DOAC for VTE Direct Oral Anticoagulants Clint Shedd DNP, FNP-BC Emory University
No disclosures Direct Oral Anticoagulants
Understand VTE and the ACCP s position on it List the DOACs available in the US Summarize common dosing regimens for DOACs Evaluate drug interactions and special considerations related to DOACs
In general: major general surgery; major orthopedic surgery; lower-extremity paralysis due to spinal cord injury; fracture of the pelvis, hip or long bones; multiple trauma; malignant diseases (breast, lung, brain, pelvis, rectum, pancreas, and GI) or chemo In pregnancy: prior VTE; genetic predisposition; obesity; prolonged immobility; multiple births; increased maternal age; cancer and serious infection Other: prior VTE; age; cardiac or respiratory failure; immobility; oral contraceptives; inherited or acquired thrombophilias
We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. Quality of evidence: Evidence from randomized, controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise), or very strong evidence from observational studies.
In patients with proximal DVT or pulmonary embolism (PE), we recommend long-term (3 months) anticoagulant therapy VTE: CHEST Feb. 2016: In patients with DVT of the leg or PE and no cancer, as long-term (first 3 months) anticoagulant therapy, we suggest dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonist (VKA) therapy (all Grade 2B) In patients with DVT of the leg or PE and cancer ( cancerassociated thrombosis ), as long-term (first 3 months) anticoagulant therapy, we suggest LMWH over VKA therapy or DOAC therapy
In patients with a proximal DVT of the leg or PE provoked by surgery, treat with anticoagulation for 3 months In patients with a proximal DVT of the leg or PE provoked by a nonsurgical transient risk factor, treat with anticoagulation for 3 months In patients with an unprovoked DVT of the leg or PE, treat with anticoagulation for at least 3 months In patients with a first unprovoked VTE (proximal DVT of the leg or PE) and who have low or moderate bleeding risk, we suggest extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy In patients with a second unprovoked VTE and who have a low bleeding risk, we recommend extended anticoagulant therapy
DOACs: what s out there? Dabigatran (Pradaxa): direct thrombin inhibitor Rivaroxaban (Xarelto): Xa Apixaban (Eliquis): Xa Edoxaban (Savaysa): Xa Betrixaban
Which of the following has a reversal agent for its anticoagulant effect? A. Dabigatran (Pradaxa) B. Rivaroxaban (Xarelto) C. Apixaban (Eliquis) D. Edoxaban (Savaysa)
Which of the following has a reversal agent for its anticoagulant effect? A. Dabigatran (Pradaxa) B. Rivaroxaban (Xarelto) C. Apixaban (Eliquis) D. Edoxaban (Savaysa)
Increased risk of bleeding Should avoid NSAIDs Monitor Hgb and LFTs yearly CrCl regularly if reduced (q 3-6 months)
Reversal: Tricky; idarucizumab for dabigatran, but others Dialysis doesn t clear them either Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.
Pregnancy Category B: apixaban (and enoxaparin too, btw) but apixaban not recommended in pregnancy Pregnancy Category C: dabigatran, rivaroxaban, edoxaban Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and wellcontrolled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Which of the following should be taken with food? A. Dabigatran (Pradaxa) B. Rivaroxaban (Xarelto) C. Apixaban (Eliquis) D. Edoxaban (Savaysa)
Which of the following should be taken with food? A. Dabigatran (Pradaxa) B. Rivaroxaban (Xarelto) C. Apixaban (Eliquis) D. Edoxaban (Savaysa)
DVT and PE treatment: 15 mg twice daily for 21 days, then 20 mg once daily Post-op prophylaxis for knee or hip replacement: 10 mg daily for up to 35 days Don t use if prosthetic heart valve, CrCl less than 30 Avoid use in patients with Child-Pugh B and C hepatic impairment or with any degree of hepatic disease associated with coagulopathy
Avoid concomitant use of rivaroxaban with combined P- gp and strong CYP3A4 inhibitors like ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir, and conivaptan Avoid concomitant use of rivaroxaban with drugs that are combined P-gp and strong CYP3A4 inducers like carbamazepine, phenytoin, rifampin, St. John s wort Also no grapefruit juice, of course
P-gp +/- CYP3A4 interaction Amiodarone CrCl > 80 ml/min CrCl 15-80 ml/min Caution Carbamazepine Avoid use Avoid use Clarithromycin Avoid use Avoid use Conivaptan Avoid use Avoid use Diltiazem Caution Avoid use Dronedarone Caution Avoid use Erythromycin Caution Avoid use Felodipine Caution Indinavir/ritonavir Avoid use Avoid use
P-gp +/- CYP3A4 interaction CrCl > 80 ml/min CrCl 15-80 ml/min Itraconazole Avoid use Avoid use Lopinavir/ritonavir Avoid use Avoid use Phenytoin Avoid use Avoid use Quinidine Ranolazine Caution Caution Rifampin Avoid use Avoid use Ritonavir Avoid use Avoid use St. John s wort Avoid use Avoid use Verapamil Caution Avoid use
Instructions for Patient Use Remind patients to not discontinue rivaroxaban without first talking to their healthcare professional. Advise patients with DVT and/or PE to take rivaroxaban 15 mg or 20 mg tablets with food at approximately the same time every day Advise patients who cannot swallow the tablet whole to crush rivaroxaban and combine with a small amount of applesauce followed by food If a dose is missed, advise the patient to take rivaroxaban as soon as possible on the same day and continue on the following day with their recommended daily dose regimen.
