Δ-9-Tetrahydrocannabinol Dose Increase leads to Warfarin Drug Interaction and Elevated INR

Objective Reported is a case of a drug-drug interaction (DDI) involving warfarin and Δ-9-tetrahydrocannabinol (THC) which resulted in a supratherapeutic INR level. The purpose of this case report is to highlight the possibility of a pharmacokinetic DDI between THC and warfarin. Case Summary A 67-year-old Caucasian male, suffering from chronic pain presented to a dispensary in Buffalo, New York for a refill of his medical cannabis (MC). The patient asked to speak with the pharmacist (RPh) and during their discussion the patient stated he had a supratherapeutic INR level of 5.2 measured at home with a self-test device. The patient had no evidence of bleeding and administration of warfarin was held for two days before returning to a normal range. The supratherapeutic level occurred when the patient was self-titrating his dose of THC and scored an 8, "probable", on the Naranjo Adverse Drug Effect Probability Scale. Practice Implications Warfarin and cannabinoids such as THC are both metabolized by Cytochrome P450 (CYP) isozymes present in the liver and gastrointestinal tract. In the case described a dose increase of 7.35 mg THC preceded an INR elevation of 5.2, but did not result in any bleeding. These observations are suggestive of a DDI involving warfarin and THC. Clinicians involved with MC should have adequate knowledge of drugs that act as substrates, inhibitors, and inducers of CYP enzymes, including the major cannabinoids.