Chlortalidone

Long-acting thiazide-like diuretic

ATC code: C03BA04

Brand names: Thalitone, Tenoretic

Updated 24 Sep 2026 · Methodology

Indications

Hypertension

First line

Chlorthalidone is a thiazide-like diuretic. The AEMPS Higrotona label puts arterial hypertension first among its indications, as monotherapy or in combination. The 2024 guideline keeps thiazide-like diuretics in the first line beside ACE inhibitors, sartans and calcium channel blockers, and within the group it favours chlorthalidone and indapamide over hydrochlorothiazide: the long half-life covers night-time blood pressure in a way a short-acting drug does not. Working doses in hypertension are low, 12.5–25 mg daily, and pushing the dose adds more adverse effects than millimetres of mercury. Potassium and sodium are checked 1–2 weeks after starting, then every 4–6 months, and more often in older people, because hyponatraemia unfolds on day 5-14.

Sources

ICD-10: I10 · ICD-11: BA00

Resistant arterial hypertension

Second line

In resistant hypertension, swapping hydrochlorothiazide for chlorthalidone is one of the first moves, because a short-acting diuretic leaves the night and early morning uncovered. Chronic kidney disease raises a separate question: thiazides were long held to stop working below 30 ml/min of filtration. The CLICK trial (N Engl J Med 2021) tested that in 160 patients with stage 4 disease and poorly controlled blood pressure: chlorthalidone 12.5–50 mg over 12 weeks lowered 24-hour systolic pressure by about 11 mmHg more than placebo and reduced albuminuria. The price showed up in the same numbers: hypokalaemia, a reversible rise in creatinine, episodes of dizziness. The practical conclusion is that the drug works at reduced filtration but calls for electrolytes and creatinine every 2–4 weeks during titration.

Sources

ICD-10: I10 · ICD-11: BA00

Symptomatic edema

Second line

The AEMPS Higrotona label keeps a narrow list of oedematous states: oedema from renal failure and ascites from hepatic cirrhosis in stable patients under medical supervision. The list is that narrow rather than oedema in general, because a thiazide-like diuretic is weaker than a loop agent and falls short once fluid retention is marked. In ascites the standard pair is spironolactone with furosemide, and chlorthalidone stays in reserve. Electrolyte monitoring here is tighter than in hypertension: the label asks for particular attention to sodium and potassium in older people, in ascites and in nephrotic syndrome, and in nephrotic syndrome it allows the drug only in patients with normal potassium and no signs of volume depletion. Below 30 ml/min of filtration the label lists chlorthalidone as contraindicated.

Sources

AEMPS: Ficha técnica Higrotona 50 mg comprimidos (2025)

ICD-10: R60.9 · ICD-11: MG29.Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Kidney stone prevention

Not recommended

Thiazides reduce urinary calcium excretion, and for half a century that supported a conclusion: they must protect against recurrent calcium stones. The NOSTONE trial (N Engl J Med 2023) tested the conclusion head-on: 416 people with recurrent calcium stones took hydrochlorothiazide 12.5, 25 or 50 mg or placebo and were followed for about three years. Recurrence reached 59% on placebo and 59%, 56% and 49% across the dose groups, and the difference did not hold statistically. Chlorthalidone has no stone trial of its own at all, and the AEMPS Higrotona label carries no such indication. The adverse effects meanwhile are real: hypokalaemia, hyponatraemia, gout, new-onset diabetes. If chlorthalidone was prescribed purely to prevent stones, consider seeking a second opinion.

Sources

ICD-10: N20.0 · ICD-11: GB70.0

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Chlorthalidone blocks the NCC sodium-chloride cotransporter in the distal convoluted tubule. Sodium and chloride leave in the urine, water follows, and circulating volume falls. After several weeks the diuretic effect fades while blood pressure stays down through reduced peripheral resistance. Kinetics set it apart from hydrochlorothiazide: a half-life of 40–60 hours against 6–15 hours, accumulation in red cells and round-the-clock action. The sodium delivered to the collecting ducts is exchanged for potassium, and potassium leaves, which is where the dose-dependent hypokalaemia comes from. Per the AEMPS Higrotona label, 25–50 mg a day lowers serum potassium by about 0.5 mmol/L on average. Urinary calcium falls instead, while serum uric acid rises.

