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Sr. Executive / Executive, Production; THE IBN SINA PHARMACEUTICAL IND LTD

 Warfarin Interaction The prevalent risk for patient
Update: 2011-05-02

Warfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice and is still popular for this purpose. A few years after its introduction, warfarin was found to be effective and relatively safe for preventing thrombosis and embolism (abnormal formation and migration of blood clots) in many disorders. It was approved for use as a medication in the early 1950s and has remained popular ever since; warfarin is the most widely prescribed anticoagulant drug. Despite its effectiveness, treatment with warfarin has several shortcomings. Many commonly used medications interact with warfarin, as do some foods, and its activity has to be monitored by frequent blood testing for the international normalized ratio (INR) to ensure an adequate yet safe dose is taken.

Warfarin is prescribed to people with an increased tendency for thrombosis or as secondary prophylaxis (prevention of further episodes) in those individuals that have already formed a blood clot (thrombus). Warfarin treatment can help prevent formation of future blood clots and help reduce the risk of embolism (migration of a thrombus to a spot where it blocks blood supply to a vital organ). Common clinical indications for warfarin use are atrial fibrillation, the presence of artificial heart valves, deep venous thrombosis, pulmonary embolism, antiphospholipid syndrome and, occasionally, after heart attacks (myocardial infarction).

Dosing of warfarin is complicated by the fact that it is known to interact with many commonly-used medications and even with chemicals that may be present in certain foods. These interactions may enhance or reduce warfarin's anticoagulation effect. In order to optimize the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required by blood testing (INR). During the initial stage of treatment, checking may be required daily; intervals between tests can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose.

Warfarin interacts with many commonly-used drugs, and the metabolism of warfarin varies greatly between patients. Some foods have also been reported to interact with warfarin. Apart from the metabolic interactions, highly protein bound drugs can displace warfarin from serum albumin and cause an increase in the INR. This makes finding the correct dosage difficult, and accentuates the need of monitoring; when initiating a medication that is known to interact with warfarin (e.g. simvastatin), INR checks are increased or dosages adjusted until a new ideal dosage is found.

Many commonly-used antibiotics, such as metronidazole or the macrolides, will greatly increase the effect of warfarin by reducing the metabolism of warfarin in the body. Other broad-spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel, which make significant quantities of vitamin K, thus potentiating the effect of warfarin. In addition, food that contains large quantities of vitamin K will reduce the warfarin effect. Thyroid activity also appears to influence warfarin dosing requirements; hypothyroidism (decreased thyroid function) makes people less responsive to warfarin treatment, while hyperthyroidism (overactive thyroid) boosts the anticoagulant effect. Several mechanisms have been proposed for this effect, including changes in the rate of breakdown of clotting factors and changes in the metabolism of warfarin.

Excessive use of alcohol is also known to affect the metabolism of warfarin and can elevate the INR. Patients are often cautioned against the excessive use of alcohol while taking warfarin.

Between 2003 and 2004, the UK Committee on Safety of Medicines received several reports of increased INR and risk of hemorrhage in people taking warfarin and cranberry juice. Data establishing a causal relationship is still lacking, and a 2006 review found no cases of this interaction reported to the FDA; nevertheless, several authors have recommended that both doctors and patients be made aware of its possibility. The mechanism behind the interaction is still unclear.

The following drugs which increase anticoagulant effects of Warfarin:
  • Allopurinol Amiodarone
  • Amitriptyline
  • Aspirin
  • Azapropazone
  • Bezafibrate R
  • Cefaclor
  • Celecoxib
  • Ciprofibrate
  • Ciprofloxacin
  • Clarithromycin
  • azithromycin
  • Clopidogrel
  • Dexamethasone
  • Dextropropoxyphene
  • Diclofenac
  • Dipyridamole
  • Erythromycin
  • Esomeprazole
  • Fenofibrate
  • Fluoxetine
  • Fluvastatin
  • Ibuprofen
  • Influenza vaccine
  • Itraconazole
  • Ketoconazole
  • Lansoprazole
  • Mefenamic acid
  • Metronidazole
  • Miconazole
  • Mirtazepine Ofloxacin
  • Omeprazole
  • Orlistat
  • Paracetamol
  • Penicillin
  • Phenytoin
  • Piroxicam
  • Prednisolone
  • Rosuvastatin
  • Sibutramine
  • Simvastatin
  • Tamoxifen
  • Thyroid Hormones
When the following drugs decrease anticoagulant effects of Warfarin:
  • Azathioprine
  • Carbamazepine
  • Dexamethasone
  • Phenobarbitone
  • Phenytoin
  • Prednisolone
  • Raloxifene
  • Rifampicin
  • Vitamin K
Over the last several years, there has been increasing focus on avoidable medical errors, especially avoidable medication errors. Although warfarin is a drug that has been on the market for many years and has significant use in the medical community, it remains a drug that can put a patient at risk for an adverse drug event.

  • NHSSB Prescribing Support Team; Nov 2006. ( )

  • Administrative Claims Analysis of the Relationship Between Warfarin Use and Risk of Hemorrhage Including Drug-Drug and Drug-Disease Interactions; KUI ZHANG, MD; CHRISTOPHER YOUNG, PhD; and JAN BERGER, MD ( )
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