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PK/PD
Drug Interactions
Dosing and Adjustments
Miscellaneous 1
Miscellaneous 2
100
Factor Xa inhibitor which is most heavily reliant on renal excretion.
What is Edoxaban (50%), FYI: DOAC = dabigatran (80%)
100
The two primary enzyme systems responsible for drug interactions with the DOACs (must name sub-type if applicable).
What are P-glycoprotein and CYP450 3A4
100
Apixaban for acute DVT/PE, normal renal function.
What is 10mg BID x 7 days, 5mg BID thereafter
100
Apixaban pregnancy category
What is B (no adverse events observed in animal reproducti n studies)
100
MOA of rivaroxaban, apixaban, edoxaban, and dabigatran (provide MOA for each, “DOAC” not acceptable
Direct Factor Xa inhibitors (riva, apix, edox), Factor IIa/Thrombin inhibitor (dabigatran)
200
DOAC is removed the most by hemodialysis in comparison to the others.
What is Dabigatran (50-60% per four-hour session). FYI: others considered negligible (rivaroxaban <1%, apixaban 7%, edoxaban 9%) - correlates with protein binding.
200
Name two medications (not classes) responsible for pharmacodynamic interactions with DOACs (drugs that increase bleeding risk).
What are ASA, NSAIDs, other anticoagulants, P2Y12 inhibitors, GpIIbIIIa inhibitors, etc.
200
Apixaban for reduction in risk of recurrence after 6 months of treatment for DVT/PE
What is 2.5mg BID
200
2. TS is a 28 YOF with history of hypertension and type 2 diabetes. He currently takes valsartan 160mg PO daily, metformin XR 2000mg PO daily and liraglutide 1.8mg SubQ once daily. He is newly diagnosed with atrial fibrillation and is placed on metoprolol tartrate 25mg PO BID for heart rate control. Additionally, with a CHADS-VASc score of 3, it is decided that she will be placed on anticoagulation with a DOAC. Her CBC is WNL, and CrCl is calculated at 105mL/min (SCr 0.8). Please provide your recommendation for this patient (drug, dose, route, frequency). Additionally, provide any recommendations of DOACs she should avoid.
What is Rivaroxaban 20mg PO daily with food, Dabigatran 150mg PO BID, Apixaban 5mg PO BID. Avoid edoxaban (CrCl >95mL/min)
200
DOACs that require initial treatment with a parenteral anticoagulant when treating DVT/PE.
What is Edoxaban, Dabigatran. 5-10 days.
300
DOAC that is least reliant on renal excretion, labeling recommendations include severe renal impairment and ESRD.
What is Apixaban (27%). Dabigatran 80%, rivaroxaban 36%, edoxaban 50%.
300
Drugs that induce P-glycoprotein result in _________ concentrations of DOACs, leading to _______ efficacy.
What is Decreased, Reduced
300
Dabigatran for treatment of acute DVT/PE, normal renal function.
What is 150mg BID
300
Case scenario: GG is a 68 YOM undergoing total hip arthroplasty (THA). At home, he is taking lisinopril, metformin, glipizide, aspirin, atorvastatin, and omeprazole. He will be sent home with 3 weeks of anticoagulation s/p surgery. All labs/vitals are within normal limits. Provide your recommendation including drug, dose, route, frequency.
What is a. Dabigatran 110mg x once then 220mg PO daily, Rivaroxaban 10mg PO daily, or Apixaban 2.5mg PO BID FYI: dabigatran has no indication for TKA, Edoxaban would be inappropriate as it does not have an indication for orthopedic surgery
300
DOAC with relatively fewest pharmacokinetic drug interactions compared to the others. (HINT: only P-glycoprotein inducer interactions – avoid with rifampin).
What is Edoxaban – no interactions with P-glycoprotein inhibitors (dose reduction associated with reduced edoxaban blood levels, therefore, no dose adjustment)
400
DOAC that is a pro-drug that is converted in vivo to its active moiety.
What is Dabigatran.
400
Drugs that inhibit CYP3A4 result in drug interactions with these two DOACs. Inhibition of this enzyme system may result in ________ concentrations of these DOACS, and _________ safety.
What is Rivaroxaban, Apixaban; increased, reduced
400
Rivaroxaban for atrial fibrillation, CrCl 40mL/min
What is 15mg once daily with evening meal (15-50mL/min)
400
Rivaroxaban must be taken with food to enhance absorption, except at this/these dose(s).
What is 10mg. FYI: 15mg or above, must take with food (administer with evening meal). Absorption only 66% when not taken with food at higher doses. F=90% under normal conditions.
400
WM is a 65 YOF with h/o AFib for which she was taking dabigatran 150mg PO BID to reduce the risk of stroke. She received notification from her insurance company that they are no longer going to cover dabigatran, so her doctor decides to switch her to apixaban (which her insurance does cover). She presents to your pharmacy with a prescription for apixaban 5mg PO BID at 1pm in the afternoon. She asks you when she should start taking it and states she took her last dose of dabigatran this morning at 9:00am. What do you tell her?
What is 9:00pm tonight, next scheduled dose
500
DOAC medication that must not be crushed or chewed as it increases the bioavailability by 75%, resulting in an increased bleeding risk.
What is Dabigatran (F=7%).
500
One medication that induces P-glycoprotein and one that inhibits P-glycoprotein, potentially leading to relevant drug interactions with the DOACs.
What is: -Inducers: rifampin, phenytoin, carbamazepine, St. Johns wort -Inhibitors: amiodarone, dronedarone, ketoconazole (systemic), clarithromycin, verapamil, quinidine
500
Edoxaban for atrial fibrillation, CrCl = 110mL/min
What is contraindicated > 95mL/min, higher rates of stroke/systemic embolism
500
A patient is taking rivaroxaban 15mg BID x 21 days for initial VTE treatment. You are working the evening shift as a community pharmacist. The patient calls you at ~6:00pm and states he forgot to take his morning dose (which he takes at 9:00am) and is wondering what to do. What do you tell him?
What is take a dose immediately (may take 30mg together), resume therapy the following day as previously taken. Acceptable: take dose now and at 9:00pm; or take 30mg now.
500
Reversal agent for dabigatran that neutralizes anticoagulant effect by binding to dabigatran with ~350x the affinity of thrombin. Generic name.
What is Praxbind (idaracizumab): IV 5g, administer as 2 doses, no more than 15 minutes apart, Fab, neutralizes effect within minutes; consider activated charcoal, HD removes as well (50-60%)