cannabinoids can increase INR with coumadin because of CYP inhibition

Patients with LVADs need careful attention to anticoagulation to minimize the competing risks of thrombosis and bleeding. Consideration of potential drug-drug interactions is an important component of that management. Warfarin is metabolized by the CYP450 hepatic enzyme complex. Commercially available warfarin has both an Sand an R-stereoisomer, which complicates evaluations of its interactions, but CYP2C9 is involved in metabolism of both. Cannabinoids, including cannabidiol oil, tetrahydrocannabinol in medical cannabis, and components of smoked or ingested marijuana, are potent inhibitors of CYP2C9 and can increase INR, sometimes dramatically, and contribute to bleeding complications.

Cocaine is metabolized by hepatic esterases and plasma pseudocholinesterase, and amphetamines and opiates are metabolized by hepatic enzymes that do not interact with warfarin metabolism. A drug screen may not be necessary in all patients, but taking a history that inquires about potential drugs of abuse is important, especially in patients on medications with a narrow toxic-to-therapeutic ratio. Certain herbal medications can influence INR as well.

There are a host of prescribed medications that affect warfarin metabolism, many of which are now picked up by electronic health records that detect drug-drug interactions. Drugs that inhibit CYP2C9 and thus increase INR on warfarin include amiodarone, metronidazole, and azole antifungals. Drugs that induce CYP2C9 and thus decrease INR on warfarin include rifampin, phenytoin, and carbamazepine.123

Footnotes

  1. SEEK Questionnaires ↩

  2. Page RL 2nd, Allen LA, Kloner RA, et al; American Heart Association Clinical Pharmacology Committee and Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Lifestyle and Cardiometabolic Health; and Council on Quality of Care and Outcomes Research. Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2020;142(10):e131-e152. PubMed ↩

  3. Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: a systematic review and meta-analysis. Br J Clin Pharmacol. 2021;87(11):4051-4100. PubMed ↩