- ACRONYMS AND DEFINITIONS
- CAD - Coronary artery disease
- CV - Cardiovascular
- DVT - Deep vein thrombosis
- PAD - Peripheral artery disease
- PE - Pulmonary embolism
- VTE - Venous thromboembolism (DVT and PE)
- FACTOR Xa INHIBITORS
Apixaban (Eliquis®)
Dosage forms
Tablet
- 2.5 mg
- 5 mg
30-day starter pack for VTE treatment
- Contains seventy-four 5 mg tablets
- Has 2 blister cards with dosing instructions
Dosing
Atrial fibrillation
- 5 mg twice a day
- The recommended dose of apixaban is 2.5 mg twice daily in patients with any 2 of the following characteristics:
- Age ≥ 80 years
- Body weight ≤ 132 pounds (60 kg)
- Serum creatinine ≥ 1.5 mg/dl
- May take without regard to food
VTE treatment
- 10 mg twice a day for 7 days, then 5 mg twice a day
- No dose adjustment recommended in kidney disease
- May take without regard to food
VTE secondary prevention
- 2.5 mg twice a day after at least 6 months of treatment
- No dose adjustment recommended in kidney disease
- May take without regard to food
DVT prophylaxis following hip or knee surgery
- 2.5 mg twice a day starting 12 - 24 hours after surgery
- Hip replacement: 35 days of therapy
- Knee replacement: 12 days of therapy
- No dose adjustment recommended in kidney disease
- May take without regard to food
Generic / Price
- NO/$$$$Other
- See switching between other anticoagulants for recommendations on changing to and from apixaban
- Tablets may be crushed and suspended in 60 ml of D5W for delivery via nasogastric tube
Edoxaban (Savaysa®)
Dosage forms
Tablet
- 15 mg
- 30 mg
- 60 mg
Dosing
Atrial fibrillation
- CrCl > 95 ml/min: Not recommended✝
- CrCl 51 - 95 ml/min: 60 mg once daily
- CrCl 15 - 50 ml/min: 30 mg once daily
- CrCl < 15 ml/min: DO NOT USE
- May take without regard to food
- ✝In the ENGAGE study, edoxaban 60 mg once daily was not as effective in patients with CrCl > 95 ml/min
VTE treatment (after 5 - 10 days of parenteral anticoagulant)
- CrCl > 50 ml/min: 60 mg once daily
- CrCl 15 - 50 ml/min: 30 mg once daily
- CrCl < 15 ml/min: - DO NOT USE
- Weight ≤ 132 lbs (60 kg): 30 mg once daily
- With certain P-gp inhibitors (see drug interactions below): 30 mg once daily
- May take without regard to food
- Before starting Edoxaban, patients should be treated for 5 - 10 days with a parenteral anticoagulant
Generic / Price
- NO/$$$$Other
- See switching between other anticoagulants for recommendations on changing to and from edoxaban
Rivaroxaban (Xarelto®)
Dosage forms
Tablet
- 2.5 mg
- 10 mg
- 15 mg
- 20 mg
30-day starter pack for VTE treatment
- Contains 42 tablets of 15 mg and 9 of 20 mg
Oral suspension
- 155 mg bottle
- 1 mg/ml after reconstitution
- Store at room temp
Dosing
NOTE: All dosing presented here is for adults. See Xarelto PI [sec 2.2] for pediatric dosing
Atrial fibrillation
- CrCl > 50 ml/min: 20 mg once daily with evening meal
- CrCl ≤ 50 ml/min: 15 mg once daily with evening meal
VTE treatment
- CrCl ≥ 15 ml/min: 15 mg twice a day with food for 21 days, then 20 mg once daily with food
- CrCl < 15 ml/min: DO NOT USE
- Take at the same time each day
VTE secondary prevention
- CrCl ≥ 15 ml/min: 10 mg once daily, after at least 6 months of standard anticoagulant treatment
- CrCl < 15 ml/min: DO NOT USE
- May take without regard to food
DVT prophylaxis following hip or knee surgery
- CrCl ≥ 15 ml/min: 10 mg once daily starting 6 - 10 hours after surgery once hemostasis has been established
- CrCl < 15 ml/min: DO NOT USE
- Hip replacement: 35 days of therapy
- Knee replacement: 12 days of therapy
- May take without regard to food
VTE prevention in acutely ill medical patients not at high risk for bleeding
- CrCl ≥ 15 ml/min: 10 mg once daily in hospital and after hospital discharge, for a total recommended duration of 31 to 39 days
- CrCl < 15 ml/min: DO NOT USE
- May take without regard to food
- High risk for bleeding defined as any of the following: history of bronchiectasis, pulmonary cavitation, or pulmonary hemorrhage, active cancer (i.e. undergoing acute, in-hospital cancer treatment), active gastroduodenal ulcer in the three months prior to treatment, history of bleeding in the three months prior to treatment, or dual antiplatelet therapy
Reduction of risk of major cardiovascular events in patients with CAD
- 2.5 mg twice daily
- Should be given with aspirin 75 - 100 mg once daily
- No dose adjustment necessary in kidney disease
- May take without regard to food
Reduction of risk of major thrombotic vascular events in PAD, including patients after lower extremity revascularization due to symptomatic PAD
- 2.5 mg twice daily
- Should be given with aspirin 75 - 100 mg once daily
- No dose adjustment necessary in kidney disease
- When starting therapy after a successful lower extremity revascularization procedure, initiate once hemostasis has been established
- May take without regard to food
Missed doses
- 2.5 mg twice daily dosing: take a single 2.5 mg dose as recommended at the next scheduled time
- 15 mg twice daily dosing: take missed dose immediately to ensure intake of 30 mg/day. Two 15 mg tablets may be taken at once.
- 20 mg, 15 mg, or 10 mg once daily dosing: take missed dose immediately. The dose should not be doubled within the same day to make up for a missed dose.
Generic / Price
- NO/$$$$Other
- See switching between other anticoagulants for recommendations on changing to and from rivaroxaban
- Tablets may be crushed and mixed with applesauce. 15 mg and 20 mg tablets should be followed with food.
- Tablets may be crushed and suspended in 50 ml of water for administration via gastric tube. 15 mg and 20 mg tablets should be followed with enteral feedings.
- Crushed and suspended tablets (in water or applesauce) are stable for up to 4 hours.
- Kidney disease dosing
- See dosing above
- Liver disease dosing
- Apixaban (Eliquis®)
- Child-Pugh A: no adjustment necessary
- Child-Pugh B: has not been studied. No dosage recommendation given.
- Child-Pugh C: DO NOT USE
- Edoxaban (Savaysa®)
- Child-Pugh A: no adjustment necessary
- Child-Pugh B/C: DO NOT USE
- Rivaroxaban (Xarelto®)
- Child-Pugh A: no adjustment necessary
- Child-Pugh B/C: DO NOT USE
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- All Factor Xa inhibitors
- Drugs that increase the risk of bleeding - drugs that inhibit coagulation may increase the risk of bleeding when taken with Factor Xa inhibitors
- Drugs that may increase the risk of bleeding include:
- Anagrelide (Agrylin®)
- Aspirin
- Direct thrombin inhibitors (dabigatran)
- Factor Xa inhibitors (e.g. rivaroxaban, apixaban)
- Fish oil (e.g. Vascepa®)
- P2Y12 inhibitors (e.g. clopidogrel, ticagrelor, prasugrel)
- NSAIDs (e.g. ibuprofen, naproxen)
- SSRIs and SNRIs (e.g. fluoxetine, venlafaxine)
- Vorapaxar (Zontivity®)
- Warfarin (Coumadin®)
- Apixaban (Eliquis®)
- Drugs that are combined P-glycoprotein inhibitors and CYP3A4 strong inhibitors
- Apixaban is a substrate of P-glycoprotein and CYP3A4
- Drugs that are combined P-glycoprotein inhibitors and CYP3A4 strong inhibitors may increase apixaban levels
- For patients receiving apixaban doses of 5 or 10 mg twice a day, reduce the dose by 50% when taken with these drugs
- In patients who are already taking 2.5 mg twice a day, these medications should not be taken with apixaban
- Examples of p-glycoprotein inhibitors that are also CYP3A4 strong inhibitors include ketoconazole, itraconazole, and ritonavir
- One exception to the recommendation is clarithromycin. Pharmacokinetic data suggest that no dose adjustment is necessary when clarithromycin is given with apixaban.
- Drugs that are combined P-glycoprotein inducers and CYP3A4 strong inducers
- Apixaban should not be taken with drugs that act as both P-glycoprotein inducers and CYP3A4 strong inducers because exposure to apixaban is greatly reduced
- Examples of these medications include rifampin, carbamazepine, phenytoin, and St John's wort
- Edoxaban (Savaysa®)
- Certain P-glycoprotein inhibitors - Edoxaban dosing for the treatment of DVT and PE should be 30 mg once daily when taken with the following P-glycoprotein inhibitors:
- Verapamil
- Quinidine
- Azithromycin
- Clarithromycin
- Erythromycin
- Itraconazole
- Ketoconazole
- P-glycoprotein inducers - edoxaban is a p-glycoprotein substrate, and p-glycoprotein inducers may decrease its exposure. Do not combine edoxaban with rifampin. Other p-glycoprotein inducers may also lower exposure.
- Rivaroxaban (Xarelto®)
- Drugs that are combined P-glycoprotein inhibitors and CYP3A4 strong inhibitors
- Rivaroxaban is a substrate for P-glycoprotein and CYP3A4 and should not be taken with drugs that act as both P-glycoprotein inhibitors and CYP3A4 strong inhibitors. Rivaroxaban blood levels and bleeding risk may increase.
- The manufacturer states that Erythromycin (E.E.S®, Ery-tab®) and Clarithromycin (Biaxin®) are exceptions and may be administered with rivaroxaban
- Examples of these medications include:
- Ketoconazole (Nizoral®)
- Itraconazole (Sporanox®)
- Lopinavir and Ritonavir (Kaletra®)
- Ritonavir (Norvir®)
- Indinavir (Crixivan®)
- Conivaptan (Vaprisol®)
- Drugs that are combined P-glycoprotein inducers and CYP3A4 strong inducers
- Rivaroxaban should not be taken with drugs that act as both P-gp inducers and CYP3A4 strong inducers
- Blood levels of rivaroxaban may decrease
- Examples of these medications include:
- Carbamazepine (Tegretol®)
- Phenytoin (Dilantin®)
- Rifampin
- St. John's Wort
- Drugs that are combined P-glycoprotein inhibitors and CYP3A4 moderate inhibitors in patients with decreased kidney function (CrCl ≤ 80 ml/min)
- In patients with decreased kidney function (CrCl ≤ 80 ml/min), rivaroxaban should not be taken with drugs that are combined P-glycoprotein inhibitors and CYP3A4 moderate inhibitors unless the potential benefit outweighs the risk
- While increases in rivaroxaban exposure can be expected under such conditions, results from an analysis in the ROCKET AF trial, which allowed concomitant use with combined P-glycoprotein and weak or moderate CYP3A4 inhibitors did not show an increase in bleeding in patients with CrCl 30 to < 50 mL/min (HR 1.05, 95%CI [0.77 - 1.42])
- Metabolism and clearance
- Apixaban (Eliquis®)
- CYP3A4 - major substrate
- P-glycoprotein - substrate
- BCRP - substrate
- CYP2J2 - minor substrate
- CYP1A2 - minor substrate
- CYP2C8 - minor substrate
- CYP2C9 - minor substrate
- CYP2C19 - minor substrate
- Edoxaban (Savaysa®)
- CYP3A4 - minor substrate
- P-glycoprotein - substrate
- Rivaroxaban (Xarelto®)
- CYP3A4 - substrate
- CYP2J2 - substrate
- P-glycoprotein - substrate
- BCRP - substrate
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $151
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
Patient Assistance Programs for Factor Xa Inhibitors | ||||
---|---|---|---|---|
Drug | Manufacturer | Ships to | PAP info | Application |
Apixaban (Eliquis®) | Bristol-Myers Squibb | Patient or doctor | Link | Link |
Edoxaban (Savaysa®) | Daiichi-Sankyo | Use at pharmacy | Savings card program | N/A |
Rivaroxaban (Xarelto®) | Johnson and Johnson | Pharmacy | Link | Link |
- BIBLIOGRAPHY
- Manufacturer's package insert