Annotations Potential Drug Interactions
  • Loading dose should be adjusted 25% for patients receiving amiodarone
  • Drug interactions with warfarin may occur via several mechanisms, including impairment of absorption, induction or inhibition of metabolism, competition for protein-binding sites, and platelet inhibition. Drugs that inhibit or induce P-450 2C9 (responsible for metabolism of S-warfarin) may have the greatest effect on INR.
  • Complementary/alternative medications known to have potential to increase warfarin effects include bromelains, danshen, dong quai, garlic, gingko biloba, ginseng and omega 3 fish oil.
  • Complementary/alternative medications known to have potential to decrease warfarin effects include coQ10 and St. John's Wort.
  • INR should be monitored more frequently in pediatric patients who are already on warfarin therapy and are starting on antibiotics.
  • Warfarin dosing can be adjusted to permit use of some medications that have effect on warfarin metabolism. Please consult Hematology for adjustment recommendations.

Commonly used drugs in children that affect INR Values

Drug

INR Effect

Mechanism

Amiodarone

Increase

Decreases warfarin metabolism

Antifungal agents

Increase

Fluconazole, ketoconazole, and miconazole (vaginal) decrease warfarin metabolism

Barbiturates

Decrease

Increase warfarin metabolism

Carbamazepine

Decrease

Increase warfarin metabolism

Cephalosporins

Increase

Inhibits production of vitamin K dependent clotting factors

Ciprofloxacin

Increase

Displace warfarin from binding sites (possible mechanism; not fully known)

Clarithromycin

Increase

Decrease warfarin metabolism

Contraceptives (Oral)

Increase

Increase clotting factor synthesis; may inhibit oxidative metabolism

Corticosteroids

Increase

Produce hypercoagulability; may have ulcerogenic effects

Delaviridine

Increase

May inhibit warfarin metabolism

Erythromycin

Increase

Decrease warfarin metabolism

Ibuprofen

Increase

May inhibit warfarin metabolism in addition to platelet inhibition

Indomethacin

Increase

May inhibit warfarin metabolism in addition to platelet inhibition

Isoniazid

Increase

May inhibit warfarin metabolism

Losartan

Increase

May inhibit warfarin metabolism

Omeprazole

Increase

May inhibit of warfarin metabolism

Metronidazole

Increase

Inhibits metabolism of S-isomer

Nicardipine

Increase

May inhibit warfarin metabolism

Pantoprazole

Increase

May inhibit warfarin metabolism

Penicillins

Increase

May enhance warfarin metabolism; May reduce GI flora synthesis of vitamin K

Phenytoin / fosphenytoin

Decrease

Increase warfarin metabolism; induces warfarin metabolism; displaces warfarin from protein-binding sites; enhances metabolism of clotting factors

Rifampin

Decrease

Induces hepatic enzymes, increases warfarin metabolism

Sulfamethoxazole - Trimethoprim (Bactrim)

Increase

Sulfonamide component may stereo-selectively inhibit S-isomer metabolism

Vitamin K

(ADEK, Centrum, Viactiv)

Decrease

Effects of oral anticoagulants are directly antagonized by the excessive ingestion of foods or dietary supplements containing vitamin K

Zafirlukast

Increase

May inhibit warfarin metabolism

Other important interactions

Drug

Effect

Mechanism

Aspirin, NSAIDs

Increased risk of bleed

Inhibition of platelet aggregation

Anti-platelet agents (dipyridamole, clopidrogel, ticlopidine, cilostazol)

Increased risk of bleed

Inhibition of platelet aggregation

References


These guidelines do not establish a standard of care to be followed in every case. It is recognized that each case is different and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare guidelines for each. Accordingly these guidelines should guide care with the understanding that departures from them may be required at times.

Copyright © 1996-2014 The Children's Mercy Hospital