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Interactions with Oral Anticoagulants

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Marie Sisco

on 27 January 2014

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Transcript of Interactions with Oral Anticoagulants

Interactions with Oral Anticoagulants
Oral Anticogulants
Warfarin (Coumadin®, Jantoven®)
Dabigatran (Pradaxa®)
Rivaroxaban (Xarelto®)
Apixiban (Eliquis®)

Dabigatran (Pradaxa)
Direct thrombin inhibtor

Indication: Stroke prevention in non-valvular AF

Dose: 150mg PO BID

Rivaroxoban (Xarelto)
Factor Xa inhibitor

postoperative thromboprophylaxis
DVT and PE treatment
Reduce DVT and PE recurrence
Stroke prevention in non-valvular AF

Dose: 20 mg PO daily
Class: Direct Factor Xa Inhibitor

Indication: Stroke and systemic embolism prevention in non-valvular atrial fibrillation (AF)

Dose: 5mg PO BID
Warfarin (Coumadin®/Jantoven®)
Drug-drug Interactions
Dual P-gp and CYP 4A4 inhibitors
Ketoconazole, fluconazole, ritonavir, clarithromycin, erythromycin
Avoid concomitant use
Increases exposure
Drug-drug Interactions
Metabolized by CYP3A4
Substrate for P-gp transport
Strong dual inhibitors of CYP3A4 and P-gp
Reduce dose to 2.5 mg PO BID
Drug-drug Interactions
Antiplatelet agents
Monitoring and Reversal
Drug-drug Interactions
Strong dual inducers of CYP3A4 and P-gp
St. John's wort
Avoid concomitant use
Labs: chromogenic anti-Xa
S/S of bleeding
Skin rash/allergic reaction
chest pain/swelling of face
Activated charcoal

Can be taken with or without food
Can be crushed
Patient Education
Do not abruptly stop

It may take longer than usual for bleeding to stop

Call your doctor right away if you experience signs of serious bleeding

If you miss a dose, take it as soon as you can. Do not take double up on doses.
Patient Education
Do not abruptly discontinue

Report any signs of unusual bleeding

Let your doctor know of all the medications you are taking

Report symptoms of thombotic events such as stroke if transitioning to or from warfarin therapy
Vitamin K antagonist


Treatment and prevention of venous thromboembolism (VTE)
Deep venous thrombosis (DVT)
Pulmonary embolism (PE)
Prevent thromboembolic events
Atrial fibrillation
Clotting disorders
Prosthetic heart valves
Initial dose: 5 mg by mouth daily for 1-2 days (Goal INR in 4 -5 days)*

Drug-Drug Interactions

No effect on CYP enzymes

P-glycoprotein interactions

Dronedarone, quinidine, ketoconazole
Can be given with or without food

Do not break, crush, chew, or open up capsule
Dose Adjustments
+ CrCl 30-50 mL/min 75 mg BID
Any P-glycoprotien inhibitor + CrCl < 30 mL/min Avoid concurrent use
May increase exposure by 75%

Increased bleed risk
Patient Education

Proper Administration

Missed dose - 2 doses no closer than 6 h

Signs and symptoms of bleeding

Other adverse effects
Warfarin-Food Interactions
Increase the risk of bleeding
Decrease anticoagulation/INR
Carbamazepine, cholestyramine, phenobartial, phenytoin, primidone, rifampin, vitamin K
Drug-food Interactions
Increase Anticoagulation/INR
, cimetidine, ethanol,
, fluvastatin, fluvoxamine, macrolide antibiotics,
, omeprazole, sertraline, tigecycline,
Dietary Supplement
Cranberry, cat's claw, coenzyme Q10, devil's claw, dong quai, echinacea, garlic, ginseng, glucosamine, grapefruit juice, green tea, milk thistle, primrose oil, St. John's wort, Valerian, willow bark, wintergreen oil
Warfarin Interactions
Increase Bleeding Risk
Unfractionated/low-molecular-weight heparin
Non-steroidal anti-inflammatories (NSAIDs)
Patient Education
Signs and symptoms of bleeding/clot
Drug interactions (OTC products, alcohol)
Maintaining a consistent diet
Tablet strength/color
Missed dose
Monitoring requirements
Drug-Drug Interactions
Dual P-pg and strong CYP3A4 Inducers
Rifampin, phenytoin
Avoid concomitant use
Decreases exposure

Anticoagulants and NSAIDS/Aspirin
Benefit must outweigh risk
Missed Dose
Once daily dosing
Take as soon as possible on same day
Twice daily dosing
Take as soon as possible
May take two 15 mg tabs
Doses >/= 15mg/day need to be given with food

May crush and administer in applesauce

Nasogastric/gastric tube: crush in 50 mL water
followed by enteral feeding
not into small intestine
Dose Adjustments
Depends on INR goal
Do not change dose more than every 3 days
Delayed onset of up to 15 days
Reduce or increase dose by 10-20% (average weekly dose: 30-40 mg)
Takes 5-7 days to see INR level after adjustment
1. Warfarin. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2011 http://clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=6508&sec=moninte&t=0. Updated August 7, 2013. Accessed January 26, 2014.
2. Dabigatran. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2011 http://clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=3547&sec=moninte&t=0. Updated May 17, 2013. Accessed January 23, 2014.
3. Pradaxa [package insert]. Ridgefield, Connecticut: Boehringer Ingelheim Pharmaceuticals; 2010
4. Rivaroxaban. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2011 http://clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=3771&sec=monindi&t=0. Updated January 7, 2014. Accessed January 23, 2014.
5. Xarelto [package insert]. Leverkusen, Germany: Janssen Pharmaceuticals; 2011.
6. Apixaban. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2011 http://clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=3795&sec=moninte&t=0. Updated March 21, 2013. Accessed January 22, 2014.
7. Eliquis [package insert]. Princeton, New Jersey: Bristol-Myers; 2012
Advantages of New Oral Agents
Highly selective
Ability to bind clot-bound coagulation factors
Rapid onset
Predictable pharmacologic profiles
Fixed and convenient dosing regimens
frequent monitoring not required
Denise Bentley, Sandeep Dhokia, Amber Galicki, Marie Varsos
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