The document discusses drug interactions of the anticoagulant argatroban. It notes that argatroban can interact with other anticoagulants, antiplatelets, NSAIDs, SSRIs, SNRIs, St. John's Wort, herbal supplements like ginkgo and garlic, and foods like papaya - increasing the risk of bleeding. It advises close monitoring when argatroban is taken with these substances. The document also provides tips for patients taking anticoagulants and references additional sources on drug interactions.

1. Drug Interactions of
Anticoagulants – Part 6
(Drug Interactions of Argatroban)
Dr. P.NAINA MOHAMED PhD
Pharmacologist

2. 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).

3. 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)

4. 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

5. Argatroban & Heparin
 If coadministration is required, closely monitor the patient for signs and
symptoms of bleeding.
Argatroban +
Heparin
Additive
anticoagulation
Increased risk of
bleeding

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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
platelets
Increased risk of Bleeding

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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&AspxAuto
DetectCookieSupport=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

29. 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.

30. 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.

31. 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 C.
Armstrong

32. 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/Dru
ginteractionchecker/