Sotorasib associated with tacrolimus and everolimus: A significant drug interaction in lung transplant patients

Transpl Immunol. 2022 Oct:74:101678. doi: 10.1016/j.trim.2022.101678. Epub 2022 Jul 25.

Abstract

The management of immunosuppressors in solid organ transplantation requires pharmacological therapeutic monitoring with regular adaptation of the dosage to the residual level. An obvious cause of these fluctuations is drug interactions, particularly for mTOR inhibitors and anti-calcineurin drugs, which are highly metabolized by cytochromes P450. A 72-year-old lung transplanted man, treated by tacrolimus and everolimus in the long term, had his residual immunosuppressor levels unbalanced by the introduction of sotorasib, which is used for metastatic pulmonary adenocarcinoma. This imbalance is explained by the fact that sotorasib is an inducer of CYP3A4 and an inhibitor of PGP, but the strength of the interaction has never been studied. This will have required a threefold increase in dosages and weekly monitoring before satisfactory residual levels were achieved.

Keywords: Anti-rejection therapy; Enzyme induction; Lung adenocarcinoma; Solid organ transplantation; Sotorasib.

MeSH terms

  • Aged
  • Calcineurin Inhibitors
  • Drug Interactions
  • Everolimus / therapeutic use
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation*
  • Male
  • Piperazines
  • Pyridines
  • Pyrimidines
  • Tacrolimus* / therapeutic use

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Piperazines
  • Pyridines
  • Pyrimidines
  • sotorasib
  • Everolimus
  • Tacrolimus