Chlortalidone (chlorthalidone, US)
P : Caution when used during pregnancy
L : Caution when used during lactation
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C03BA04 - chlortalidone (or chlorthalidone)
Chlorthalidone is an oral antihypertensive/diuretic. It is a monosulfamyl diuretic that differs chemically from thiazide diuretics in that a double-ring system is incorporated in its structure. It is 2-chloro-5(1-hydroxy-3-oxo-1- isoindolinyl) benzenesulfonamide with the Molecular Formula C14H11ClN2O4S and weight: 338.76
Treatment of arterial hypertension, essential or nephrogenic or isolated systolic. Treatment of stable, chronic heart failure of mild to moderate degree (New York Heart Association, NYHA: functional class II or III).
Oedema of specific origin
• Ascites due to cirrhosis of the liver in stable patients under close control.
• Oedema due to nephrotic syndrome.
· Diabetes Insipidus.
|Dosage & Administration||
The dosage of Chlortalidone should be individually titrated to give the lowest effective dose; this is particularly important in the elderly. Chlortalidone should be taken orally, preferably as a single daily dose at breakfast time.
The recommended starting dose is 25mg/day. This is sufficient to produce the maximum hypotensive effect in most patients. If the decrease in blood pressure proves inadequate with 25mg/day, then the dose can be increased to 50mg/day. If a further reduction in blood pressure is required, additional hypertensive therapy may be added to the dosage regime.
Stable, chronic heart failure (NYHA: functional class II /III):
The recommended starting dose is 25 to 50mg/day, in severe cases it may be increased up to 100 to 200mg/day. The usual maintenance dose is the lowest effective dose, eg 25 to 50mg/day either daily or every other day. If the response proves inadequate, digitalis or an ACE inhibitor, or both, may be added.
Oedema of specific origin
The lowest effective dose is to be identified by titration and administered over limited periods only. It is recommended that doses should not exceed 50mg/day.
Initially 100mg twice daily but reducing where possible to a daily maintenance dose of 50mg.
The lowest effective dose should also be used in children. For example, an initial dose of 0.5 to 1mg/kg/48hours and a maximum dose of 1.7mg/kg/48hours have been used.
Elderly patients and patients with renal impairment:
The lowest effective dose of Chlortalidone is also recommended for patients with mild renal insufficiency and for elderly patients.
In elderly patients, the elimination of chlortalidone is slower than in healthy young adults, although absorption is the same. Therefore, a reduction in the recommended adult dosage may be needed. Close medical observation is indicated when treating patients of advanced age with chlortalidone.
Chlortalidone and the thiazide diuretics lose their diuretic effect when the creatinine clearance is <30ml/min.
Signs and symptoms: In poisoning due to an overdosage the following signs and symptoms may occur: dizziness, nausea, somnolence, hypovolaemia, hypotension and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms.Treatment: There is no specific antidote to Chlortalidone. Gastric lavage, emesis or activated charcoal should be employed to reduce absorption. Blood pressure and fluid and electrolyte balance should be monitored and appropriate corrective measures taken. Intravenous fluid and electrolyte replacement may be indicated.
Chlortalidone is contraindicated in severe renal (creatinine clearance <30ml/min) or hepatic failure, addison's disease, preexisting hypercalcaemia, bronchial asthma; hypersensitivity; severe allergy, hypertension during pregnancy.
Existing fluid and electrolyte disturbances, hepatic cirrhosis, severe heart failure, hyperuricaemia, mild to moderate renal impairment. Elderly. Monitor fluid and electrolyte balance. Kidney or liver disease; diabetes; gout; hyperlipidaemia and ventricular extra systoles.
|Adverse Drug Reaction(s)||Chlortalidone may result in following adverse effects - dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, oliguria, hypotension, fatigue, muscle cramps and GI disturbances, nausea, vomiting, constipation, diarrhoea, anorexia. Diabetes and gout may be precipitated. Impotence. Raised blood levels of glucose, urates, lipids and calcium. Reduced levels of K and magnesium. Raised CPK levels.
Potentially Fatal: Rare. Severe hyponatraemia and idiosyncratic hypersensitivity.
|Drug Interaction(s)||NSAIDs antagonise hypotensive action. Suppresses action of oral anticoagulants due to reduced prothrombin activity. Increased risk of hypokalaemia when corticosteroids are given concurrently.
Potentially Fatal: Potentiates bone marrow suppression caused by anticancer drugs. Diuretic-induced vol depletion can potentiate aminoglycoside nephrotoxicity. Impairs action of oral hypoglycaemic agents. Enhances digitalis toxicity due to hypokalaemia. vol depletion enhances lithium toxicity, conversely, sudden withdrawal of diuretics may result in subtherapeutic levels of circulating lithium. Prolonged paralysis with tubocurarine due to hypokalaemia.
|Pregnancy Category (FDA)
Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).
Category D if used during gestational hypertension. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Mechanism of actionChlortalidone is an oral, long acting antihypertensive/diuretic. It is a monosulfamyl diuretic that acts by enhancing the excretion of sodium and chloride ions, and water by interfering with the transport of sodium ions across the renal tubular epithelium. Their primary site of action appears to be at the cortical diluting segment in the nephron of the loop of Henle.
Onset: 2 hr.
Duration: 48-72 hr.
Absorption: Erratic absorption from the GI tract (oral).
Distribution: Binds to red blood cells; crosses the placenta and enters breast milk. Protein-binding: Weak.
Excretion: Urine (as unchanged drug); 40-60 hr (elimination half-life).
|Storage||Store at 15-30°C.|
|| See Prescribing Information from Brand Manufacturer |||Manufacturer's|