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Drug Interactions of Anticoagulants – Part 6
(Drug Interactions of Argatroban)
Dr. P.NAINA MOHAMED PhD
Pharmacologist
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)
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
effects
Increased risk
bleeding Contraindicated
Argatroban & Heparin
If coadministration is required, closely monitor the patient for signs and symptoms of bleeding.
Argatroban +
Heparin
Additive
anticoagulation
Increased risk of
bleeding
Argatroban & Other Anticoagulants
Use caution and monitor closely for bleeding when Argatroban is used concomitantly with other Anticoagulants.
Argatroban + Other Anticoagulants
(Heparin, Enoxaparin, Dalteparin,
Tinzaparin, Bivalirudin, Lepirudin,
Fondaparinux, Phenindione,
Danaparoid, Rivaroxaban, Apixaban,
Dabigatran)
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
effectsIncreased 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 plateletsIncreased 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
by platelets
Decreased function of
plateletsIncreased 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
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
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
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
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
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
Anticoagulant
+ 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, 9eKaren 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 C. Armstrong
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/DrugReference/Druginteractionchecker/