Trade name(s): MAREVAN, COUMADIN® Drug Class:Anticoagulant
Pharmacological action: What it does: Warfarin inhibits clotting in the body How it does it: competitively inhibits vitamin K epoxide reductase which is needed to regenerate vitamin k in the body. Lack of vitamin K means clotting factors 10 9 7 and 2 are not produced in the liver. Therefore reduced clotting
Pharmacokinetics:
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Absorption: Readily absorbed in GI tract.
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Distribution: High protein binding.
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Metabolism: Metabolised in the liver into inactive metabolites.
Warfarin is a mixture of enantiomers which are metabolised by different CYPP450 cytochromes. R-warfarin is metabolised primarily by CYP1A2 and CYP3A4. S- warfarin is metabolised primarily by CYP2C9. The efficacy of warfarin is affected primarily when the metabolism of S-warfarin is altered.
- Excretion: Warfarin is mainly excreted in the urine in the form of its metabolites.
Indications: prophylaxis and or treatment of venous thrombosis and pulmonara embolism, thromboembolism because of atrial fibrillation and is adjunct with the prevention of systemic embolism after an MI
Contraindications: Any condition where the hazard from haemorrhage is greater then the benefit from anticoagulation
- Hypersensitivity to warfarin
- Haemorrhagic stroke or bleeding related to active ulceration or overt bleeding
- Within 72 hours of major surgery
- 48 hours post partum
- Pregnancy 1st and 3rd trimesters
- Fibrinolytic drugs
Adverse reactions: Mostly from overcooking dose. Haemorrhage and bleeding in general.
Surgery should not be performed under warfarin.
Interactions: Other Antiplatelets and anticoagualants: clopidogrel, NSAIDS, Thrombin inhibitors, hepatin inhibitors Herbal products (such as St. Johns wort, Natto, dashen, Dong quai) reduce the effects of warfarin.
Antialzheimers MABS: donanemab, Lecanemab, lessen warfarins effects
Drugs which are metabolised by CYPP450, CYP1A2, CYP3A4, CYP2C9 will alter the the plasma levels of warfarin.
Additionally antibiotics which alter gut microflora (where vitamin K is synthesised) may alter effects of warfarin. orlistat changes absorption on Vit K in the intestine and will also alter the effects
Direct acting antivirals can change liver function and may alter production of clotting factors.
Vitamin K antagonists may also increase INR and need to be taken into account.
Higher levels of alcohol consumption may alter the rate of metabolism of warfarin (large consumption = impair, chronic heavy = induce)
Cranberry and grapefruit products have been known to alter INR and should be taken into account
Dosing/Current guidelines: Dosing is individualised and is altered to get patients INR to reach target range
Prevention and treatment of thromboembolism
- Adult: 5-10 mg once daily on day 1 followed by 5 more mg on day 2 then adjust to bring INR into target range. Usual maintenance dose is around 1-10 mg daily.
Low dose for prevention of thromboembolism in elderly patients with AFib
- Adult: 3mg once daily for 2 days then adjust to INR
Monitoring: It is important to review the need for warfarin on a regular basis as ADRs are common.
INR should be determined daily until stabilisation within target range at which loger testing intervals are appropriate. However with patients who are at very high risk INR monitoring should be done often anyways
Overdose: If the patient is present within 1 hour of ingestion of (OD level of) warfarin consider activated charcoal.
In the case of serious haemorrhage, stop warfarin and give prothrombin complec (incl. factors 10 9 7 2), or fresh frozen plasma.
Where there is no haemorrhage give slow IV injection os phytomenadione (Vit K) 10-20 mg for adults.
Monitor INR for when to resume typical treatment.
Pregnancy: warfarin crosses the placenta.
Subsidy: PHARMAC fully subsidses this drug in its tablet form.
What to tell patients:
- Read the additional information given with this medicine
- Take at the same time each day, e.g. in the evening
Comments/Observations/notes: