Isotretinoin Does Not Prolong QT Intervals and QT Dispersion in Patients With Severe Acne: A Surprising Finding for a Drug With Numerous Side Effects

July 2011 | Volume 10 | Issue 7 | Original Article | 710 | Copyright © 2011

Abstract

Background: Isotretinoin is a widely prescribed drug for the treatment of severe acne. Several adverse cardiac effects due to isotretinoin have been previously reported. However, no data exist on the effects of isotretinoin therapy on QT intervals.
Objective: To investigate the effects of isotretinoin therapy on QT intervals and QT dispersion, and also to see if it is related to serum lipids, homocysteine and lipoprotein (a) or not.
Methods: Forty-five patients with severe acne (mean age 21±6 years, range 14-38 years; 26 female) were included in the study. Twelve-lead surface electrocardiograms (ECGs) were acquired at three stages: before therapy and at the ends of the first and sixth months of 0.8 mg/kg/day of isotretinoin therapy. Serum levels of triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, homocysteine and lipoprotein (a) were also measured at the day of ECG recordings. Minimum and maximum QT intervals were measured and QT dispersion was calculated.
Results: Mean heart rates were similar throughout the isotretinoin therapy. Serum levels of lipids, homocysteine and lipoprotein (a) all increased significantly at the end of the first month and remained significantly elevated at the end of sixth month (P<0.05 for both stages). QT intervals and QT dispersion did not differ significantly throughout the six months of isotretinoin therapy (P>0.05).
Conclusions: In patients with severe acne, six months of 0.8 mg/kg/day of isotretinoin therapy neither prolongs QT interval, nor increases QT dispersion. This effect is not related to blood lipids, homocysteine or lipoprotein (a) levels. Our findings indicate that from the point of polymorphic ventricular tachycardia risk, 0.8 mg/kg/day of isotretinoin therapy is a safe choice in acne treatment.

J Drugs Dermatol. 2011;10(7):710-714.

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INTRODUCTION

Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A derivative which is commonly prescribed in dermatologic diseases, especially in patients with severe acne. Although the exact mechanism of action of isotretinoin is not known, it is the most effective therapy for acne. The drug is also well-known for its numerous adverse effects.1,2

Several adverse cardiac effects related to isotretinoin use, including atrial tachycardias, premature ventricular contractions and right bundle branch block (RBBB) with sinus tachycardia have been reported.3-6 However, to the best of our knowledge, the effects of isotretinoin on QT intervals and QT dispersion (QTd) have not been investigated before.

It is well-known that prolonged QT intervals and increased QT dispersion may predispose to potentially fatal ventricular arrhythmias such as polymorphic ventricular tachycardia (torsades de pointes). Drug usage is one of the reasons for QT interval prolongation. Several non-cardiac drugs, including clarithromycine, erythromycin, haloperidol, cisapride, chloroquine and mesoridazine have been reported to prolong the QT interval.7 The QT prolonging effect of a drug becomes even more important when multiple drugs need to be combined.

QTd is defined as the interlead variability of the QT interval and is assumed to reflect regional variations in ventricular repolar-

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