Electrocardiogram abnormalities in patients with acne undergoing isotretinoin therapy: a focused review<sup/>

Islam, Afra Wasama; Motdhare, Prarthana; Mohan, Shreya; Bejoy, Swapna; Wilkhoo, Harsahaj Singh

doi:10.1016/j.abd.2026.501304

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Review • An. Bras. Dermatol. 101 (2) • 2026 • https://doi.org/10.1016/j.abd.2026.501304 linkcopy

Electrocardiogram abnormalities in patients with acne undergoing isotretinoin therapy: a focused review^☆

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Isotretinoin is an extremely successful treatment for acne, widely prescribed for moderate to severe cases unresponsive to conventional therapy that is commonly used in dermatology. While its systemic side effects, particularly those related to hepatic and lipid metabolism, are extensively documented, its impact on cardiac electrophysiology is little understood. Metabolic abnormalities are frequent, with hypertriglyceridemia occurring in up to 44% of patients, elevated total cholesterol in 30%, and transient liver enzyme elevation in approximately 10%-11%. This focused review summarizes the existing research on electrocardiographic (ECG) alterations associated with isotretinoin medication. Reported cardiac abnormalities are rare, with isolated case reports and small studies describing transient arrhythmias in fewer than 1%-2% of users, including premature ventricular contractions (PVCs), atrial tachycardia, and, in exceptionally rare instances, cardiomyopathy < 0.01%. Mechanistic ideas suggest changes in human ether-a-go-go-related gene (hERG) potassium channels, dyslipidemia-induced atherosclerosis, electrolyte imbalances, and sympathetic overactivity. However, large population-based studies have not found a significant increase in major cardiovascular events. Most ECG abnormalities, when noted, appear to be reversible with discontinuing isotretinoin. This review is unique in that it focuses on isotretinoin from both dermatological and cardiac viewpoints. It identifies important shortcomings in standardized ECG monitoring procedures and underscores the scarcity of large, prospective, controlled trials. Future research should focus on longitudinal, multicenter trials using serial ECG evaluations to better define risk profiles and guide clinical monitoring. Understanding infrequent but potentially serious cardiac effects is critical for improving isotretinoin's safety profile and guiding evidence-based therapy.

Keywords
Acne vulgaris; Cardiac electrophysiology; Electrocardiography; Isotretinoin

Category	Details
Metabolism	• Lipophilic, distributed in adipose tissue
	• ∼99.9% bound to plasma proteins (mainly albumin)
	• Bioavailability increases with high-fat meals
	• Metabolized in the liver by CYP2C8, CYP2C9, CYP3A4, CYP2B6
	• Active and inactive metabolites: 4-oxo-isotretinoin, retinoic acid, 4-oxo-retinoic acid
	• Excretion: urine and feces after conjugation
Most common adverse effects	• Cheilitis (up to 94%)
	• Hypertriglyceridemia (∼44%)
	• Increased total cholesterol (∼30%)
	• ↑ LDL, ↓ HDL
	• Transient liver transaminase elevations (∼11%)
Less reported / Rare adverse effects	• Cardiac: sinus tachycardia, atrial tachycardia, premature ventricular contractions (PVCs), right bundle branch block, pericardial effusion, dilated cardiomyopathy, renal infarction (very rare)
	• Electrolytes: hypokalemia, ↑ phosphorus, ↑ magnesium, ↑ zinc
	• Autonomic changes: transient ↑ sympathetic activity (SSR findings)

Case	Event	Dose	Time of Onset	Outcome	Reversibility
16-year-old boy (Hasdemir et al., 2005)¹⁵	Atrial tachycardia	Not specified	During therapy (≈3-months)	Symptom resolution after discontinuation	Yes, reversible

33-year-old woman (Alan et al., 2016) ⁵	Premature ventricular contractions (PVCs)	Not specified	∼1-month into therapy	Arrhythmia resolved after drug withdrawal	Yes, reversible

18-year-old male (Pepe et al., 2023) ¹⁴	Dilated cardiomyopathy + renal infarction + non-sustained VT	Not specified	After 5-months of isotretinoin	Severe cardiac dysfunction requiring discontinuation	Not fully reversible (serious outcome)

Pediatric case (Kiliç et al., 2009) ²⁷	Premature ventricular contractions (PVCs)	Not specified	During isotretinoin treatment	Resolved after discontinuation	Yes, reversible

General reports (multiple cases, summarized)	Sinus tachycardia, right bundle branch block, pericardial effusion	Variable	During treatment	Generally transient and non-lethal	Typically, reversible

ECG Parameter	Clinical Relevance	Findings in Isotretinoin Studies	Implication
QT Interval / QTc	Prolongation can predispose to torsades de pointes and sudden cardiac death	No significant changes in QT interval or QT dispersion over 6 months of isotretinoin therapy.	Suggests isotretinoin does not prolong QT interval in most patients

