DRUGS THAT INTERACT WITH WARFARIN
Abciximab
Acetaminophen
Alcohol
(acute and chronic)
Allopurinol
Aminodarone
Aminoglutethimide
Amobarbital
Anabolic steroids
Aspirin
Azathioprine
Butabarbital
Butalbital
Carbamazepine
Cefoperazone
Cefotetan
Cefoxitin
Ceftriaxone
Chenodiol
Chloral hydrate
Chloramphenicol
Chlorpropamide
Chlorthalidone
Cholestyramine
Cimetidine
Ciprofloxacin
Clarithromycin
Clofibrate
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
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
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
Secobarbital
Sertaline
Simvastatin
Spironolactone
Stanozolol
Streptokinase
Sucralfate
Sulfamethizole
Sulfamethoxazole
Sulfinpyrazone
Sulfinpyrazone
Sulfisoxazole
Sulindac
Tamoxifen
Tetracycline
Thyroid hormone
Ticacillin
Ticlopidine
t-PA
Tolbutamide
Trazodone
Trimethoprimsulfamethoxazole
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 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)