drug interactions of dabigatran
TRANSCRIPT
Drug Interactions of Anticoagulants – Part 7(Drug Interactions of Dabigatran)
Dr. P.NAINA MOHAMED PhDPharmacologist
Introduction
Anticoagulants are the drugs used to prevent harmful blood clots which can cause serious conditions like Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), or a Stroke, by affecting blood coagulation factors.
Interaction between one or more coadministered medications leading to change in their effectiveness or toxicity, is termed as “Adverse drug interaction”.
Anticoagulants can interact with prescription drugs, Over-the-counter (OTC) medications, Herbal products, Dietary supplements, Vitamins, Foods, Diseases, and Genetics (family history).
Anticoagulants Coumarins (Oral) Warfarin, Acenocoumarol, Dicoumarol, Ethyl biscoumacetate, Phenprocoumon Indandiones (Oral) Phenindione, Fluindione Factor Xa inhibitors Fondaparinux sodium, Rivaroxaban (Oral) Heparin Low Molecular Weight Heparins (LMWH) Enoxaparin, Dalteparin, Tinzaparin, Bemiparin, Certoparin, Nadroparin, Parnoparin, Reviparin Heparinoids Danaparoid, Dermatan sulphate, Pentosan polysulfate, Suleparoid, Sulodexide Direct Thrombin inhibitors Hirudins - Bivalirudin, Desirudin, Lepirudin Synthetic Thrombin Inhibitors – Argatroban Dabigatran etexilate (Oral)
Dabigatran & Itraconazole or Ketoconazole
https://products.boehringer-ingelheim.com/pradaxa/using-pradaxa/contraindications
Dabigatran + Itraconazole or Ketoconazole
Inhibition of P-glycoprotein-mediated
efflux transport of Dabigatran
Defibrotide & Antithrombotics
Concomitant use of defibrotide and a systemic antithrombotic agent is contraindicated.
http://www.bloodjournal.org/content/120/21/3411?sso-checked=true
Antithrombotics +
Defibrotide
Additive antithromboti
c effects
Dabigatran & Ticagrelor
Concomitant use should be avoided in patients with severe renal impairment.http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/022512Orig1s023ltr.pdf
Dabigatran + Ticagrelor
Ticagrelor inhibits P-glycoprotein-mediated efflux
transport of Dabigatran
Increased dabigatran exposure
Dabigatran & P-gp Inducers
Concomitant use of dabigatran and a P-gp inducer should be avoided.https://www.nps.org.au/australian-prescriber/articles/p-glycoprotein-and-its-role-in-drug-drug-interactions
Dabigatran + P-Glycoprotein Inducers
(Carbamazepine, Rifampin, St. John's
wort)
Induction of P-gp-mediated efflux
transport of dabigatran
Dabigatran & P-gp Inhibitors
When dabigatran is used for reducing the risk of stroke and systemic embolism in non-valvular atrial fibrillation, avoid coadministration of a P-gp inhibitor in patients with severe renal impairment
http://spo.escardio.org/eslides/view.aspx?eevtid=48&fp=129
Dabigatran + P-gp inhibitors (Verapamil, Quinidine, Amiodarone,
Ketoconazole, Itraconazole, Ritonavir, Saquinavir, Nelfinavir, Tacrolimus,
Cyclosporine)
Inhibition of P-gp-mediated efflux transport of dabigatran
Increased dabigatran exposure Increased risk of bleeding
Dabigatran & Other
Anticoagulants
Use caution and monitor closely for bleeding when Dabigatran is used concomitantly with other Anticoagulants.
Dabigatran + Other Anticoagulants
(Heparin, Enoxaparin, Dalteparin, Tinzaparin, Bivalirudin, Lepirudin,
Fondaparinux, Phenindione, Danaparoid,
Rivaroxaban, Apixaban)
Additive anticoagulation
Increased risk of bleeding
Anticoagulants & Fibrinolytics
Observe patients for external bleeding and be alert for signs and symptoms of internal bleeding, if concomitant use of an anticoagulant and a fibrinolytic agent is required.
https://www.ncbi.nlm.nih.gov/pubmed/11085346
Anticoagulants + Fibrinolytics
(Alteplase, Retaplase, Tenecteplase, Streptokinase,
Urokinase)
Additive anticoagulation
Increased risk of bleeding
Anticoagulants & Antiplatelet agents
Concomitant use warrants close monitoring.http://circ.ahajournals.org/content/116/3/305
Anticoagulants + Antiplatelet
agents (Aspirin, Clopidogrel,
Ticagrelor, etc)
Additive anticoagulation
Increased risk of bleeding
Anticoagulants & Fenofibrate
Reduce the dose of the anticoagulant by about one-third at the start of treatment, if concomitant use is required.
