acetaminophen

Warfarin Institute of America

DEDICATED TO YOUR HEALTH SINCE 2000

ACETAMINOPHEN INTERACTIONS WITH warfarin (Coumadin, Jantoven)

Brand Names: Tylenol, Feverall, Acephen, Neopap, Apacet, Children's Dynafed Jr. Genapap, Maranox, Mapap, Panadol, Tempra, Aceta, Aspirin Free Pain Relief, Genebs, Meda, Tapanol, Aspirin Free Anacin Maximum Strength, Extra Strength Dynafed E.X. Redutemp Dapacin, Infants' Pain Reliever, Silapap, Ridenol, Oraphen PD, Children's Pain Reliever, Halenol, Liquiprin, Capital with Codeine, Tylenol with Codeine, Acetaminophen with Codeine, Aceta with Codeine, Fioricet with Codeine, Lortab, Zydone, Hydrocodone with Acetaminophen, Bancap HC, Ceta-Plus, Co-Gesic, Duocet, Dolocet, Hydrocet, Hydrogesic, Hydrophen, Margesic - H, Lorcet, Anexsia, Panacet, Stagesic, T-Gesic, Vicodin, Norco, DHC Plus, Acetaminophen with Oxycodone, Percocet, Roxicet, Roxilox, Tylox, Propoxyphene Napsylate with Acetaminophen, Darvocet N, Propacet 100, Wygesic, and many other brands. There are so many that they could not all be listed here. If you are taking warfarin (Coumadin, Jantoven), you should read the label of any pain relief medication to determine if it contains acetaminophen. If you are unsure, purchase the product at a pharmacy where you can have the pharmacist check the label for you.

Acetaminophen is the safest pain reliever to take with warfarin (Coumadin, Jantoven). It does not cause bleeding of the lining of the gastrointestinal tract as many other pain relievers do.

However, Hylek et al. found that if a person takes more than 26 regular- strength (325 mg each) or 19 extra-strength (500 mg each) over one week, the International Normalized Ratio (INR) may be raised. This will increase the chance of a person bleeding.

Two articles have added insight as to how this may occur. Lehman hypothesized that various enzymes in the liver may be involved in different patients. These have to do with metabolizing the two forms of warfarin (Coumadin, Jantoven) and acetaminophen. These may come into play with varying conditions such as in older patients, those with atrial fibrillation and congestive heart failure. This theory could account for why some people are affected and some are not.

Whyte et al. reported their observations in a regional toxicology center. They found that a small rise in the INR is common after acetaminophen poisoning without liver injury. This appears to be caused by inhibition of clotting factor VII. This would account for the interaction between acetaminophen and warfarin (Coumadin, Jantoven).

Paracetamol is a generic name for acetaminophen that is commonly used in Europe. Mahe et al conducted a prospective double-blind, cross-over, placebo-controlled study of 11 patients on stable warfarin (Coumadin, Jantoven) therapy. Each received, in random order, two 14-day regimens of paracetamol 4 g per day or placebo, with a 14-day or more wash-out period in between. They found a statistically significant increase in the INR of 1.04 when the participants were taking acetaminophen. They concluded that paracetamol raised the risk of bleeding. I cannot disagree with their findings, but I do disagree with their conclusion. I have checked the results from my clinic on several occasions over the seven plus years that I have been managing warfarin (Coumadin, Jantoven). I do not find that a 1.04 increase in the INR translates into a clinically significant increase in the risk of bleeding. Just because something is statistically significant does not mean that it is clinically significant.

Holbrook et al published the most comprehensive review to date of drug and food interactions with warfarin (Coumadin, Jantoven). They rate this interaction as being highly probable that if a person on warfarin (Coumadin, Jantoven) started taking the amounts of acetaminophen listed above it could cause the INR to increase to the point of requiring an adjustment of the warfarin (Coumadin, Jantoven) dose.

Addendum: Many of you may be familiar with other websites and a story that ran on CNN stating that acetaminophen and warfarin (Coumadin, Jantoven) is a harmful combination. Since I wrote this page, I have had an opportunity to speak with Dr. Hylek. She regretted giving the interview, which was edited to make it appear that she was stating that this combination was harmful.

References:

Hylek EM et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998;279:657-662.

Lehmann DE. Enzymatic shunting: resolving the acetaminophen-warfarin controversy. Pharmacotherapy 2000;20:1464-1468.

Whyte IM et al. Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII. Ther Drug Monit 2000;742-748.

Mahe I et al. Paracetamol: a haemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol. 2005 Mar;59(3):371-4.

Holbrook AM et al. Systematic Overview of warfarin and its drug and food interactions. Arch Intern Med 2005;165:1096-1106.

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Last updated June 14, 2007