The anticoagulant effect of rivaroxaban cannot be monitored with standard laboratory testing or readily reversed. Anti-Xa testing for rivaroxaban? Converting to or from VKA, parenteral anticoagulation, or d/c ing pre-surgery?
Which of the following is taken once daily? A. Dabigatran (Pradaxa) B. Apixaban (Eliquis) C. Edoxaban (Savaysa)
Which of the following is taken once daily? A. Dabigatran (Pradaxa) B. Apixaban (Eliquis) C. Edoxaban (Savaysa)
DVT and PE (treatment and recurrence): 150 mg twice daily (after 5 to 10 days of parenteral anticoagulation) Post-op prophylaxis for hip replacement: 110 mg given 1-4 hours after completion of surgery/hemostasis, then 220 mg daily for at least 10-14 days and up to 35 days Don t use if mechanical heart valve, CrCl less than 30
Drug CrCl > 50 CrCl 30-50 Amiodarone usual dose avoid use Clarithromycin usual dose avoid use Dronedarone usual dose avoid use Ketoconazole usual dose avoid use Quinidine usual dose avoid use Rifampin avoid use avoid use Verapamil usual dose avoid use Ticagrelor usual dose avoid use
Generally, the extent of anticoagulation does not need to be assessed. When necessary, use aptt or ECT, and not INR, to assess for anticoagulant activity for converting to or from VKA, parenteral anticoagulation, or d/c ing pre-surgery, see PI
Instructions for Patients Keep dabigatran in the original bottle to protect from moisture. Do not put dabigatran in pill boxes or pill organizers. When more than one bottle is dispensed to the patient, instruct them to open only one bottle at a time. Instruct patient to remove only one capsule from the opened bottle at the time of use. The bottle should be immediately and tightly closed. Advise patients not to chew or break the capsules before swallowing them and not to open the capsules and take the pellets alone. Advise patients that the capsule should be taken with a full glass of water. Dyspepsia common side effect
VTE treatment: 10 mg twice daily for 7 days followed by 5 mg twice daily Prevention of recurrent VTE: 2.5 mg twice daily Ortho: 2.5 mg twice daily In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days.
No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis; BUT: Studies with ELIQUIS did not enroll patients with ESRD on dialysis or patients with a CrCl <15 ml/min. Prosthetic heart valves: ELIQUIS use not recommended.
P-gp +/- CYP3A4 interaction 5 mg or 10 mg 2.5 mg Carbamazepine Avoid use Avoid use Clarithromycin Decrease dose by 50% Avoid use Itraconazole Decrease dose by 50% Avoid use Ketoconazole Decrease dose by 50% Avoid use Phenytoin Avoid use Avoid use Rifampin Avoid use Avoid use Ritonavir Decrease dose by 50% Avoid use
Take apixaban exactly as prescribed by your doctor. Take apixaban twice every day with or without food. Do not change your dose or stop taking apixaban unless your doctor tells you to. If you miss a dose of apixaban, take it as soon as you remember. Do not take more than one dose of apixaban at the same time to make up for a missed dose. If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take apixaban.
VTE treatment: edoxaban 60 mg orally once daily (after 5 to 10 days of initial therapy with a parenteral anticoagulant) 30 mg once daily for patients with CrCL 15 to 50 ml/min or body weight less than or equal to 60 kg or who use certain P-gp inhibitors
Reduced efficacy with CrCl greater than 95 (in A fib only) Not recommended for moderate to severe hepatic impairment Not recommended for mechanical heart valves or moderate to severe mitral stenosis
P-gp interaction CrCl 30-50 ml/min Azithromycin 30 mg QD Clarithromycin 30 mg QD Erythromycin 30 mg QD Itraconazole 30 mg QD Ketoconazole 30 mg QD Quinidine 30 mg QD Rifampin Avoid use Verapamil 30 mg QD
Rivaroxaban: once daily, must take with food, may crush or cut pills Dabigatran: can be reversed, BID dosing, dyspepsia, storage considerations, parenteral first Apixaban: BID dosing, lower dose for extended treatment, may take without food Edoxaban: once daily, not recommended for ortho prophylaxis, may take without food, parenteral first
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