Then gradually adjust the dose based on the results of INR monitoring.https://www.ncbi.nlm.nih.gov/pubmed/12549950
Anticoagulants +
Fenofibrate
Additive effects on
anticoagulation
Anticoagulants & Orlistat
Caution should be exercised when Anticoagulants and Orlistat are used concurrently.
https://www.ncbi.nlm.nih.gov/pubmed/12659605
Anticoagulants + Orlistat
Orlistat may reduce the absorption of
fat-soluble vitamins, including
vitamin K
Increased risk of bleeding
Anticoagulants & NSAIDs
If used concomitantly, monitor for signs of bleeding.http://www.aafp.org/afp/2009/1215/p1371.html
Anticoagulants + NSAIDs (Ibuprofen,
Diclofenac, Naproxen, etc)
NSAIDs possess antiplatelet effects
Increased risk of bleeding
Anticoagulants & SSRIs
Serotonin is essential in initiating the hemostatic response of platelets to vascular injury. Monitor patient for signs of increased bleeding When SSRIs and an anticoagulant are
given concurrently. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728939/
Anticoagulants + Selective serotonin reuptake inhibitors
(SSRIs) (Fluvoxamine, Paroxetine,
Vortioxetine, Escitalopram, Sertraline, Nefazodone,
vilazodone)
SSRIs block the uptake of serotonin by platelets
Anticoagulants & SNRIs
Serotonin is essential in initiating the hemostatic response of platelets to vascular injury. Monitor patient for signs of increased bleeding When SNRIs and an anticoagulant are
given concurrently. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728939/
Anticoagulants + Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
(Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran,
Levomilnacipran, Sibutramine)
SNRIs block uptake of serotonin by platelets
Anticoagulants & St. John's Wort
Prothrombin time should be monitored closely. Patients should not discontinue St. John's Wort without notifying their
health care provider.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917631/
Anticoagulants + St.John's
Wort
St. John's Wort induce CYP3A4 and CYP1A2 mediated
metabolism of R-warfarin and CYP2C9 mediated S-warfarin
metabolism
Anticoagulants & Ginkgo
Extreme caution is advised, due to the severity of the bleeding cases reported.
http://onlinelibrary.wiley.com/doi/10.1002/mnfr.200700098/epdf
Anticoagulants + Ginkgo
Ginkgolide B of Ginkgo may inhibit Platelet
Activating Factor (PAF) induced platelet
aggregation
Anticoagulants & Garlic
Monitor bleeding time and signs and symptoms of excessive bleeding, if garlic is taken with an anticoagulant.
http://onlinelibrary.wiley.com/doi/10.1002/mnfr.200700072/epdf
Anticoagulants + Garlic
Garlic has Anti-platelet,
Antithrombotic and Fibrinolytic activities
Increased risk of bleeding
Anticoagulants + Papaya
The patient should be monitored closely for symptoms of bleeding and the INR should be closely monitored, if taken concomitantly.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025393/
Anticoagulants + Papaya
Papain of Papaya may damage the mucous membranes of the
gastrointestinal tract
Anticoagulants & Chamomile
Patients should be educated about the potential risk of using chamomile products, while being treated with warfarin.
Monitor the patient for signs and symptoms of excessive bleeding.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435958/
Anticoagulants + Chamomile (Matricaria
chamomilla)
Coumarins present in chamomile may
potentiate the effect of anticoagulants
Anticoagulants & Coenzyme Q10
Caution is advised if coenzyme Q10 and Anticoagulants are taken together. Monitor the INR to determine continued therapeutic effect.https://www.ncbi.nlm.nih.gov/pubmed/9621803
Anticoagulants + Coenzyme
Q10
Coenzyme Q10 is chemically similar
to Vitamin K2
Anticoagulants & Ginger
Caution is advised if ginger and an anticoagulant are taken concomitantly.
https://www.ncbi.nlm.nih.gov/pubmed/11144706
Anticoagulants + Ginger
Ginger may inhibit thromboxane B2
formation & may increase prostacyclin levels
Increased risk of bleeding
Anticoagulants & Fenugreek
Monitor bleeding time and signs and symptoms of excessive bleeding, if fenugreek and anticoagulants are used concomitantly.
http://onlinelibrary.wiley.com/doi/10.1592/phco.21.5.509.34492/epdf
Anticoagulants +
Fenugreek
Coumarin content of fenugreek may add to the effect of anticoagulants
Anticoagulants & Anise
Caution is advised if anise is taken with an anticoagulant. Monitor for signs and symptoms of increased excessive bleeding.