Heart Rate Variability (HRV)	Marker of autonomic nervous system balance; reduced HRV indicates sympathetic dominance	SSR changes suggest transient increase in sympathetic activity; no ECG evidence of HRV changes	Possible transient autonomic modulation without clinically significant impact

T-Wave Morphology	Abnormalities may indicate repolarization issues and risk for arrhythmia	No consistent evidence of T-wave abnormalities in larger studies; isolated reports of arrhythmias exist	No established correlation with T-wave changes

Bradyarrhythmias	Slowed heart rhythm; can be drug-induced or related to conduction issues	No documented cases of isotretinoin-induced bradyarrhythmia	Not a common concern

Premature Ventricular Contractions (PVCs)	Can be benign or a precursor to serious arrhythmia depending on frequency and patient context	Documented in case reports; generally resolved after discontinuation of isotretinoin	Rare
Premature Ventricular Contractions (PVCs)			Reversible, may indicate individual susceptibility

Risk Factor	Description	Clinical Consideration / Monitoring
High Isotretinoin Dose	Daily dose ≥ 1 mg/kg/day, or cumulative dose > 120-150 mg/kg (upper end of standard range). Higher plasma levels are associated with more frequent lab abnormalities and theoretical cardiac risk.	• Baseline ECG and labs (lipids, LFTs, electrolytes).
		• Repeat ECG at 1-3 months if high-dose regimen.
		• Monthly lipid and LFT monitoring for first 2-3 months, then q2-3 months.
Pre-existing Cardiac Conditions	History of arrhythmia, congenital conduction defects, cardiomyopathy, structural heart disease.	• Baseline cardiology consult and ECG.
		• Repeat ECG at 1 and 3 months, then q3-6 months.
		• Closer follow-up if symptomatic.
Electrolyte Imbalance	Hypokalemia, hypomagnesemia, hypocalcemia, or trace element disturbances (Zn, P). These may potentiate arrhythmias.	• Correct electrolyte disturbances before starting.
Electrolyte Imbalance		• Monitor electrolytes at baseline and periodically (every 2-3 months, or sooner if symptomatic).
Concomitant Medications	Especially QT-prolonging drugs (e.g., macrolides, fluoroquinolones, antipsychotics, antiarrhythmics).	• Review drug history.
		• Avoid combining with other QT-prolonging agents when possible.
		• ECG monitoring at baseline and if new QT-prolonging drug is added.
Age and Autonomic Tone	Younger patients may have higher vagal tone and autonomic variability; adolescents/young adults form the bulk of isotretinoin users.	• Baseline ECG.
		• Educate patients on palpitations, syncope, chest discomfort.
		• No additional routine ECG unless symptomatic or other risk factors present.

Recommendation	Rationale	Implementation
Baseline ECG before starting isotretinoin	To detect pre-existing abnormalities	Routine screening
Monitor HR and QTc in high-risk patients	Identify clinically significant changes	Periodic ECG checks
Electrolyte panel monitoring	Avoid confounding cardiac effects	Especially if symptomatic
Patient education on cardiac symptoms	Prompt detection of palpitations/syncope	During consent/counseling

Drug/Class	Common non-cardiac adverse effects	Cardiac/Cardiovascular adverse events	Risk Magnitude & Reversibility
Isotretinoin	Cheilitis (≈94%), xerosis, dry eyes, arthralgia, transient ↑LFTs, ↑TG/LDL, ↓HDL	Rare: atrial tachycardia, PVCs, transient RBBB, pericardial effusion, dilated cardiomyopathy (isolated). Dyslipidemia may increase atherosclerotic risk long-term.	Population studies: no increase in major CV events. Most arrhythmias reversible after discontinuation.
Tetracyclines (doxycycline, minocycline)	GI upset, photosensitivity (doxy), vestibular symptoms (mino), hypersensitivity/ DRESS (mino)	Generally, QT-neutral (doxycycline not QT-prolonging). Very rare: minocycline-induced eosinophilic myocarditis within hypersensitivity syndromes.	No population-level signal for CV events. Myocarditis rare, improves after cessation + immunomodulation.
Combined Oral Contraceptives (COCs)	Nausea, breast tenderness, breakthrough bleeding, headache	Venous thromboembolism (VTE): 2-3× baseline risk. ↑ risk of arterial events (MI, stroke) in smokers > 35, or with migraine with aura. No QT/ECG effect.	Absolute VTE risk: ∼7-10/10,000 women-years vs. 4/10,000 non-users. Risk falls rapidly after discontinuation.
Spironolactone (female acne)	Menstrual irregularities, breast tenderness, fatigue, diuresis	Hyperkalemia (rare in healthy young women; higher in CKD/with RAAS blockers). No intrinsic proarrhythmic signal; some evidence of QTc shortening in cardiac cohorts.	Low risk in healthy women. Lab abnormalities usually within weeks, reversible with dose adjustment or cessation.

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Electrocardiogram abnormalities in patients with acne undergoing isotretinoin therapy: a focused review☆

Electrocardiogram abnormalities in patients with acne undergoing isotretinoin therapy: a focused review^☆