Warfarin

Question 1

Drug class
Warfarin

Answer 1

Anticoagulant

Question 2

MOA
Warfarin

Answer 2

Vitamin K antagonist; inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and the antithrombotic factors protein C and protein S.

Question 3

Indication
Warfarin

Answer 3

• Prevention and treatment of VTE
• Prevention of thromboembolism in patients with prosthetic heart valves
• Prevention of stroke in patients with previous MI and increased embolic risk
• AF and a high risk of stroke or systemic embolism

Question 4

Precautions
Warfarin

Answer 4

• Alcoholism—contraindicated.
• Compliance likely to be poor—avoid unless administration is supervised.
• Protein C or protein S deficiency—increases risk of skin necrosis.
• Risk of bleeding

Question 5

Adverse effects
Warfarin

Answer 5

bleeding

Question 6

Counselling
Warfarin

Answer 6

• Always take the same brand of tablets.
• Take tablets at about the same time every day
• Regular INR blood tests
• Stable vitamin K intake - warfarin affected by vitamin K

Question 7

Practice points
Warfarin

Answer 7

• the different brands have not been shown to be bioequivalent and should not be interchanged
• warfarin has a narrow therapeutic range; many drugs interact with warfarin and may decrease its efficacy or increase the risk of bleeding; it is prudent to monitor the INR when changing drug treatment

Question 8

Advantages of NOACs over Warfarin

Answer 8

• Lower rates of intercranial bleeds and strokes
• No routine lab monitoring
• Fewer drug interactions
• Fewer food interactions

Question 9

Disadvantages of NOACs over Warfarin

Answer 9

• Higher cost
• lack of availablity of reversal agent
• Increased risk of GI bleed
• Higher rate of VTE with poor compliance
• No clear efficacy in cancer patients

Question 10

Drug interactions
Warfarin

Answer 10

EVERYTHING!!!

aspirin + warfarin
Combination increases risk of bleeding (as well as antiplatelet effect, aspirin causes GI bleeding and doses of 2–4 g daily have a direct hypoprothrombinaemic effect); avoid combination (except low-dose aspirin in selected patients at high risk for thromboembolism where close monitoring is required).

corticosteroids + warfarin
Corticosteroids may increase warfarin’s anticoagulant effect, increasing the risk of bleeding; monitor INR and decrease warfarin dose if necessary.

fibrates + warfarin
Fibrates may increase warfarin’s anticoagulant effect and risk of bleeding; monitor INR and decrease warfarin dose if necessary.

flucloxacillin + warfarin
Flucloxacillin may decrease warfarin’s anticoagulant effect; monitor INR within the first 3 days of flucloxacillin treatment and increase warfarin dose if necessary.

NSAIDs + warfarin
All NSAIDs (including selective COX‑2 inhibitors) increase the risk of serious GI bleeding. Nonselective agents (antiplatelet effect) and selective COX‑2 inhibitors (may increase INR) may further increase the risk of bleeding; avoid combination if possible or monitor regularly (INR and clinically). Combination with ketorolac is contraindicated.

SSRIs + warfarin
SSRIs may increase anticoagulant effect and risk of bleeding; monitor INR and decrease warfarin dose as needed.

St John’s wort + warfarin
St John’s wort increases metabolism of warfarin, decreasing its anticoagulant effect; avoid combination.

statins + warfarin
Fluvastatin, rosuvastatin and simvastatin may increase warfarin’s anticoagulant effect, increasing the risk of bleeding; consider using atorvastatin or pravastatin (do not appear to interact with warfarin) or decrease the warfarin dose according to INR.

tetracyclines + warfarin
Tetracyclines may increase warfarin’s anticoagulant effect, occasionally causing bleeding; monitor INR within the first 3 days of tetracycline treatment and decrease warfarin dose if necessary.

vitamin K + warfarin
Vitamin K decreases warfarin’s anticoagulant effect by increasing synthesis of blood clotting factors; patients should keep their dietary vitamin K intake constant. Vitamin K is used to reverse bleeding caused by excessive anticoagulation.