Pharmacology of Oral Anticoagulants 2 Flashcards
What are advantages of DOACs
No routine monitoring, rapid onset, fixed dosing
What are the DOACs
Dabigatran, Rivaroxaban, Apixaban, Edoxaban
Which of the DOACs is a prodrug
Dabigatran
What are characteristics of Dabigatran
Selective,relative, direct thrombin II inhibitor, fixed dose, favors drug dissolution in a acidic environment but preservers gut absorption even when gastric pH is high
What converts dabigatran into the active form
esterases in the plasma and the liver
What is the onset and half life of Dabigatran
2-3 hours, 12-17 hours
T/F: Food affects bioavailability and peak plamsa concentrations of Dabigatran
False: Food does NOT affect the bioavailabiltiy of dabigatran but delays time of peak plasma concentrations by 2 hours
How is Dabigatran eliminated through the body, how does this affect those with certain impairments
90-95% eliminated in the urine unchanged, moderate or severe decline in renal function may prolong excretion rates, elevate plasma concentrations, and increase half life
T/F: Dabigatran is metabolized by CYP 450
False: Dabigatran is NOT metabolized by CYP 450
What medical treatment could possibly remove Dabigatran
Hemodialysis
T/F: INR cannot be used to change the dose of Dabigatran
True
What are the contraindications for Dabigatran
Active pathological bleeding, serious hypersensitvity reactions
What is the dosing for Dabigatran in DVT and PE
5-10 days of parental anticoagulation then 150 mg twice daily (can’t be given if CrCl is less than 30)
What type of drugs should be avoided when someone is taking Dabigatran
Pg-p inducers and inhibitors
What are Pg-p inducers, what happens when co-administered with Dabigatran
Rifampin, Avasimibe, Carbamazepine, Phenytoin, St. John’s wort, Tipranavir/ritonavir/ reduce drug concentration and increase risk of failure
What are Pg-p inhibitors, what happens when co-administered with Dabigatran
Dronaderone and Ketoconazole/ an increased risk of bleeding
What is the age that puts adults at higher risk of bleeding, side effect that should be discussed
Greater than 75 years, Dyspepsia
T/F: Because dabigatran cannot be actively tested it is important to emphasize that a patient is adherent to the medication
True
Which DOAC is a selective, reversible direct inhibitor of Factor Xa
Rivaroxaban (Xarelto)
What are important characteristics of Rivaroxaban (Xarelto)
Doesn’t require a cofactor (such as anti-thrombin III) for activity, by inhibiting FXa decreases thrombin generation, no direct affect on thrombin aggregation but indirectly inhibits platelet aggregation induced by thrombin
What is unique about rivaroxaban bioavailability, how
Dose dependent/ 10 mg dose not affected by food, higher than 10 mg it must be taken with food to increase Cmax and mean AUC
T/F: Rivaroxaban is affected by P-gp drugs and is highly protein bound at over 90%
True
What is Rivaroxaban metabolized by
CYP 3A4
What is the dosing for Rivaroxaban for treatment of DVT and/or PE
15 mg twice a day with food for 21 days followed by 20 mg once daily with food for the remaining treatment
What is the dosing for Rivaroxaban for reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE,prophylaxis of DVT after hip or knee surgery
10 mg with or without food daily
What DOAC is a selective inhibitor of Factor Xa
Apixiban (Eliquis)
T/F: Apixiban also does not require antithrombin 3 activity and does not use INR/PT for dose adjustments
True
T/F: Just like Rivaroxaban, Apixiban bioavailabilty is affected by food
False: Apixiban bioavailability is not affected by food
How is Apixiban metabolized, protein binding
CYP 3A4, around 87%
What are drug interactions that Apixiban (Eliquis) has that increase concentration, how can this be alieviated
Ketoconazole, Itraconazole, Ritonavir/Reduce dose by 50%
What are drug interactions that Apixiban (Eliquis) has that decrease concentration
Rifampin, Barbiturates, Carbamezapine. Phenytoin, St. John’s Wort
What is the least popular Factor Xa inhibitor
Edoxaban (Savaysa)
What is Edoxaban peak, bioavailability, and half life
1-2 hours, 62%, 10-14 hours
What is a unique contraindication for using Edoxaban
Cannont be used if CrCl is greater than 95
Which DOAC is approved for patients hospitalized with an acute medical illness who are at risk for VTE
Betrixiban
Which DOACs need a parenteral lead in
Dabigatran and Edoxaban
Which DOACs have a dosing frequency of once a day, which starts off as twice a day
Rivaroxaban and Edoxaban, Rivaroxaban
T/F: DOACs and Warfarin should never be used while a patient is pregnant or breastfeeding
True
Which DOAC cannot be crushed and mixed with food
Dabigatran
What is the reversible agent for Dabigatran/ Rivaroxaban, Apixaban, Edoxaban
Idarucizumab/Andexanet alfa
When using DOACs what values should be monitored
CBC, Scr, Drug-drug interactions