Safety

Contraindications

Hypersensitivity to chlorthalidone or to any excipient
Anuria
Severe renal impairment (creatinine clearance below 30 ml/min)
Severe hepatic impairment
Refractory hypokalaemia and states with large potassium losses
Hyponatraemia, hypercalcaemia
Symptomatic hyperuricaemia: history of gout or urate stones
Hypertension during pregnancy
Addison disease

Serious adverse effects

Severe hyponatraemia with confusion, seizures and falls
Ventricular arrhythmia on the back of hypokalaemia, especially next to QT-prolonging drugs and digoxin
Lithium toxicity on co-administration: the diuretic lowers renal lithium clearance
Acute gout attack
Hepatic coma in patients with cirrhosis after an abrupt electrolyte shift

Common adverse effects

Hypokalaemia: weakness, muscle cramps, palpitations
Hyponatraemia, especially in the first two weeks and in older people
Hyperuricaemia
Dizziness and orthostatic hypotension
Impaired glucose tolerance

Pregnancy: can you take Chlortalidone?

The AEMPS Higrotona label lists hypertension during pregnancy among the contraindications. Thiazide-like diuretics reduce maternal plasma volume and placental flow, and thrombocytopenia, jaundice and electrolyte shifts have been described in the newborn. Blood pressure in pregnancy is lowered with methyldopa, labetalol or extended-release nifedipine.

Breastfeeding: can you take Chlortalidone?

