Chlortalidone

ATC code

C03BA04

Therapeutic class

Thiazide-like diuretic · Sulfonamide, monocomponent

Forms

oral tablet

Brand names

Higrotona (ES) · Thalitone (US)

Overall confidence

high

Regulatory sources consulted

Approved indications

Essential hypertension.
Edema of cardiac, renal, or hepatic origin.
Stable chronic heart failure (functional classes II and III).
Nephrogenic diabetes insipidus.

Contraindications

Absolute

Hypersensitivity to chlortalidone or other sulfonamides.
Severe renal impairment (creatinine clearance < 30 ml/min).
Severe liver disease or hepatic encephalopathy.
Refractory hypokalemia or hyponatremia.

Clinical warnings

Major warning · Electrolyte imbalance: May cause hypokalemia, hyponatremia, and hypomagnesemia. Periodic monitoring of serum electrolytes is required. — AEMPS SPC
Hyperuricemia: May increase uric acid levels and precipitate gout attacks in susceptible patients. — AEMPS SPC

Drug interactions

HighLithiumN05AN01
Mechanism: Decreased renal clearance of lithium, leading to increased serum levels and risk of lithium toxicity.
Recommendation: Avoid concomitant use. If necessary, monitor lithium levels closely and adjust the dose.
ANSM RCPAEMPS SPC

Adverse events

Common (≥1%)

hypokalemia · hyperuricemia · hyperlipidemia · hyponatremia · dizziness · postural hypotension

Rare but serious

pancreatitis · arrhythmias · thrombocytopenia · interstitial nephritis · idiosyncratic pulmonary edema

Pregnancy and lactation

FDA category: Not Recommended

Generally not recommended during pregnancy and lactation. It crosses the placental barrier and is excreted in breast milk. May cause electrolyte imbalances in the fetus/newborn.

Recent literature (PubMed)

Comparison of the Effectiveness and Safety of Chlorthalidone and Hydrochlorothiazide in Patients With Hypertension: A Meta-Analysis.
Khenhrani RR, et al. · Cureus · 2023 · Relevance 5/5
Meta-análisis de 8 estudios que concluye que la clortalidona es superior a la hidroclorotiazida (HCTZ) en la reducción de la presión arterial sistólica y diastólica. No se encontraron diferencias significativas en el riesgo de infarto de miocardio, ictus o mortalidad por todas las causas. Sin embargo, la tasa de hipopotasemia fue mayor con clortalidona.
Prevention of Heart Failure in Hypertension-the Role of Coronary Heart Disease Events Treated With Versus Without Revascularization: The ALLHAT Study.
Chen V, et al. · Am J Cardiol · 2024 · Relevance 5/5
Análisis de mediación causal del ensayo ALLHAT que sugiere que los antihipertensivos como la clortalidona previenen la insuficiencia cardíaca principalmente a través de vías distintas a la simple prevención de eventos de enfermedad coronaria (EC). La EC modera pero no media el efecto protector sobre la insuficiencia cardíaca.
Efficacy and Safety of Chlortalidone and Hydrochlorothiazide in Prevention of Cardiovascular Diseases.
Song XN, et al. · Rev Cardiovasc Med · 2024 · Relevance 4/5
Meta-análisis que compara clortalidona vs. hidroclorotiazida (HCTZ). No encontró diferencias claras en los resultados cardiovasculares (infarto de miocardio, insuficiencia cardíaca, eventos CV, muerte), a pesar de la percepción de un mayor riesgo de efectos adversos con clortalidona. Sugiere que la elección puede basarse en otros factores.