In this episode, I’ll discuss a case report of the effects of ketamine on the clearance of tacrolimus and sirolimus.
Beyond ex vivo models showing that ketamine induces the clearance of CYP450 substrates, little is known about its effects in patients. A group of authors present in Pharmacotherapy a case report on the effects of a continuous ketamine infusion in a patient who was also a heart transplant recipient receiving tacrolimus and sirolimus.
The case is that of a 55 year-old male who was given ketamine 5 to 10 mg / hr via continuous subcutaneous infusion for the treatment of pain after lower limb thrombectomy. The authors monitored the patient’s tacrolimus and sirolimus concentrations throughout hospitalization and rehabilitation.
11 days after ketamine was initiated, the tacrolimus and sirolimus levels were both noted to be about 3 ng/mL which was far below the target combined concentration of 10 ng/mL.
The patient’s dose of tacrolimus was increased from 4 to 7 mg, and sirolimus from 1 to 5 mg daily.
Tacrolimus concentrations didn’t budge despite the dose increase, and the sirolimus concentration only doubled despite the 5-fold dose increase.
After ketamine discontinuation, the patient’s tacrolimus and sirolimus concentrations steadily increased over 3 weeks. The authors noted the onset and offset is consistent with enzyme induction and subsequent recovery.
The authors concluded:
This case provides preliminary evidence of potential interaction between ketamine and CYP3A4-metabolized immunosuppressants. Clinicians should consider increased therapeutic drug monitoring when using ketamine with narrow therapeutic range medications, continuing approximately 3 weeks post-discontinuation.
With the increased push for ketamine infusions as analgesia instead of opioids, pharmacists will need to watch out for clinically significant interactions such as those described in this case.
To access my free download area with 20 different resources to help you in your practice, go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Leave a Reply