Chlorthalidone passes into breast milk and at higher doses suppresses milk production. A breastfeeding mother who needs blood pressure treatment is given a different drug, and when a diuretic is still required the infant is watched for lethargy and poor weight gain.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Label mentions48 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorLithium
«Litio: La administración concomitante de clortalidona y litio conduce a un aumento del efecto cardiotóxico y neurotóxico del litio debido a la reducción de la excreción de litio. Si a pesar de ello…»
AEMPS, section 4.5 · Open on CIMA
ModerateAcetylsalicylic acid
«Medicamentos antiinflamatorios no esteroideos (por ejemplo, indometacina, ácido acetilsalicílico), incluidos los inhibidores de la COX-2, salicilatos.»
AEMPS, section 4.5 · Open on CIMA
ModerateAINEclass named in the label
«Medicamentos antiinflamatorios no esteroideos (por ejemplo, indometacina, ácido acetilsalicílico), incluidos los inhibidores de la COX-2, salicilatos.»
AEMPS, section 4.5 · Open on CIMA
ModerateAllopurinol
«Alopurinol: Clortalidona puede aumentar las reacciones de hipersensibilidad al alopurinol.»
AEMPS, section 4.5 · Open on CIMA
ModerateAmiodarone
«Sustancias que pueden desencadenar torsades de pointes: - antiarrítmicos de clase III (por ejemplo, amiodarona, sotalol)»
AEMPS, section 4.5 · Open on CIMA
ModerateAmisulpride
«Sustancias que pueden desencadenar torsades de pointes: - ciertos antipsicóticos: fenotiazinas (por ejemplo, clorpromazina, ciamemazina, levomepromazina, tioridazina, trifluoperazina), benzamidas…»
AEMPS, section 4.5 · Open on CIMA
ModerateAmphotericin B
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Diuréticos kaliuréticos (p. ej., furosemida), glucocorticoides, ACTH, carbenoxolona, penicilina G, salicilatos, laxantes estimulantes…»
AEMPS, section 4.5 · Open on CIMA
Moderateantagonistas del calcioclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Otros diuréticos, otros medicamentos antihipertensivos (p. ej., betabloqueantes, antagonistas del calcio, inhibidores de la ECA…»
AEMPS, section 4.5 · Open on CIMA
Moderateantiarrítmicosclass named in the label
«Sustancias que pueden desencadenar torsades de pointes: - antiarrítmicos de clase Ia (por ejemplo, quinidina, hidroquinidina, disopiramida)»
AEMPS, section 4.5 · Open on CIMA
Moderateantidepresivos tricíclicosclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Otros diuréticos, otros medicamentos antihipertensivos (p. ej., betabloqueantes, antagonistas del calcio, inhibidores de la ECA…»
AEMPS, section 4.5 · Open on CIMA
Moderateantidiabéticosclass named in the label
«También son posibles interacciones con las siguientes combinaciones: El efecto de estos medicamentos puede verse debilitado por el uso concomitante de clortalidona. Puede ser necesario ajustar la…»
AEMPS, section 4.5 · Open on CIMA
Moderateantidiabéticos oralesclass named in the label
«También son posibles interacciones con las siguientes combinaciones: Insulina, antidiabéticos orales, medicamentos reductores del ácido úrico, simpaticomiméticos (norepinefrina epinefrina).»
AEMPS, section 4.5 · Open on CIMA
Moderateantineoplásicosclass named in the label
«También son posibles interacciones con las siguientes combinaciones: Medicamentos citostáticos (por ejemplo, ciclofosfamida, fluorouracilo, metotrexato)»
AEMPS, section 4.5 · Open on CIMA
Moderateantipsicóticosclass named in the label
«Sustancias que pueden desencadenar torsades de pointes: - ciertos antipsicóticos: fenotiazinas (por ejemplo, clorpromazina, ciamemazina, levomepromazina, tioridazina, trifluoperazina), benzamidas…»
AEMPS, section 4.5 · Open on CIMA
Moderatebarbitúricosclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Otros diuréticos, otros medicamentos antihipertensivos (p. ej., betabloqueantes, antagonistas del calcio, inhibidores de la ECA…»
AEMPS, section 4.5 · Open on CIMA
Moderatebetabloqueantesclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Otros diuréticos, otros medicamentos antihipertensivos (p. ej., betabloqueantes, antagonistas del calcio, inhibidores de la ECA…»
AEMPS, section 4.5 · Open on CIMA
Moderatebloqueantes neuromuscularesclass named in the label
«También son posibles interacciones con las siguientes combinaciones: Relajantes musculares no despolarizantes (tipo curare) (por ejemplo, cloruro de tubocurarina)»
AEMPS, section 4.5 · Open on CIMA
ModerateCaptopril
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): La toma de inhibidores de la ECA (por ejemplo, captopril, enalapril) durante el tratamiento clortalidona crea el riesgo de una caída grave…»
AEMPS, section 4.5 · Open on CIMA
ModerateChlorpromazine
«Sustancias que pueden desencadenar torsades de pointes: - ciertos antipsicóticos: fenotiazinas (por ejemplo, clorpromazina, ciamemazina, levomepromazina, tioridazina, trifluoperazina), benzamidas…»
AEMPS, section 4.5 · Open on CIMA
ModerateCiclosporin
«Ciclosporina: La administración concomitante de ciclosporina puede aumentar el riesgo de hiperuricemia y complicaciones similares a la gota.»
AEMPS, section 4.5 · Open on CIMA
ModerateCisapride
«Sustancias que pueden desencadenar torsades de pointes: - otros: bepridil, cisaprida, difemanil, eritromicina i.v., halofantrina, mizolastina, pentamidina, esparfloxacino, moxifloxacino, vincamina…»
AEMPS, section 4.5 · Open on CIMA
Moderatecorticosteroidesclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Diuréticos kaliuréticos (p. ej., furosemida), glucocorticoides, ACTH, carbenoxolona, penicilina G, salicilatos, laxantes estimulantes…»
AEMPS, section 4.5 · Open on CIMA
Moderatedigitálicosclass named in the label
