WARFARIN

(INR)    (bleeding risk)   (while taking warfarin)  (contra-indications)    (vitamin K in food)  (OTC and herbs)   (other medications)

Warfarin ( 'Coumadin' or 'Marevan' ) is an oral anticoagulant taken to reduce the formation of blood clots. It works by preventing the body converting vitamin K into blood clotting proteins. Warfarin is a very effective medication but its action on the body has to be carefully regulated and monitored - too much warfarin may result in life threatening haemorrhage (e.g. from the stomach or into the brain) while inadequate levels will mean treatment is ineffective.
Most of the warfarin ingested is bound to proteins within the blood - it is only unbound warfarin which is effective. Unfortunately there are numerous factors which influence the levels of effective warfarin within an individual from day to day. Factors which increase vitamin K intake (diet), increase protein binding (many medications) or improve liver function ( where clotting proteins are formed) will reduce the effect of warfarin.
Conversely, warfarin activity may be markedly increased by impaired liver function ( especially heart failure and alcohol ) or reduced protein binding (many medications).

The activity of warfarin is measured by the INR - which is the ratio of the time taken for a patient's blood to clot compared with a normal person not taking warfarin. Thus a normal person will have an INR of 1.
The target range for INR depends on the condition being treated - as a guide :
   - atrial fibrillation, deep vein thrombosis,                   
    pulmonary embolus, tissue heart valves                    2.0  to 3.0
   - bi-leaflet aortic  heart valves                                  2.5  to 3.5
   - mechanical high risk heart valves,
    some clotting disorders                                            3.0  to 4.5
Patients at high risk of bleeding, the very elderly and those requiring long term prevention of DVT may have a lower INR target ( 1.5 to 2.0).
The risk of haemorrhage increases as the INR rises above 3 and becomes high with an INR above 5.
Because so many factors affect the INR, blood tests to check the INR must be performed at least every 4 to 6 weeks once treatment has been stabilised, and more often when the situation is not stable.

There are two brands of warfarin available and they are not interchangeable:
'COUMADIN'  
1 mg (tan)    2 mg (lilac)    5 mg (green)
'MAREVAN'      1 mg (brown)    3 mg (blue)    5 mg (pink)
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Patients taking warfarin will bruise and bleed more readily than normal and should :
1 make treating health professionals aware that they are taking warfarin if they are to have any medicines prescribed or have any surgical or dental procedure performed.
2 Avoid taking medication (including over the counter, herbal or natural therapies) without first consulting their doctor.
3 Avoid aspirin or non-steroidal pain killers (e.g. aspirin, Nurofen, Brufen, Voltaren, Advil, Act 3 etc) - paracetamol and Panadeine in normal dose should be safe.
4 Avoid heavy contact sports.
5 Have a regular dietary intake of vitamin K containing foods (see list below).
6 Take their warfarin at the same time each day - usually in the evening.
7 Do not have more than 2 standard alcohol drinks per day.
8 Watch for signs of abnormal bleeding, especially from the bowel (very black or red stools) or in the urine.
9 *Warfarin cannot be taken during pregnancy.

Bleeding risk with warfarin therapy can be predicted by allocating 1 point for each of the relevant factors listed :
[   ] age 65 or more
[   ] previous haemorrhagic stroke
[   ] previous haemorrhage from stomach or bowel (usually from an 'ulcer')
[   ] recent heart attack, significant anaemia, diabetes or significant renal impairment
      
0 points        = low risk
        1 or 2 points = medium risk
        3 or 4 points = high risk
Treatment of haemorrhage due to warfarin or abnormally high INR is with its antidote, vitamin K - usually as a single oral dose, which works quite quickly. Vitamin K would normally be given if the INR is 7 or more, or if there is bleeding. High INRs less than this, in the absence of bleeding, are normally treated by with holding warfarin for a variable time and adjusting its dose.
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Common contra-indications to warfarin therapy include :
- allergy to warfarin
- uncontrolled hypertension
- gastro-intestinal haemorrhage or peptic ulcer
- dementia, a history of falls or alcoholism
- bacterial endocarditis
- bleeding disorders
- cerebral aneurysm or haemorrhage
- haemorrhagic retinopathy (esp diabetic)
- inability to have regular INRs

Adverse reactions to warfarin are usually related to bleeding complications, true allergy is rare. Other rare complications include hair loss (alopecia), skin necrosis, nausea and diarrhoea, purple discolouration of the toes, jaundice and reduced bone mineral density.
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Foods which have a high vitamin K content and should be eaten in a fairly constant intake ( number of stars reflects vit K content)
*****    beetroot
****     broccoli
***      spinach, brussel sprouts, lettuce
**       coleslaw, asparagus, okra
*        tuna canned in oil, green peas, celery, mixed vegetables, canned sauerkraut, french salad dressing
(***      soy milk also markedly reduces warfarin effect)

Herbal and over the counter medications which effect INR (list is not exhaustive!)
Increase INR and bleeding risk
garlic, fenugreek, gingko biloba, glucosamine, cranberry juice, danshea, devil's claw, *dong quai, alfalfa, angelica, aniseed, armica, asafoetida, celery, chamomile, horse chestnut, prickly ash, papaya extract,
quassia, red clover, liquorice, policosanal, saw palmetto, cod liver oil, evening primrose, feverfew, flaxseed, ginger
Reduce INR
ginseng, green tea (large quantities), coenzyme Q10, chlorella, corn silk, stinging nettle, St John's wort
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Medications which interact with warfarin and effect INR (list is not exhaustive!)
Increase INR and bleeding risk

amiodarone (CordaroneX, Aratac))  celecoxib ( Celebrex)           
clarithramycin (Klacid)               erythromycin (Eryc, EES)    
fluvastatin (Vastin, Lescol)        fluvoxamine (Luvox)           
metronidazole (Flagyl)                paracetamol (large doses)   
tamoxifen (Genox)                    miconazole  (Daktarin)                     
tramadol  (Tramal)                     roxithromycin (Rulide, Biaxsig)
mexilitine  (Mexitil)                   itraconazole   (Sporanax)                      
norfloxacin (Noroxin)                 clavunate (Augmentin, Klacid)         
chloramphenicol                         cephalosporins (Keflex, Ceclor, Ibilex)
dexamethasone                          cimetidine (Tagamet)           
fluoxetine (Prozac, Lovan)          sulpha/trimethoprim (Bactrim, Septrin, Triprim)
ciprofloxacin (Ciproxin)               fluconazole (Diflucan)
gemfibrozil  (Jezil)                      simvastatin (Lipex, Zocor, Zimstat)
thyroxine (Oroxine)                     ketoconazole (Nizoral incl lotion)
primidone                                   
Reduce INR
barbiturates                               carbamazepine (Tegretol)    
propylthiouracil (Neomercazole)   rifampicin
griseofulvin (Grisovin)                sucralfate
phenytoin (Dilantin)
other medications that increase bleeding risk
aspirin (Cartia, DBL aspirin, Astrix, Solprin, Aspro Clear etc)
clopidrogel  (Plavix, Iscover)
dipyridamole (Asasantin, Persantin)
non steroidal anti-inflammatories (Voltaren, Naprosyn, Brufen, Nurofen, Orudis, Indocid, Mobic etc)
ticlopidine    (Ticlid)

(note - medications are most likely to cause a problem when they are added, stopped or used intermittently  - when used long term the warfarin dose can often be modified to take the relevant interactions into account)

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