Evaluation of pentamidine tolerability and efficacy between CYP2C19 phenotypes

Pharmacogenomics. 2023 Oct;24(15):821-830. doi: 10.2217/pgs-2023-0093. Epub 2023 Oct 17.

Abstract

Intravenous pentamidine is used for prophylaxis against Pneumocystis jirovecii pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially metabolized by CYP2C19, which is vulnerable to pharmacogenetic variation. This retrospective study evaluated allogeneic hematopoietic stem cell transplant patients who received intravenous pentamidine as P. jirovecii pneumonia prophylaxis. The primary objective was the association between CYP2C19 phenotype and discontinuation of pentamidine due to drug-related side effects based on univariate logistic regression (N = 81). Ten patients (12.3%) discontinued pentamidine because of side effects. There was no difference in discontinuation between phenotype groups (p = 0.18) or discontinuation due to side effects (p = 0.76). Overall, no association was seen between phenotypes and pentamidine-related side effects (p = 0.475). Drug discontinuation rates and P. jirovecii pneumonia infection rates were low.

Keywords: CYP2C19; Pneumocystis jirovecii pneumonia; allogeneic hematopoietic stem cell transplant; hematopoietic stem cell transplant; pentamidine.

MeSH terms

  • Antifungal Agents / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Pentamidine / adverse effects
  • Phenotype
  • Pneumocystis carinii* / genetics
  • Pneumonia, Pneumocystis* / drug therapy
  • Pneumonia, Pneumocystis* / genetics
  • Retrospective Studies

Substances

  • Pentamidine
  • Antifungal Agents
  • Cytochrome P-450 CYP2C19
  • CYP2C19 protein, human