immunosuppressants drug action

 Q: All of the following drugs may increase the serum concentrations of immunosuppressants EXCEPT? 

A) Amiodarone 

B) Fluconazole

C) Phenytoin 

D) Azithromycin 

E) Diltiazem

Answer: C

The objective of this question is to enhance the fragile serum levels of immunosuppressants in relatively sick patients in ICU. Most of the commonly used drugs in ICU have some kind of interaction with immunosuppressants i.e., cyclosporine, tacrolimus, sirolimus, or everolimus. Drug interactions may either increase the serum level of these immunosuppressants or decrease the level. Some drugs may just have the additive effect, and some may just cause hyperkalemia. This is beyond the scope here to list all such drugs. It can be very tricky as macrolide antibiotics increase the serum level of immunosuppressant but nafcillin decreases the level! Most of the interactions occur via CYP3A metabolism and/or P-glycoprotein drug efflux pump. 

All the drugs in the above question except choice C increase the serum levels of immunosuppressant. In fact, phenytoin decreases the tacrolimus level and has been tried as an antidot in tacrolimus toxicity.

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References:

1. Katalin Monostory (July 25th 2018). Metabolic Drug Interactions with Immunosuppressants, Organ Donation and Transplantation - Current Status and Future Challenges, Georgios Tsoulfas, IntechOpen, DOI: 10.5772/intechopen.74524. Available from: https://www.intechopen.com/books/organ-donation-and-transplantation-current-status-and-future-challenges/metabolic-drug-interactions-with-immunosuppressants (last accessed March 15, 2021)

2. Jantz AS, Patel SJ, Suki WN, Knight RJ, Bhimaraj A, Gaber AO. Treatment of acute tacrolimus toxicity with phenytoin in solid organ transplant recipients. Case Rep Transplant. 2013;2013:375263. doi:10.1155/2013/375263