This episode dives into a 2026 case report revealing a surprising drug interaction: ketamine, used for pain management, induced the liver to accelerate the breakdown of critical immunosuppressant medications in a heart transplant recipient. Transplant patients rely on a delicate balance, where drugs like tacrolimus and sirolimus prevent organ rejection. However, these drugs are metabolized by specific liver enzymes (CYP3A4), making them vulnerable to interactions.

In this case, a patient receiving ketamine for post-surgical pain experienced a dramatic drop in immunosuppressant levels, placing his transplanted heart at risk. Doctors responded by drastically increasing the doses, but the drug concentrations barely budged. The ketamine was essentially "teaching" the liver to clear the drugs faster, a phenomenon known as enzyme induction. The peak effect occurred a week after ketamine was started, followed by a slow recovery over three weeks.

The episode emphasizes the importance of vigilant monitoring when ketamine is used in patients on narrow therapeutic range medications, and that monitoring should continue for three weeks after ketamine is discontinued to catch any potential rebound effects.

Reference:

Stojanova, J., Murnion, B., Burrows, F., Carlos, L., Mizuno, T., Nadai, T., Helsby, N., Muthiah, K., & Day, R. (2026). Continuous Subcutaneous Ketamine Infusion May Induce Tacrolimus and Sirolimus Clearance: A Case Report. *Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy*, *46*(e70150). https://doi.org/10.1002/phar.70150