Therapeutic drug monitoring and pharmacogenomic guided perhexiline therapy in kidney failure requiring haemodialysis: a case study

Background

Ischaemic heart disease is a leading cause of morbidity and mortality in haemodialysis patients, yet conventional therapies are often precluded due to increased perioperative risk and medication contraindications. Perhexiline, an antianginal agent, is contraindicated in renal impairment. Research has suggested therapy in kidney failure may be safe, but these studies excluded patients requiring haemodialysis.

Aim

We describe a novel case of safe and effective long-term perhexiline therapy in a patient requiring haemodialysis, with treatment guided by therapeutic drug monitoring and interpreted in the context of pharmacogenomic screening.

Clinical Details

A male patient, aged 84 years, with an intermediate cytochrome P450 2D6 (CYP2D6) metaboliser phenotype, kidney failure (requiring haemodialysis) and ischaemic heart disease (quintuple coronary artery bypass grafting in 1999 with multiple occluded grafts), and intolerant of conventional antianginal therapy received perhexiline 50 mg, twice daily, for refractory symptomatic ischaemic heart disease for the past three years. [Correction added on 28 April 2025, after first online publication: Some text has been corrected in this section].

Outcomes

Perhexiline and metabolite levels remained within therapeutic range before and after dialysis, and clearance by haemodialysis was negligible. Pharmacogenomic screening and hydroxyperhexiline/perhexiline ratios were consistent with an intermediate CYP2D6 metaboliser phenotype. Therapy in this patient was effective with no adverse events identified.

Conclusion

This case, combined with existing literature, challenges the contraindication of perhexiline in kidney failure. Perhexiline's unique ability to relieve ischaemic symptoms without inducing intolerable blood pressure reduction makes it a therapy of interest in this patient population. Further studies are needed to definitively establish its long-term safety and efficacy in the kidney failure population.