Bleeding with warfarin

DRUG INTERACTIONS As do other NSAIDs, the propionic acid derivatives may interfere with the action of antihypertensive and diuretic agents, increase the risk of bleeding with warfarin, and increase the risk of bone marrow suppression with methotrexate. Ibuprofen also has been... 

Classic examples of Type A reactions are bleeding with warfarin, hypoglycaemia with sulphonylureas and headache with glyceryl-trinitrate. 

Exaggerated therapeutic response at the target site (e.g. bleeding with warfarin)... 

ADRs are certainly the most important form of iatrogenic (i.e. doctor-induced) disease. Many of the serious reactions that occur are well-recognised and potentially preventable - e.g. bleeding with warfarin, the upper gastrointestinal effects of NSAIDs. In public health terms, it is not newly introduced drugs that are responsible for most of the population burden of adverse drugs reactions but those whose safety profile is well-established (see below). 

The principal adverse reaction associated with warfarin is bleeding, which may range from very mild to severe. Bleeding may be seen in many areas of the body, such as the bladder, bowel, stomach, uterus, and mucous membranes. Other adverse reactions are rare but may include nausea, vomiting, alopecia (loss of hair), urticaria (severe skin rash), abdominal cramping, diarrhea, rash, hepatitis (inflammation of the liver), jaundice (yellowish discoloration of the skin and mucous membranes), and blood dyscrasias (disorders). 

Aithal, G.P., Day, C.P., and Kesteven, P.J. et al. (1999). Association of polymorphisms in the cytochrome P450 C YP2C9 with warfarin dose requirement and risk of bleeding comph-cations. Lancet 353, 717-719. 

Stroke Prevention All patients with paroxysmal, persistent, or permanent AF should receive therapy for stroke prevention, unless compelling contraindications exist. A decision strategy for stroke prevention in AF is presented in Fig. 6-9.27 In general, most patients require therapy with warfarin in some patients with no additional risk factors for stroke, aspirin may be acceptable. For some patients, serious consideration of the benefits of warfarin versus the risks of bleeding associated with warfarin therapy is warranted. The potential bleeding risks associated with warfarin may outweigh the benefits in... 

The dose of capecitabine begins at 1250 mg/m2 twice a day when used by itself lower doses are used often when it is given in combination with irinotecan or oxaliplatin or in patients with renal insufficiency. The dose should be taken on a full stomach with breakfast and dinner. Capecitabine administered with warfarin can result in significant increases in the patient s INR and requires close monitoring to prevent bleeding. The convenience of oral administration and an improvement in toxicity make capecitabine a useful alternative to IV 5-FU both by itself and incorporated into other regimens used in colon cancer. 

Clopidogrel may be substituted for aspirin when aspirin is absolutely contraindicated Long-acting nondihydropyridine calcium antagonists instead of /3-blockers as initial therapy ACEIs are recommended in patients with CAD or other vascular disease Low-intensity anticoagulation with warfarin, in addition to aspirin, is recommended but bleeding would be increased Therapies to be avoided include ... 

The most serious interactions with warfarin are those that increase the anticoagulant effect and the risk of bleeding. The most dangerous of these interactions are the pharmacokinetic interactions with the pyrazolones phenylbutazone and... 

Interactions of statins with warfarin, resulting in an increased bleeding tendency, have been reported (51), including interactions of anticoagulants with both lovastatin (51) and fluvastatin (89). 

Sweet clover also contains coumarin derivatives and therefore poses an increased risk of bleeding if given with warfarin. There have been no reports of an interaction between sweet clover and warfarin or hemorrhagic disease in humans. However, several cases of severe hemorrhage and death have been reported in cattle. 

When given in combination with warfarin or thienopyri-dine class of antiplatelet agents the ASA dose is usually lowered to 80 to 100 mg based on a post hoc analysis of data from the clopidogrel in unstable angina to prevent recurrent events (CURE), which showed similar efficacy but less major bleeding with the low dose (< 100 mg) of ASA (38). 

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