Chlortalidone

Structural formula
( R ) shape (top) and ( S ) shape (bottom)
General
Non-proprietary name	Chlortalidone
other names	( RS ) -2-chloro-5- (1-hydroxy-3-oxo-1-isoindolinyl) -benzenesulfonamide
Molecular formula	C 14 H 11 ClN 2 O 4 S
External identifiers / databases
CAS number 77-36-1 EC number 201-022-5 ECHA InfoCard 100,000,930 PubChem 2732 DrugBank DB00310 Wikidata Q425289
Drug information
ATC code	C03 BA04 C03 BB04 C03 EA06
Drug class	Diuretic
properties
Molar mass	338.77 g · mol -1
Physical state	firmly
Melting point	224-226 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 319 P: 305 + 351 + 338
Toxicological data	> 5000 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Chlortalidon ( INN ) or Chlorthalidon ( USAN ) (original trade name Hygroton ^® ; manufacturer: Novartis ; distributed in DE by Mibe ) is a diuretic drug . It is a thiazide analogue that belongs to the group of thiazide diuretics due to the same principle of action . Chemically, chlortalidone belongs to the sulfonamides and is used in the treatment of high blood pressure and to flush out water retention in tissue . Chlorthalidone is used both as a single substance used as a component of combination drugs (for example, together with. Beta blockers such as atenolol or metoprolol or with the Rauvolfia - alkaloid reserpine ).

Clinical information

Application areas (indications)

Chlortalidon is approved as a single substance in Germany for the treatment of

• Accumulation of water in body tissues ( edema ), by dysfunction of heart , liver or kidney are caused
• high blood pressure
• Weak heart muscle ( heart failure )
• Wasserharnruhr ( renal diabetes insipidus ) when other medicines out of the question

There are no approvals for the treatment of renal diabetes insipidus in Austria or Switzerland.

Combination drugs, which contain other drugs in addition to chlortalidone, are used exclusively to treat high blood pressure.

Contraindications (contraindications)

Hypersensitivity to chlortalidone and other sulfonamides or related drugs ( sulfonylureas ); Kidney failure ( creatinine clearance less than 30 ml / min); Glomerulonephritis (acute inflammation of the kidneys); lack of urine production ( anuria ); severe liver failure ; treatment-resistant potassium deficiency or increased potassium loss; Sodium deficiency ; increased calcium level , increased uric acid level with clinical side effects (e.g. gout or a history of uric acid stones); High blood pressure during pregnancy .

Drug interactions

• The simultaneous administration of chlortalidone with other antihypertensive agents (e.g. guanethidine , methyldopa , beta blockers , vasodilators , calcium antagonists , ACE inhibitors ), other diuretics , tricyclic antidepressants , barbiturates or phenothiazines increases the antihypertensive effect. This interaction may be desirable, but it can also lead to circulatory problems.
• Chortalidone can raise blood lithium levels. Therefore, patients receiving lithium treatment must be particularly monitored. Since lithium can trigger polyuria , chlortalidone can have a paradoxical effect, that is, lower urine excretion.
• Chlorthalidone the effect of at anesthesia used curare - derivatives as well as cytotoxic agents (eg. Cyclophosphamide , methotrexate reinforce).
• The potassium-lowering effects of chlortalidone can be enhanced by corticosteroids , ACTH , β2-agonists , amphotericin , laxatives , carbenoxolol, or other potassium-secreting agents.
• The dose of insulin and oral anti-diabetic drugs may need to be adjusted. U. can be adjusted.
• The simultaneous administration of anti-inflammatory agents (e.g. indomethacin , acetylsalicylic acid ) can weaken the antihypertensive and diuretic effects of chlorotalidone
• In the case of high-dose treatment with salicylates , the toxic effect of the salicylate on the central nervous system can be intensified.
• Thiazide-induced hypokalaemia or hypomagnesaemia may favor the occurrence of digitalis-induced cardiac arrhythmias.
• Chlortalidone can increase hypersensitivity reactions to allopurinol, increase the risk of undesirable effects of amantadine, increase the blood sugar- increasing effect of diazoxide , and weaken the effect of uric acid-lowering agents, noradrenaline and adrenaline .
• Anticholinergics (e.g. atropine , biperiden ) can increase the bioavailability of chlortalidone while colestipol and colestyramine reduce the absorption of chlortalidone.
• Concomitant administration of vitamin D or calcium salts can lead to an increase in serum calcium, while concomitant administration of ciclosporin can increase the risk of hyperuricemia and gout-like complications.