http://www.ajhp.org/content/57/13/1221.long
Anticoagulants + AniseCoumarin content of
Anise may add to the effect of
anticoagulants
Anticoagulants & Clove Oil
Monitor the patient closely for signs and symptoms of bleeding, if both are taken together.
http://www.ajhp.org/content/57/13/1221.long
Anticoagulants + Clove Oil
Eugenol and Acetyl eugenol in clove oil
inhibit platelet aggregation
Increased risk of bleeding
Anticoagulants & Asafetida
Monitor the patient closely for signs and symptoms of bleeding.http://www.ajhp.org/content/57/13/1221.long
Anticoagulants + Asafetida
Asafetida contains free ferulic acid and coumarin
derivatives
Anticoagulants & Capsaicin
Signs and symptoms of excessive bleeding should be monitored closely if capsaicin (or large amounts of red pepper) and anticoagulants are taken concomitantly.
http://article.sciencepublishinggroup.com/pdf/10.11648.j.cmr.20140305.17.pdf
Anticoagulants + Capsaicin
Capsaicin may inhibit platelet aggregation
and enhance fibrinolytic activity
Anticoagulants & Evening primrose
oil
Monitor for signs and symptoms of excessive bleeding.https://www.ncbi.nlm.nih.gov/pubmed/19783511
Anticoagulants + Evening primrose oil
Gamma-linolenic acid from Evening primrose oil may inhibit thromboxane B2 production and increase prostacyclin production
Increased risk of bleeding
Anticoagulants & Licorice
Monitor for signs and symptoms of excessive bleeding, if licorice is taken with an anticoagulant.
https://www.ncbi.nlm.nih.gov/pubmed/23671711
Anticoagulants + Licorice
Inhibition of thrombin and
platelet aggregation by licorice
Anticoagulants & Celery
Monitor the patient closely for signs and symptoms of bleeding, if both are taken together.
http://naturaldatabase.therapeuticresearch.com/nd/PrintVersion.aspx?id=882&AspxAutoDetectCookieSupport=1
Anticoagulants + Celery
Apigenin content of Celery, may inhibit thromboxane A2 formation
leading to reduced platelet aggregation & Celery contains
coumarin derivatives, which may produce additional anticoagulant
effects
TIPS for Patients on Anticoagulants
Do not double the dose to compensate a missed one. Do not forget to discuss with your surgeon or dentist about the regular use of
Anticoagulant prior to any surgery. Talk to your Physician or Pharmacist before taking any other medications,
including prescription and OTC (Over-The-Counter) medicines. Contact your doctor if you develop severe diarrhea, an infection or a fever. Seek immediate medical advice if there is signs of bleeding such as blood in
your stools or urine, nose-bleeds, bleeding gums, excessive menstrual bleeding or excessive bruising.
Be careful with knives and try to minimize the risk of falling. Always adhere to the prescribed dosage schedule. Wear or carry an identification stating that You are on Anticoagulant.
Conclusion
Drug interactions can result in significant morbidity and mortality and thus minimizing the risk for drug interactions should be a goal in drug therapy.
The patients with clotting disorders should bring a list of all of the drugs they are taking including prescription drugs, over-the-counter drugs, and any supplements, herbal or otherwise, during their visit to the doctor or pharmacist.
The risk of adverse effects could be reduced by healthcare professionals through the screening, education, and follow up on suspected drug interactions.
If possible, the patients are recommended to fill all their prescriptions at one pharmacy.
Pharmacists can play a crucial role in identifying possible drug interactions by asking patients on Anticoagulants about their herbal and other alternative medicine product use.
References
Stockley’s Drug Interactions, 9e Karen Baxter Goodman & Gilman's: The Pharmacological Basis of
Therapeutics, 12e Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmann Basic & Clinical Pharmacology, 12e Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor A Manual of Adverse Drug Interactions J.P. Griffin, P.F. D'Arcy Clinical Manual of Drug Interaction Principles for Medical
Practice Gary H. Wynn, . Jessica R Oesterheld, . Kelly L Cozza, . Scott CArmstrong
References http://www.micromedexsolutions.com http://
reference.medscape.com/drug-interactionchecker https://www.drugs.com/drug_interactions.html http://www.webmd.com/interaction-checker/ http://
www.rxlist.com/drug-interaction-checker.htm http://
umm.edu/health/medical/drug-interaction-tool http://ukhealthcare.uky.edu/Library/DrugReferenc
e/Druginteractionchecker/