Warfarin MOA and pathway effects
Vitamin K antagonistAffects factors 7,9,10,2
What parts of the clotting cascade do UFH and LMWH inhibit?
Xa and Thrombin (IIa) by binding to antithrombin
What drugs are Factor Xa inhibitors?
DIRECT:Rivaroxaban (Xarelto)Apixaban (Eliquis)Edoxaban (Savaysa)Betrixaban INDIRECT:Fondaparinux
What drugs are direct thrombin inhibitors?
IV:argatrobanbivalirudinPO:dabigatran
Heparin dose for prevention of VTE (prophylaxis dose)
5,000 u SQ Q8-12H
Heparin treatment dose for VTE
80 u/kg bolus (5,000 u max)18 u/kg/hr infusion (max 1,000 u/hr)
Heparin AE
BleedingHITincreased potassiumosteoporosis
Reversal agent for Heparin
protamine sulfate
Monitoring for heparin
aPTT
anticoagulants that don't have renal adjustment
heparinWarfarin
anticoagulant of choice in pregnancy
lovenox
Lovenox prophylaxis dose good renal function
30 mg SQ Q12Hor40 mg SQ QD
Lovenox prophylaxis dose CrCl <30
30 mg SQ QD
Lovenox treatment of VTE and UA/NSTEMI --> normal renal and CrCl <30
1 mg/kg Q12H1 mg/kg QD
Lovenox treatment of STEMI for pts <75
30 mg IV bolus + 1 mg/kg SQ x1then, 1 mg/kg SQ Q12H (max 100 mg for first 2 doses)
Lovenox treatment of STEMI for pts >75
0.75 mg/kg Q12H (max 75 mg for first 2 doses)do not give a bolus dose for this patient
Lovenox treatment for STEMI pts with CrCl <30
1 mg/kg SQ QD (same as VTE & NSTEMI)
Lovenox boxed warning
Neuraxial anesthesia
Lovenox CI
History of HITActive major bleed
Lovenox monitoring
Anti-Xa levels
Lovenox reversal agent
Protamine
DOC for HIT
Argatrobanalternates:bivalirudinfondaparinux (off-label)
What antibody mediates HIT
IgG
Apixaban drug class
Factor Xa inhibitor
Apixaban dosing for nonvalvular AFib
Normal: 5 mg BID2.5 mg BID if:- > 80 y/o- body weight < 60 kg- SCr > 1.5
Apixaban dosing for DVT/PE treatment
1) 10 mg BID x 7 days2) then, 5 mg BID
apixaban reversal agent
andexanet alfa
Rivaroxaban class
Factor Xa inhibitor
Rivaroxaban dosing for nonvalvular AFib for each CrCl parameter
CrCl > 50 - 20 mg QD w/ evening mealCrCl 15-50 - 15 mg QD w/ evening mealCrCl < 15 - don't use
Rivaroxaban dosing for VTE treatment
1) 15 mg BID w/ food x21 days2) then, 20 mg QD w/ food
Rivaroxaban dosing for DVT prophylaxis post-hip surgery
10 mg QD
Rivaroxaban reversal agent
andexanet alfa
Fonxaparinux MOA
indirect factor Xa inhibitor (via antithrombin)
Dabigatran dosing for nonvalvular AFib
normal renal fxn: 150 mg BID CrCl 15-30: 75 mg BID CrCl <15: avoid
Dabigatran AE
Dyspepsia gastritis-like symptoms
Which IV direct thrombin inhibitors are used for HIT
argatrobanbivalirudin
dabigatran reversal agent
Idarucizumab (Praxbind)
Warfarin starting dose
10 mg/day x2 days then adjust per INR
How long does warfarin take to start working?
5 days
Warfarin contraindications
pregnancy category X
Warfarin AE
bleedingPurple toe syndrome
Mneumonic for remembering warfarin tablet colors
Please Let Greg Brown Bring Peaches To Your WeddingPink (1 mg)Lavender (2 mg)Green (2.5 mg)Brown/Tan (3 mg)Blue (4 mg)Peach (5 mg)Teal (6 mg)Yellow (7.5 mg)White (10 mg)
warfarin pink tablet
1 mg
warfarin lavender tablet
2 mg
warfarin green tablet
2.5 mg
warfarin brown/tan tablet
3 mg
warfarin blue tablet
4 mg
warfarin peach tablet
5 mg
warfarin teal tablet
6 mg
warfarin yellow tablet
7.5 mg
warfarin white tablet
10 mg
What hepatic enzyme is warfarin a substrate of?
CYP 2C9
What do 2C9 inducers do to a warfarin pt's INR?
Decrease = clotting risk
What are some 2C9 inducers that interact with warfarin metabolism?
- carbamazepine- phenobarbital- phenytoin- rifampin- licorice- St. John's wort
What do 2C9 inhibitors do to a warfarin pt's INR?
increase it = bleeding risk
What are some 2C9 inhibitors that interact with warfarin metabolism?
M - metronidazole, macrolidesA - amiodarone, AzolesT - TMP/SMZ
How to dose adjust for a warfarin patient starting amiodarone?
decrease dose by 30-50%
What are some natural products that increase bleeding risk?
5 GsGingerGarlicGinkoGinsingGlucosamine
Warfarin reversal agent
Vitamin K
What is the proper way to dose protamine for heparin reversal?
1 mg protamine = 100 u heparinheparin has short t1/2, so only reverse the last 2-3 hours worth
What is the proper way to dose protamine for lovenox reversal?
1:1 dosingtreat the last 8 hours
What is the proper way to dose protamine for dalteparin (Fragmin) reversal?
1:100 dosing
How long to treat VTE if caused by a reversible risk factor?
3 months