Warfarin drug interactions

Many medicines and some foods interact with warfarin but in most cases, INR can guide management.

Use the 2 tables below to minimise your patient's risk of bleeding or thromboembolism.

Practice points

  • Review medicines (including prescription, over-the-counter (OTC) and complementary medicines) with the patient at each visit, including short courses such as antibiotics that may have started and stopped in between INR visits (see Resource links below).
  • Prescribe an alternative non-interacting medicine when possible.1
  • Perform an INR test within 48–72 hours of starting, stopping or changing a dose of a medicine that potentially interacts with warfarin. For short courses lasting < 7 days, warfarin dosage adjustment is not essential.2 For longer courses, continue to monitor the INR every 48–72 hours and wait 3 to 7 days after starting a new medicine, before adjusting the warfarin dose accordingly.2
  • Monitor patients closely for signs and symptoms of bleeding and thromboembolism - see Anticoagulant Safety Checklist.
  • Remind patients to check with their doctor, pharmacist or dentist before starting, stopping or changing doses of any medicines (including prescription, OTC or complementary medicines).
  • Ask the patient about dramatic changes to diet and health status as this may also alter the effect of warfarin. See patient information on Diet and Warfarin

Clinically significant medicine and food interactions

Table 1: Medicines and foods that have a high probability of interactions3

Effect on INR
Level of causationA = Level I (highly probable)
Potentiation
↑ INR and increase bleeding risk
Alcohol (if concomitant liver disease)B
Anabolic steroids
Amiodarone
Boldo-fenugreek
Cimetidine
Ciprofloxacin 
Citalopram
Cotrimoxazole
Diltiazem
Entacapone
Erythromycin
Fenofibrate

Fish oil
Fluconazole
Isoniazid (≥ 600 mg daily)
Mango (1–6 daily)
Metronidazole
Miconazole oral gel
Miconazole vaginal suppositories
Omeprazole
Piroxicam
Propranolol
Quilinggao
Sertraline
Voriconazole

Inhibition
↓ INR and increase thromboembolic risk
Avocado (large amounts ≥ 100 g daily)
Barbiturates (e.g. phenobarbitone)
Carbamazepine
Cholestyramine
Griseofulvin
High vitamin K containing foods/enteral feeds
Mercaptopurine
Mesalazine
Ribavirin
Rifampicin

 

Table 2: Medicines and foods that probably interact3

Effect on INR Level of causationA = Level II (probable)
Potentiation
↑ INR and increase bleeding risk
Amoxycillin/clavulanic acid
Aspirin
Azithromycin
Celecoxib
Clarithromycin
Danshen
Dextropropoxyphene
Disulfiram
Dong quai
Fluorouracil
Fluvoxamine
Fluvastatin
Gemcitabine
Grapefruit juice
Interferon
Itraconazole
Lycium barbarum (Goji berry)
Paclitaxel
Paracetamol (≥ 2 g/day)
Phenytoin
Quinidine
Ritonavir
Ropinirole
Simvastatin
Tamoxifen
Tolterodine
Tramadol
Inhibition
↓ INR and increase thromboembolic risk

Azathioprine
Bosentan
Chelation therapy
Dicloxacillin
Ginseng
Influenza vaccine

Multivitamin preparations containing vitamin K1
Raloxifene
Ritonavir
Soy milk
Sucralfate
Note: This is not an exhaustive list. Also refer to the Resources below.
A. Refer to original paper for details regarding level of causation criteria.
B. Alcohol should be restricted to no more than 1–2 standard drinks per day. Heavy alcohol consumption also contributes to poor adherence, falls, alcohol-induced gastritis and poor diet.

Warfarin has many interactions

Many medicines and some foods interact with warfarin via a number of mechanisms:

  • Interference with warfarin metabolism predominantly by CYP2C9 inhibitors or inducers4, e.g. amiodarone, cotrimoxazole, fluvoxamine and carbamazepine.
  • Interruption of the vitamin K cycle4, e.g. paracetamol.
  • Reduced synthesis of vitamin K by intestinal flora4, e.g. antibiotics (although interactions of this type are predictable, their intensity is variable3).
  • Interference with platelet function4, e.g. antiplatelets, e.g. aspirin or clopidogrel, selective-serotonin reuptake inhibitors, e.g. citalopram or sertraline, serotonin-noradrenaline reuptake inhibitors, e.g. venlafaxine and fish oils may increase the risk of bleeding (and may do so without elevating the INR).
  • Injury to the gastrointestinal mucosa4, e.g. aspirin or other NSAIDs may increase the risk of bleeding (and may do so without elevating the INR).
  • Altered synthesis of clotting factors1, e.g. large changes in vitamin-K containing food intake or multivitamins preparations containing vitamin K1 (phytomenadione), particularly in patients with poor vitamin K status.5

INR monitoring guides the effect of most drug interactions and dosage adjustment. However, be aware that bleeding can still occur through some mechanisms and without an elevated INR.

References
  1. Australian medicines handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2013.
  2. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol 2011;154:311–24. [full text]
  3. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005;165:1095–106. [full text]
  4. Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ 2007;177:369–71. [full text]
  5. Baxter K (ed). Stockley's drug interactions [online]. London: Pharmaceutical Press, 2012.