxicam

Prednisone

Primidone

Propafenone

Propoxyphene

Propranolol

Propylthiouracil

Phytonadione

Quinidine

Quinine

Ranitidine

Rifampin

Ibuprofen

Ifosamide

Indomethacin

Influenza virus vaccine

Itraconazole

Ketoprofen

Ketorolac

Levamisol

Levothyroxine

Liothyronine

Lovastatin

Mefenamic

Meprobamate

Methimazole

Methyldopa

Methylphenidate

Methylsalicylate

Miconzale

Metronidazole

Miconazole

Moricizine HCl

Nafcillin

Nalidixic acid

Naproxen

Neomycin

Norfloxacin

Secobarbital

Sertaline

Simvastatin

Spironolactone

Stanozolol

Streptokinase

Sucralfate

Sulfamethizole

Sulfamethoxazole

Sulfinpyrazone

Sulfinpyrazone

Sulfisoxazole

Sulindac

Tamoxifen

Tetracycline

Thyroid hormone

Ticacillin

Ticlopidine

t-PA

Tolbutamide

Trazodone

Trimethoprim-sulfamethoxazole

Urokinase

Valproate

Vitamin C

Vitamin E

Drug X S-warfarin

Agents that DECREASE metabolism (inhibit or compete for cytochrome P450)

are more important than those that increase metabolism

Drug X R-warfarin andS-warfarin

Must also consider that both forms ofwarfarin can interact with other drugs

DRUG INTERACTIONSDrug X S-warfarin

DRUG INTERACTIONS

PHARMACOKINETIC• ABSORPTION

binding in intestine

• DISTRIBUTION plasma protein binding

• ELIMINATIONcytP450 inhibition

cytP450 induction

Drug X S-warfarin

DRUG INTERACTIONS

PHARMACODYNAMIC• SYNERGISM

platelet/clotting factor function

• ANTAGONISM concentration of clotting

factors

• ALTERED VITAMIN K availability of vitamin K

Drug X S-warfarin

Both inhibitors and substrates of a particular CYP isozyme decrease the metabolism of substrates of that isozyme increased efficacy

Inducers increase the metabolism of substrates decreased efficacy

For example, for CYP 2C9, both amiodarone and carvedilol will increase the efficacy of celecoxib, but barbiturates will reduce it

In other words, drugs in the inhibitor and inducer columns can affect drugs in the substrate column, but substrates don’t affect inhibitors and inducers

Substrates can affect other substrates

Taking up the case of warfarin, the active enantiomer is S-warfarin which is metabolized by CYP 2C9.

That means we have to be most concerned by drugs that inhibit CYP 2C9 ---- i.e., amiodarone, cimetidine, etc., and especially fluvoxamine.

Drug X S-warfarin

Drug X R&S-warfarin

We also have to worry about drug interactions where warfarin causes an adverse drug interaction with another drug.

Neither warfarin enantiomer is an inducer or an inhibitor of CYP enzymes. So the drugs that could interact are ones that are substrates for the CYP isozymes that EITHER R- or S-warfarin is a substrate of. So you could expect interactions with amitriptyline, carvedilol, amitriptyline and alfentanil (reading just the first drug in the substrate list for each affected isozyme)