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Drug Interactions of Anticoagulants – Part 3
(Drug Interactions of Low Molecular weight Heparins (LMWHs))
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 – Argotroban Dabigatran etexilate (Oral)
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 antithrombotic
effectsIncreased risk of bleeding
Contraindicated
LMWHs & Warfarin
If coadministration of Warfarin and Enoxaparin is required, closely monitor the patient for signs and symptoms of bleeding, and neurological impairment in patients who are receiving neuraxial anesthesia or undergoing spinal puncture.
Prothrombin time/INR should also be monitored closely if enoxaparin and warfarin are taken concomitantly, especially during medication initiation or discontinuation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265267/
LMWHs + Warfarin
Additive anticoagulatio
n Increased risk of bleeding
LMWHs & Heparin
If coadministration is required, closely monitor the patient for signs and symptoms of bleeding and neurological impairment in patients who are receiving neuraxial anesthesia or undergoing spinal puncture.
LMWHs + Heparin
Additive anticoagulatio
n Increased risk
of bleeding
LMWHs & Other
Anticoagulants
If coadministration is required, closely monitor the patient for signs and symptoms of bleeding.
LMWHs + Other Anticoagulants
(Danaparoid, Bivalirudin,
Rivaroxaban, Apixaban, Dabigatran)
Additive anticoagulation
Increased risk of bleeding
LMWHs & Antiplatelet agents
Concomitant use warrants close monitoring of signs or symptoms of bleeding.
http://circ.ahajournals.org/content/116/3/305
LMWHs + Antiplatelet
agents (Aspirin, Clopidogrel,
Ticagrelor, etc)
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
Enhanced bleeding risk
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
Decreased function of platelets
Increased risk of Bleeding
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
Decreased function of platelets
Increased risk of Bleeding
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
Decreased warfarin plasma concentrations
leading to Reduced anticoagulant effectiveness
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
Increased risk of bleeding
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
Increased bleeding risk
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
Increased risk of bleeding
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
Reduced anticoagulant effectiveness
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
Increased risk of bleeding
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 + Anise
Coumarin content of Anise may add to the
effect of anticoagulants
Increased risk of bleeding
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
Increased risk of bleeding
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
Increased risk of bleeding
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 Increased risk
of bleeding
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
Increased risk of bleeding
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/
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