«El uso concomitante de clortalidona y estos medicamentos puede producir desequilibrios electrolíticos, especialmente un aumento de la depleción de potasio. Esto debe tenerse en cuenta en particular…»
AEMPS, section 4.5 · Open on CIMA
ModerateDisopyramide
«Sustancias que pueden desencadenar torsades de pointes: - antiarrítmicos de clase Ia (por ejemplo, quinidina, hidroquinidina, disopiramida)»
AEMPS, section 4.5 · Open on CIMA
Moderatediuréticos ahorradores de potasioclass named in the label
«Electrolitos: Si resulta necesario, la clortalidona puede combinarse con suplementos orales de potasio o diuréticos ahorradores de potasio (por ejemplo, triamtereno). En caso de terapia combinada…»
AEMPS, section 4.4 · Open on CIMA
Moderatediuréticos del asaclass named in the label
«La administración simultánea de clortalidona y un diurético de asa tiene un efecto sinérgico sobre la diuresis y se requiere una estrecha vigilancia de la función renal, electrolitos y signos de…»
AEMPS, section 4.5 · Open on CIMA
ModerateDroperidol
«Sustancias que pueden desencadenar torsades de pointes: - ciertos antipsicóticos: fenotiazinas (por ejemplo, clorpromazina, ciamemazina, levomepromazina, tioridazina, trifluoperazina), benzamidas…»
AEMPS, section 4.5 · Open on CIMA
ModerateEnalapril
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): La toma de inhibidores de la ECA (por ejemplo, captopril, enalapril) durante el tratamiento clortalidona crea el riesgo de una caída grave…»
AEMPS, section 4.5 · Open on CIMA
ModerateErythromycin
«Sustancias que pueden desencadenar torsades de pointes: - otros: bepridil, cisaprida, difemanil, eritromicina i.v., halofantrina, mizolastina, pentamidina, esparfloxacino, moxifloxacino, vincamina…»
AEMPS, section 4.5 · Open on CIMA
ModerateFluorouracil
«También son posibles interacciones con las siguientes combinaciones: Medicamentos citostáticos (por ejemplo, ciclofosfamida, fluorouracilo, metotrexato)»
AEMPS, section 4.5 · Open on CIMA
ModerateFurosemide
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Diuréticos kaliuréticos (p. ej., furosemida), glucocorticoides, ACTH, carbenoxolona, penicilina G, salicilatos, laxantes estimulantes…»
AEMPS, section 4.5 · Open on CIMA
ModerateHaloperidol
«Sustancias que pueden desencadenar torsades de pointes: - ciertos antipsicóticos: fenotiazinas (por ejemplo, clorpromazina, ciamemazina, levomepromazina, tioridazina, trifluoperazina), benzamidas…»
AEMPS, section 4.5 · Open on CIMA
Moderateinhibidores de la ECAclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): La toma de inhibidores de la ECA (por ejemplo, captopril, enalapril) durante el tratamiento clortalidona crea el riesgo de una caída grave…»
AEMPS, section 4.5 · Open on CIMA
ModerateInsulin
«También son posibles interacciones con las siguientes combinaciones: El efecto de estos medicamentos puede verse debilitado por el uso concomitante de clortalidona. Puede ser necesario ajustar la…»
AEMPS, section 4.5 · Open on CIMA
Moderateinsulinaclass named in the label
«También son posibles interacciones con las siguientes combinaciones: El efecto de estos medicamentos puede verse debilitado por el uso concomitante de clortalidona. Puede ser necesario ajustar la…»
AEMPS, section 4.5 · Open on CIMA
Moderatelaxantesclass named in the label
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Diuréticos kaliuréticos (p. ej., furosemida), glucocorticoides, ACTH, carbenoxolona, penicilina G, salicilatos, laxantes estimulantes…»
AEMPS, section 4.5 · Open on CIMA
Moderatemedicamentos que prolongan el QTclass named in the label
«Sustancias que pueden desencadenar torsades de pointes: Si estas sustancias se administran concomitantemente con clortalidona, especialmente en caso de hipopotasemia, existe un mayor riesgo de…»
AEMPS, section 4.5 · Open on CIMA
ModerateMethotrexate
«También son posibles interacciones con las siguientes combinaciones: Medicamentos citostáticos (por ejemplo, ciclofosfamida, fluorouracilo, metotrexato)»
AEMPS, section 4.5 · Open on CIMA
ModerateMethyldopa
«Inhibidores de la ECA (por ejemplo, captopril, enalapril): Otros diuréticos, otros medicamentos antihipertensivos (p. ej., betabloqueantes, antagonistas del calcio, inhibidores de la ECA…»
AEMPS, section 4.5 · Open on CIMA
ModerateMoxifloxacin
«Sustancias que pueden desencadenar torsades de pointes: - otros: bepridil, cisaprida, difemanil, eritromicina i.v., halofantrina, mizolastina, pentamidina, esparfloxacino, moxifloxacino, vincamina…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Chlortalidone used for?

Chlortalidone is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Resistant arterial hypertension (evidence tier B), Symptomatic edema (evidence tier C). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Chlortalidone?

Common side effects of Chlortalidone (≥ 1 in 100): Hypokalaemia: weakness, muscle cramps, palpitations, Hyponatraemia, especially in the first two weeks and in older people, Hyperuricaemia, Dizziness and orthostatic hypotension, Impaired glucose tolerance. See the Safety section for uncommon and serious reactions.

Is Chlortalidone safe during pregnancy?

Is Chlortalidone compatible with breastfeeding?

Who should not take Chlortalidone?

Chlortalidone is contraindicated in: Hypersensitivity to chlorthalidone or to any excipient; Anuria; Severe renal impairment (creatinine clearance below 30 ml/min); Severe hepatic impairment; Refractory hypokalaemia and states with large potassium losses. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 12/06/2025

Other drugs in this group

Eplerenone, Furosemide, Hydrochlorothiazide, Indapamide, Spironolactone, Torasemide, Triamterene