DRUGS THAT INTERACT WITH WARFARIN

Abciximab Corticotropin Ibuprofen Ofloxacin Secobarbital

Acetaminophen Cortisone Ifosamide Olsalazine Sertaline
Coumadin Indomethacin Omeprazole Simvastatin
Alcohol
Cyclophosphamide Influenza virus vaccine Oxaprozin Spironolactone
(acute and chronic)
Danazol Itraconazole Oxymetholone Stanozolol
Allopurinol Dextran Ketoprofen Paraldehyde Streptokinase
Aminodarone Dextrothyroxine Ketorolac Paroxetine Sucralfate
Aminoglutethimide Diazoxide Levamisol Penicillin G Sulfamethizole
Amobarbital Diclofenac Levothyroxine Pentobarbital Sulfamethoxazole
Dicloxaxillin Liothyronine Pentoxifylline Sulfinpyrazone
Anabolic steroids
Diflunsial Lovastatin Phenobarbital Sulfinpyrazone
Aspirin Disulfram Mefenamic Phenylbutazone Sulfisoxazole
Azathioprine Doxycycline Meprobamate Phenytoin Sulindac
Butabarbital Erythromycin Methimazole Piperacillin Tamoxifen
Ethacrynic acid Methyldopa Piroxicam Tetracycline
Butalbital
Ethchlorvynol Methylphenidate Prednisone Thyroid hormone
Carbamazepine Fenoprofen Methylsalicylate Primidone Ticacillin
Cefoperazone Fluconazole Miconzale Propafenone Ticlopidine
Cefotetan Fluorouracil Metronidazole Propoxyphene t-PA
Cefoxitin Gemfibrozil Miconazole Propranolol Tolbutamide
Glucagon Moricizine HCl Propylthiouracil Trazodone
Ceftriaxone
Glutethimide Nafcillin Phytonadione Trimethoprim-sulfamethoxazole
Chenodiol Griseofulvin Nalidixic acid Quinidine Urokinase
Chloral hydrate Haloperidol Naproxen Quinine Valproate
Chloramphenicol Halothane Neomycin Ranitidine Vitamin C
Chlorpropamide Heparin Norfloxacin Rifampin Vitamin E

Chlorthalidone
Cholestyramine
Cimetidine
Ciprofloxacin
Clarithromycin
Clofibrate
 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 and
S-warfarin

Must also consider that both forms of

warfarin can interact with other drugs
DRUG INTERACTIONS
Drug X S-warfarin
DRUG INTERACTIONS
Drug X S-warfarin

PHARMACOKINETIC
• ABSORPTION
 binding in intestine
• DISTRIBUTION
 plasma protein binding
• ELIMINATION
cytP450 inhibition
cytP450 induction
DRUG INTERACTIONS
Drug X S-warfarin

PHARMACODYNAMIC
• SYNERGISM
 platelet/clotting factor
function
• ANTAGONISM
 concentration of clotting
factors
• ALTERED VITAMIN K
 availability of vitamin K
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.
We also have to worry about drug
interactions where warfarin causes
an adverse drug interaction with
another drug.

Drug X S-warfarin

Drug X R&S-warfarin
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)