Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice Audit.

Area of Science:

• Cardiology
• Clinical Pharmacology

Background:

• Perhexiline, an antianginal agent, is now used for refractory myocardial ischemia, heart failure, hypertrophic cardiomyopathy, and aortic stenosis.
• Long-term perhexiline use carries risks of hepatotoxicity and neuropathy due to drug accumulation and complex pharmacokinetics.
• Regular plasma concentration monitoring is essential for safe long-term perhexiline therapy.

Purpose of the Study:

• To investigate the risk of neurotoxicity and hepatotoxicity during long-term perhexiline therapy in relation to therapeutic drug monitoring intensity.
• To evaluate determinants of mortality in patients receiving long-term perhexiline treatment.

Main Methods:

• A study involving 170 patients treated with perhexiline for a median of 50 months.
• Outcomes and plasma drug concentrations were documented and analyzed.

Main Results:

• Perhexiline was primarily used for myocardial ischemia (88%) and severe systolic heart failure (38%).
• Plasma concentrations were therapeutic in 65% of measurements; toxic levels occurred in 8.8%.
• No hepatotoxicity was observed; 3 patients developed possible peripheral neuropathy. Actuarial 5-year survival was 83% overall and 76.3% in heart failure patients.

Conclusions:

• Therapeutic drug monitoring, despite suboptimal frequency, effectively limits toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity.
• Mortality rates during long-term perhexiline therapy are surprisingly low, especially for patients with concomitant heart failure.