drug interactions of argatroban

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

http://www.bloodjournal.org/content/120/21/3411?sso-checked=true

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

http://circ.ahajournals.org/content/116/3/305

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.


Anticoagulants +

Fenofibrate

Additive effects on

anticoagulation

Enhanced bleeding

risk


Anticoagulants & Orlistat

Caution should be exercised when Anticoagulants and Orlistat are used concurrently.


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

http://www.aafp.org/afp/2009/1215/p1371.html

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.


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.


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



Anticoagulants & Garlic

Monitor bleeding time and signs and symptoms of excessive bleeding, if garlic is taken with an anticoagulant.


Anticoagulants + Garlic

Garlic has Anti-platelet,

Antithrombotic and

Fibrinolytic activities



Anticoagulants + Papaya

The patient should be monitored closely for symptoms of bleeding and the INR should be closely monitored, if taken concomitantly.


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.


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.


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.


Anticoagulants + Ginger

Ginger may inhibit

thromboxane B2 formation

& may increase

levels



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

http://onlinelibrary.wiley.com/doi/10.1592/phco.21.5.509.34492/epdf

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.


Anticoagulants + Clove Oil

Eugenol and Acetyl

in clove oil inhibit platelet

aggregation



Anticoagulants & Asafetida

Monitor the patient closely for signs and symptoms of bleeding.


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


http://article.sciencepublishinggroup.com/pdf/10.11648.j.cmr.20140305.17.pdf

Anticoagulants & Evening primrose oil

Monitor for signs and symptoms of excessive bleeding.


Anticoagulants + Evening primrose

oil

Gamma-linolenic acid from

primrose oil may inhibit

thromboxane B2 production and

increase prostacyclin production



Anticoagulants & Licorice

Monitor for signs and symptoms of excessive bleeding, if licorice is taken with an anticoagulant.


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

http://naturaldatabase.therapeuticresearch.com/nd/PrintVersion.aspx?id=882&AspxAutoDetectCookieSupport=1

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/

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/

drug interactions of argatroban

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