Drug Interactions

Increased risk of bleeding or thromboembolism

A number of clinically significant interactions are known to occur with warfarin and these may be reflected by increases or decreases in the international normalised ratio (INR). The tables below are not exhaustive, but provide a general guide.

It is important to increase the frequency of INR monitoring when any interacting medications are added OR stopped.

Drugs Expected to Increase the Anticoagulant Effect of Warfarin
Allopurinol  Gemfibrozil
Amiodarone  Heparin 
Aspirin  Isoniazid (600 mg/d)
Bezafibrate  Itraconazole
Cefotetan  Ketoconazole
Cefoxitin  Lanzoprazole 
Ceftriaxone  Metronidazole 
Cephazolin  Miconazole 
Cimetidine  Norfloxacin 
Ciprofloxacin  NSAIDs eg. diclofenac
Clarithromycin  Ofloxacin 
Cephamandole  Omeprazole 
Citalopram  Paracetamol (> 2g/day for > a week)
Cotrimoxazole  Paroxetine 
Cyclophosphamide  Phenytoin (transient increase)
Danazol  Quinidine 
Dextropropoxyphene  Sertraline 
Disulfiram  Simvastatin 
Doxycycline  Sodium Valproate
Erythromycin  Sulphamethoxazole
Fluconazole  Tamoxifen
Fluoxetine  Tetracycline
Flutamide  Trimethoprim
Fluvastatin  

 

 

Drugs which may decrease the anticoagulant effect of warfarin either by increasing its metabolism or indirectly by interfering with absorption:

Drugs which may Decrease the Anticoagulant Effect 
Alcohol (>3 alcoholic drinks/day)  Oral contraceptives & oestrogens
Antacids  Penicillin (high dose intravenous)
Azathioprine  Phenobarbitone
Carbamazepine  Phenytoin
Carbimazole  Primidone
Cholestyramine  Propylthiouracil
Colestipol  Rifampicin
Enteral feeds (some contain vitamin K)  Sucralfate
Griseofulvin Vitamin K

 

 

Drugs Which Affect Platelet Function
Aspirin  Dipyridamole
Clopidogrel  Ticlopidine





 

 

Complementary Medicines Which may Increase the Anticoagulant Effect
Danshen  Horse chestnut
Dong Quai  Papain/Papaya extract
Ginger  Vitamin E >400iu/day
Garlic  Fish oil








 

 

Complementary Medicines Which may Decrease the Anticoagulant Effect
Coenzyme Q10  Green Tea 
Ginseng  St John’s Wort





 

 

Complementary Medicines which Affect Platelet Function
Feverfew   Ginkgo biloba
Garlic  Fish oil
Ginger  Liquorice

 


The impact of such interactions may be delayed and only become apparent three to four days after initiation of the interacting drug. Similarly, reversal of the increased INR can take several days after the interacting drug is withdrawn.

Addition or withdrawal of any concurrent drug therefore needs to be accompanied by closer monitoring of the INR to evaluate the effect on warfarin, followed by appropriate dose adjustments, if required, to restore the INR to the target therapeutic range.