2. Warfarin Flashcards
Warfarin
MOA
Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and therefore reduce the synthesis of active clotting factors
Warfarin
0.5mg tablet colour
White
Warfarin
1mg tablet colour
Brown
Warfarin
3mg tablet colour
Blue
Warfarin
5mg tablet colour
Pink
Warfarin
How long to start working in body? (Hrs)
48-72hrs
Warfarin LD
5mg 1-2 days
Then
3-9mg OD
everyday on the same time
How to take warfarin
1 full glass of water
Never double the dose
Always carry yellow book
Warfarin
What to monitor (6)
INR on first day, the alternate days then longer up to 12 weeks
Liver function
Renal function
Full blood count
BP
thyroid function
Warfarin
Target INR
Normal
VTE, AF, MI, cardioversion
Recurrent DVT or PE
- 1 or less
- 5
- 5
Warfarin
Target INR which condition?
- 1 INR
- 5 INR
- 5 INR
Normal
VTE, AF, MI, cardioversion
Recurrent DVT or PE
Warfarin
Duration
Isolated calf-vein DVT
Venous thromboembolism PROVOKED by surgery
Or other risk: combined pill, plaster cast or pregnancy
Unprovoked DVT or PE
6 weeks
3 months
3 months + (may be required long term)
Warfarin
Warning ⚠️
Report ASAP
May need antidote
- Haemorrhage
Nosebleeds Bruising Bleeding wounds Haemorrhage stroke (Headache, confusion)
- DVT or PE
(Pain, swelling, tenderness in calf; SOB, chest pain, red skin) - Rash, skin necrosis, purple toes
- Diarrhoea- Vomiting
Warfarin
Antidote
Phytomenadione
(Vit k)
Slow IV 5mg
Warfarin in
Pregnancy
Baby?
Avoid and caution in first trimester,
Best avoided but if benefit Overweight risk only given in 3rd trimester
Babies of mothers taking warfarin at the time of delivery need to be offered immediate prophylaxis with intramuscular phytomenadione (vitamin K1).
Warfarin
Breastfeeding
Not present in milk in significant amounts and appears safe.
Risk of haemorrhage which is increased by vitamin K deficiency.
Warfarin
Hepatic impairment
In general, manufacturers advise caution in mild to moderate impairment;
avoid in severe impairment.
Warfarin
Renal impairment
Use with caution in mild to moderate impairment.
Monitoring
In severe renal impairment, monitor INR more frequently.
Warfarin
+
Vitamin K
Reduced anticoagulant effect
Warfarin
+
Vitamin E
Increased anticoagulant effect
Warfarin
Interaction
Increased and decreased plasma concentration (2)
Corticosteroids
Cholestyramine
Clopidogrel
Warfarin
Interaction with underlying conditions
Enhanced ⬆️ plasma concentration) (9
Hyperthyroidism
Low vitamin K intake
Poor nutritional state
Diarrhea
Liver disease
Congestive heart failure
Cancer
Connective tissue diseases
High fever
Warfarin
Interaction enhanced plasma concentration (⬆️ bleeding risk)
Drugs
Amiodarone Paracetamol Anabolic steroids Azithromicin Cephalogrel Cimetidine Clarithromicin Clopidogrel High dose corticosteroids Cranberry juice Dipyridamole Erythromycin Esomeprazole Fibrates Fluconazole Fluvastatin Itraconazole Methylphenidate Metronidazole Miconazole (including topical use) NSAIDs Omeprazole Propafenone Rosuvastatin SSRIs St John Wort Tamoxifen Testosterone Thyroid hormones Tetracyclines Tramadol Venlafaxine
Warfarin
Interaction (reduced plasma concentration ⬇️= clot risk)
Acictretin Azathioprine Carbamazepine Clopidogrel Griseofulvin Mercaptopurine Phenobarbital Phenytoin Rifamycin Succalfate Vitamin k
Warfarin
+
Surgery
Elective
Elective:
Stop warfarin 5 days before surgery
Give oral Vit K (phytonadione) surgery day
If INR >1.5
Restart warfarin on evening or next day
Warfarin
+
Surgery
Emergency
Delay dose by 6-12hrs
If can’t delay give IV phytonadione + dried prothrombin complex
Warfarin
High risk VTE
+
Surgery
If had VTE in last 3 months
OR
AF/TIA/mechanical valve
Stop warfarin 24hrs before surgery
Treat with:
“Bridge”
Lmwh dose I stress of warfarin
Warfarin
+
Surgery
High risk bleeding
LMWH 48 hrs AFTER surgery
Anticoagulants
SE
passing blood in your urine. passing blood when you poo or having black poo. severe bruising. prolonged nosebleeds. bleeding gums. vomiting blood or coughing up blood. heavy periods in women.
Anticoagulants
Examples
dabigatran (= direct thrombin inhibitor)
edoxaban (= direct Xa factor inhibitors)
rivaroxaban
Apixaban
warfarin
Warfarin and birth
Take warfarin
After 48 hours of postpartum
Warfarin half-life
40 hrs
Warfarin form
Only Tablets
Warfarin
Why CI in pregnancy especially 1st trimester
Crosses placenta
Half life:
dabigatran (= direct thrombin inhibitor)
edoxaban (= direct Xa factor inhibitors)
rivaroxaban
Apixaban
warfarin
dabigatran 13hrs
edoxaban 10-14hrs
rivaroxaban young adult: 5-9hrs/ elderly: 13hrs
Apixaban 12 hrs
warfarin 40 hrs
Dabigatran
Apixaban
Rivaroxaban
Indicated in?
Prophylaxis of venous thromboembolism
following total knee replacement surgery
Edoxaban
Indication
Tx and prophylaxis of DVT
Stroke, non vascular AF
Dose adjustments due to interactions
Manufacturer advises max. dose of 30 mg once daily with concurrent:
ciclosporin,
dronedarone,
erythromycin
ketoconazole
Warfarin
INR 5-8
And
NO bleed
Withhold 1-2 doses
Reduce maintenance dose
Check INR in 2-3 days
Warfarin
INR >8
And
NO bleed
Stop warfarin
Take oral phytonadione
Repeat if INT still high after 24hrs
Restart warfarin if INR =5 or less
Warfarin
INR 5-8 or INR >8
And
bleed
Stop warfarin
IV phytonadione
Repeat if INR still high in 24hrs
Restart warfarin when INR =<5
heparin
Antidote
Protamine
Heparin
Eliminated through?
Renal
Warfarin
Eliminated by?
Hepatic (liver)
Warfarin
can cause a serious skin rash
What is it called?
IMMEDIATE REFERRAL!!!!
Calciphylaxis (kal-sih-fuh-LAK-sis)
is a serious, uncommon disease in which calcium accumulates in small blood vessels of the fat and skin tissues.
Calciphylaxis causes blood clots, painful skin ulcers and may cause serious infections that can lead to death
Rivaroxaban
Catheter after surgery when to take it out?
When to start given it after Removing the catheter
Wait atleast 18hrs after rivaroxaban dose to remove the catheter;
Wait 6 hrs after catheter removed and then give next rivaroxaban dose
