Chlortalidone

Chlortalidone is approved as a single agent for the treatment of:

• cardiac, nephrogenic or hepatic edema.
• in arterial hypertension
• in heart failure
• in renal diabetes insipidus when other drugs are not an option

There is a clear risk to the development of the human fetus. Chlortalidone can reduce blood flow to the placenta, enters the fetal bloodstream and may cause electrolyte imbalances. Chlortalidone should not be administered during pregnancy. Since chlortalidone passes into breast milk, nursing mothers should avoid its use.

In children, the lowest effective dose should be selected, e.g., 0.5-1 mg/kg/48 h as the initial dose and 1.7 mg/kg/48 h as the maximum dose.

In elderly patients and in patients with mild renal impairment, it is also recommended to use the lowest effective dose, since in elderly patients the excretion of chlortalidone is slower than in healthy younger adults.

Rare: neutropenia, hyperglycemia.

Thiazide-induced hypokalemia or hypomagnesemia may favor the occurrence of digitalis-induced cardiac arrhythmias.

Acute pancreatitis has been sporadically described with chlortalidone (other confirmed drugs include: azathioprine, furosemide, sulfonamides, tetracyclines, estrogens, valproic acid , L-asparaginase) (Dobrilla G et al 1985; Mallory A et al 1980).

Chlortalidone may increase the risk of UWAs to allopurinol and amantadine. Furthermore, enhance the blood sugar elevating effect of diazoxide, and reduce the effect of norepinephrine and epinephrine.

Colestipol and colestyramine reduce the absorption of chlortalidone.

Concomitant administration of vitamin D or calcium salts may increase serum calcium while concomitant administration of ciclosporin may increase the risk of hyperuricemia and gouty complications.

Dermatologic UAWs:

• Exanthema (caveat: presence of sulfonamide hypersensitivity).
• Fixed drug exanthema (Cuervo-Pardo N et al 2018).
• Phototoxic reactions also under the clinical presentation of pseudoporphyria (Baker EJ ET al 1989).
• Necrotizing vasculitides (Björnberg A et al 1965).
• Other: Cases of sexual erectile dysfunction under chlortalidone ingestion have been described several times (Stessman J et al. 1980).

The concomitant administration of chlortalidone with other antihypertensive agents (e.g., beta-blockers, vasodilators, calcium antagonists, methyldopa, beta-receptor blockers, vasodilators, calcium antagonists, ACE inhibitors), other diuretics, tricyclic antidepressants, barbiturates, or phenothiazines potentiates the antihypertensive effect.

Chlortalidone may raise blood lithium levels.

Chlortalidone may potentiate the effects of curare derivatives and cytotoxic agents (e.g., cyclophosphamide, methotrexate).

The potassium-lowering effect of chlortalidone may be increased by corticosteroids, ACTH, amphotericin, various laxatives, carbenoxol, and other drugs. The potassium lowering effect of chlortalidone may be increased by corticosteroids, ACTH, amphotericin, various laxatives, carbenoxolol or other potassium excreting agents.

The dose of insulin and oral antidiabetic agents may need to be adjusted.

Concomitant administration of non-steroidal anti-inflammatory drugs (e.g., indomethacin, acetylsalicylic acid) may attenuate the effect of chlortalidone.

High-dose treatment with salicylates may increase the toxic effect of salicylate on the CNS.

Hypersensitivity to the substance chlortalidone, to antimicrobial sulfonamides or related drugs e.g. sulfonylureas.

renal failure (creatinine clearance < 30 ml/min)

glomerulonephritis and anuria

severe liver failure

treatment-resistant potassium deficiency or increased potassium loss

sodium deficiency

elevated calcium level

elevated uric acid levels with associated clinical symptoms (e.g., history of gout or uric acid stones)

hypertension during pregnancy.

Trade names and dosage forms

Chlortalidone as a single substance: Hygroton®^, Hydrosan®

+ atenolol: Teneretic®

+ metoprolol: Prelis comp®

+ Atenolol/+Hydralazine: Tri-Normin®

There is controversy as to whether chlortalidone is superior to hydrochlorothiazide in the treatment of hypertension with respect to the rate of cardiovascular events (CVEs). Some studies suggest that chlortalidone reduces CVEs more than hydrochlorothiazide and in this respect chlortalidone is the preferred thiazide-type diuretic for hypertension in patients at high risk of CVEs (Dorsch MP et al 2011). No adverse effects occur when switching from hydrochlorothiazide to chlortalidone (Matthews KA ET AL. 2013).

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2. Björnberg A et al (1965) A cause of necrotising vasculitis? Lancet. 7420: 982-983.
3. Cooney D et al (2015) Diuretics for hypertension: hydrochlorothiazide or chlorthalidone? Cleve Clin J Med 82:527-533.
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6. Cuervo-Pardo N et al (2018) Bullous fixed drug eruption secondary to chlorthalidone. J Allergy Clin Immunol Pract 6:252-253.
7. Dorsch MP et al (2011) Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 57:689-694.
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