Use during pregnancy and breastfeeding

There is a clear risk to the development of the human fetus . Chlortalidone can reduce blood flow to the placenta and enter the fetal bloodstream , where it can cause electrolyte imbalances. Thrombocytopenia has also been reported in the newborn. Chlortalidone should not be used during pregnancy . Since chlortalidone is excreted in breast milk , breastfeeding mothers should refrain from using it.

Special patient groups

In children, the lowest effective dose should be chosen, e.g. B. 0.5-1 mg / kg / 48 h as the starting dose and 1.7 mg / kg / 48 h as the maximum dose. The lowest effective dose is also recommended in the
elderly and in patients with mild renal impairment . Despite the same uptake of the drug , the elimination of chlortalidone is slower in older patients than in healthy younger adults. If patients are treated with chlortalidone at an advanced age, careful medical supervision is therefore indicated. Chlortalidone loses its diuretic effect in kidney failure ( creatinine clearance below 30 ml / min).

Other Information

History

Chlortalidon was developed by JR Geigy (today: Novartis ) in the 1950s and marketed as hygroton in 1959 . The introduction of chlortalidone was an important medical advance as it was the first long-acting diuretic used to treat high blood pressure.

Studies

The ALLHAT studies conducted in North America examined the use of chlortalidone in the treatment of high blood pressure compared to newer antihypertensive drugs. Despite considerable methodological criticism after the studies were published, it can be assumed that chlorthalidone protects against the secondary diseases of high blood pressure (e.g. stroke ) than the alpha blocker doxazosin , the calcium antagonist amlodipine or the ACE inhibitor lisinopril , but not overall mortality or lowers the death rate from heart attacks.

Trade names and dosage forms

Important note: Trade names and dosage forms of medicinal substances are not subject to any standardization. They can therefore differ in individual countries.

All dosage forms containing chlortalidone require a prescription .

Germany

• Chlortalidone as a single substance: Hygroton tablets (25 and 50 mg chlortalidone)
• Chlortalidon in combination with Atenolol: Teneretic mite tablets (Atenolol 50 mg, Chlortalidon 12.5 mg) or Teneretic tablets (Atenolol 100 mg, Chlortalidon 25 mg) as well as numerous generic drugs
• Chlortalidone in combination with metoprolol : Prelis comp prolonged-release tablets (metoprolol tartrate 200 mg, chlortalidone 25 mg)
• Chlortalidon in a triple combination: Tri-Normin 25 (atenolol 25 mg, chlortalidone 12.5 mg, hydralazine 25 mg) and Tri-Normin 50 (atenolol 50 mg, chlortalidone 25 mg, hydralazine 50 mg)

Austria

• Chlortalidone as a single substance: Hydrosan tablets (25 mg chlortalidone)
• Chlortalidon in combination with Atenolol : Teneretic mite tablets (Atenolol 50 mg, Chlortalidon 12.5 mg) or Teneretic tablets (Atenolol 100 mg, Chlortalidon 25 mg) as well as numerous generic drugs
• Chlortalidon in combination with Celiprolol : Selecturon (Celiprolol 200 mg, Chlortalidon 25 mg)

Switzerland

• Chlortalidone as a single substance: Hygroton tablets (25 mg chlortalidone)
• Chlortalidone in combination with Atenolol: Tenoretic mite tablets (Atenolol 50 mg, Chlortalidone 12.5 mg) or Tenoretic tablets (Atenolol 100 mg, Chlortalidone 25 mg) as well as generics
• Chlortalidone in combination with metoprolol: Logroton prolonged-release tablets (metoprolol tartrate 200 mg, chlortalidone 25 mg)
• Chlortalidon in combination with Oxprenolol : Slow-Trasitensin tablets (Oxprenolol 160 mg, Chlortalidon 25 mg)

Individual evidence

1. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 364, ISBN 978-0-911910-00-1 .
2. ↑ ^{a b c} data sheet chlorthalidone from Sigma-Aldrich , accessed on October 22, 2016 ( PDF ).
3. ↑ technical information Hygroton (December 2004), Mibe Arzneimittel GmbH Brehna.
4. ↑ technical information Hygroton (March 2003), Novartis Pharma AG Bern.
5. ↑ ALLHAT Officers et al. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 : 2981-97, PMID 12479763 .
6. ↑ ALLHAT Officers et al. Major Cardiovascular Events in Hypertensive Patients Randomized to Doxazosin vs Chlorthalidone: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) . JAMA 2000; 283 : 1967-75, PMID 10789664 .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !