Evaluation of CYP2C19 Genotype‐Guided Voriconazole Prophylaxis After Allogeneic Hematopoietic Cell Transplant

Abstract

There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype‐guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily. Steady‐state trough concentrations were obtained after 5 days, targeting 1.0–5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls (P < 0.001). Zero, 26%, 50%, and 16% of PMs, IMs, NMs, and RMs/UMs were subtherapeutic. Voriconazole success rate was 78% compared with 54% in historical controls (P < 0.001). No patients experienced an invasive fungal infection (IFI). Genotype‐guided dosing resulted in $4,700 estimated per patient savings as compared with simulated controls. CYP2C19 genotype‐guided voriconazole dosing reduced subtherapeutic drug concentrations and effectively prevented IFIs.

PharmVar GeneFocus: CYP2C19

“…Other clinical uses of CYP2C19 genetic testing are to guide prescribing of selective serotonin reuptake inhibitors in the treatment of depression, dosing of proton pump inhibitors for gastroesophageal reflux disease, and dosing of voriconazole for prophylaxis of invasive fungal infection among others. A recent study of CYP2C19 ‐guided voriconazole dosing for antifungal prophylaxis in adult allogeneic hematopoietic cell transplant recipients demonstrated a decrease in the percent of patients with subtherapeutic concentrations and improved treatment success rates with the genotype‐guided approach compared with historical controls, with an estimated cost savings of $4,700 per patient 23 …”

“…A recent study of CYP2C19-guided voriconazole dosing for antifungal prophylaxis in adult allogeneic hematopoietic cell transplant recipients demonstrated a decrease in the percent of patients with subtherapeutic concentrations and improved treatment success rates with the genotype-guided approach compared with historical controls, with an estimated cost savings of $4,700 per patient. 23 Given the clinical significance of CYP2C19 genotype information, it is imperative that test information is accurate and that providers understand the limitations of a genotype test. Recommendations for clinical CYP2C19 genotyping allele selection have been published 24 and test options are discussed in detail elsewhere.…”

Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review

“…Two studies examined the effect of prospective CYP2C19guided voriconazole dose selection (Table 4). 72,73 In the prospective study by Hicks et al, 72 263 acute myeloid leukemia patients were CYP2C19-genotyped before receiving prophylactic oral voriconazole. 72 RMs were recommended 300 mg twice daily, URMs were recommended to avoid voriconazole, and all others received a standard twice-daily 200-mg dose.…”

A Case Report of Maxillary Aspergillosis with Unusual Clinical and Imaging Presentations

“…14 Adjusting the variconazole dose can be challenging, especially in patients with compromised liver function and patients with hematopoietic cell transplant. 15,16 Fortunately, in this case report, the patient was free of any predisposing factors affecting the immune system.…”