DOACs and Warfarin Flashcards
name the DOACs
rivaroxaban, edoxaban, apixaban, dabigatran
rivaroxiban brand name
xarelto
apixaban brand name
eliquis
edoxaban brand name
savaysa
dabigatran brand name
pradaxa
dabigatran indications
NVAF, VTE prophylaxis (orthopedic surgery), treatment of VTE & risk of reduction of recurrence
rivaroxaban indications
NVAF, VTE prophylaxis, treatment of VTE, reduction in risk of recurrence of DVT/PE in pts @ continued risk, reduction in risk of major CV events (death, MI, stroke) in chronic CAD or PAD
apixaban indications
NVAF, VTE prophylaxis (orthopedic surgery), treatment of VTE and reduction in risk of recurrence)
edoxaban indications
NVAF, treatment of DVT and PE
what is the apixaban dosing for NVAF
5 mg po bid
what is the apixaban dosing for NVAF if pt is older than 80, weighs less than 60 kg, or has serum creatinine greater than 1.5
2.5 mg po bid
do DOACs require bridging like warfarin?
NO!
overdosing DOACs doubles risk of ____
bleeding
underdosing DOACs causes a 5-fold increased risk of _____
stroke
which DOACs can we use in patients who weigh more than 120 kg or have BMI over 40 (OBESE)
rivaroxaban or apixaban
which anticoagulants have safer profile: DOACs or warfarin
DOACs
adverse effects of DOACs
bleeding (GI hemorrhage)
adverse effects specific to dabigatran
dyspepsia, nausea
contraindications to DOACs
active major bleed, advanced CKD (CrCL <15) except apixaban, and CrCL<30 mL/min for VTE prophylaxis/treatment
what types of drug-drug interactions exist for DOACs
P-glycoprotein and CYP3A
strong P-gp inhibitors ____ DOAC concentrations
increase
what are some strong P-Gp inhibitors
ketoconazole, itraconazole, clarithyromycin, dronedarone, amiodarone, verapamil, quinidine, cyclosporine, conivaptan, ritonavir, lopinavir, indinavir
strong P-gp inducers ____ DOAC concentrations
decrease
what are some strong p-gp inducers
rifampin, carbamazepine, phenytoin, St. John’s wort
Strong CYP3A inhibitors _____ DOAC concentrations
increase
what are some strong CYP3A inhibitors
azole antifungals, macrolides, protease inhibitors
strong CYP3A inducers _____ DOAC concentrations
decrease
what are some strong CYP3A inducers
rifampin, carbamazepine, phenytoin, st. john’s wort
dabigatran and edoxaban are metabolized by __
P-gp
apixaban and rivaroxaban are metabolized by ___
CYP3A and P-gp
what are the DOAC trial exclusions in NVAF
mechanical heart valves, hemodynamically significant mitral stenosis, advanced CKD, significant liver disease, recent stroke (7-14 days), pregnancy/lactation, severe HTN, reversible causes of AFib
what are the guidelines for pregnancy w/ anticoagulants
no DOACs. warfarin is teratogenic in first 2 trimesters, use enoxaparin. can use warfarin in 3rd trimester
reversal agent/antidote for dabigatran
idaracizumab (praxbind)
what is the reversal agent FDA approved for apixaban and rivaroxaban
coagulation factor Xa (andexxa)
all DOACs are at least ____ to warfarin for reducing risk of stroke/systemic embolism
not inferior
which DOACs are superior to warfarin for risk of stroke/ systemic embolism
dabigatran 150 mg and apixaban
all DOACs reduce the risk of ____ versus warfarin
major bleeding
you should withhold DOACs for ____ prior to procedure depending on bleed risk and kidney function
24-48 hours
after initiating warfarin, there is a ______ state
hypercoagulable
explain how warfarin causes a hypercoagulable state when first initiated
it also depletes some of your body’s own natural anticoagulants like protein c and protein s
how do we allow for a slow onset of warfarin since there is a hypercoagulable state?
use a parenteral to bridge for 3-5 days
warfarin interferes with _____ dependent clotting factors
vitamin k
the protein target of warfarin is ____
VKORC1 (vitamin K oxide reductase 1)
VKORC1 is the enzyme responsible for ___
activation of clotting factors that depend on vitamin K as a cofactor
VKORC1 oxidizes the reduced form of Vit K, and carboxylates the inactive clotting factors to make them ___
active
warfarin is a ___ mixture
racemic (r and s isomers)
warfarin is highly bound to ____
albumin (95%)—> drug interactions
the r isomer of warfarin is metabolized by ___
CYP3A4
the s isomer of warfarin is metabolized by ___
CYP2C9
how do you monitor warfarin
INR
what drug interactions with warfarin would INCREASE inr (risk for bleed)
alcohol, amiodarone, anabolic steroids, cimetidine, clarithromycin, cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, miconazole, omeprazole, phenylbutazone, piroxicam, propafenone, propranolol, vit. E
what drug interactions with warfarin would DECREASE INR (risk for clot)
barbiturates, carbamazepine, chlordiazepoxide, cholestyramine, nafcillin, rifampin, sucralfate, dicloxacillin, azathioprine, cyclosporine, trazodone, vit K
is a loading dose necessary for most patients starting warfarin
NO
what is the initial dose for warfarin
2-5 mg daily
bridge warfarin with ______ for 4-5 days
heparin
how do you adjust the dose of warfarin
10-15% of weekly dose
adverse effects of warfarin
bleeding, skin necrosis, purple toe
indications for warfarin
DVT, PE, prevention of systemic embolism (stroke)—> biprosthetic heart valves short term, acute MI, LV dysfunction, LV thrombus, AFib, mechanical prosthetic valve (mitral), mechanical prosthetic valve (aortic)
what is the therapeutic INR range for warfarin
2-3
what is the therapeutic INR range for warfarin if indication is mechanical mitral prosthetic valve
2.5-2.5
patient counseling points for warfarin
signs of bleed, signs of clot, INR monitoring and dosage, tablet identification, common drug interactions, consistent intake of dietary vitamin k
what are the reversal agents for warfarin
vitamin k (phytonadione), fresh frozen plasma, prothrombin complete concentrates like profilnine (3 factor) and kcentra (4 factor), recombinent factor VIIa (novoseven)
what is the target of dabigatran
thrombin (factor IIa)
what is the target of apixaban
Xa
what is the target of rivaroxiban
Xa
what is the target of edoxaban
Xa
