Chlortalidone

Uses

Chlortalidone is used for the management of hypertension. Chlortalidone is used for adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy.

Chlortalidone is also used to associated treatment for these conditions: Calcium Nephrolithiasis

How Chlortalidone works

Chlortalidone prevents reabsorption of sodium and chloride through inhibition of the Na+/Cl- symporter in the cortical diluting segment of the ascending limb of the loop of Henle. Reduction of sodium reabsorption subsequently reduces extracellular fluid and plasma volume via an osmotic, sodium-driven diuresis. By increasing the delivery of sodium to the distal renal tubule, Chlortalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism. The exact mechanism of chlorthalidone's anti-hypertensive effect is under debate, however, it is thought that increased diuresis results in decreased plasma and extracellular fluid volume which therefore requires decreased cardiac output and overall lowers blood pressure. Chlortalidone has also been shown to decrease platelet aggregation and vascular permeability, as well as promote angiogenesis in vitro, which is thought to be partly the result of reductions in carbonic anhydrase–dependent pathways. These pathways may play a role in chlorthalidone's cardiovascular risk reduction effects.

Dosage

Chlortalidone dosage

Therapy should be initiated with the lowest possible dose and then titrated according to individual patient response. A single dose given in the morning with food is recommended; divided doses are unnecessary.

Edema: Up to 50 mg daily.

Hypertension: 25 mg daily in the morning, increased to 50 mg daily if necessary.

Heart failure: 25-50 mg daily in the morning, increased if necessary to 100-200 mg daily (reduce to lowest effective dose for maintenance).

Maintenance doses may often be lower than initial doses and should be adjusted according to the individual patient.

Side Effects

Dry mouth, thirst, nausea, vomiting, feeling weak, drowsy, restless, or light-headed, fast or uneven heartbeat, muscle pain or weakness, urinating less than usual or not at all, easy bruising or bleeding, unusual weakness, red or purple spots on skin, numbness or tingly feeling, nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools.

Precaution

Renal impairment: Chlortalidone dosage should be reduced in moderate renal failure - every 24 or 48 h - and should not be used in advanced renal failure.

Liver disease: There is a risk of precipitating hepatic encephalopathy in patients with liver cirrhosis and ascites.

Use in pregnancy: It is better to avoid Chlortalidone as it crosses the placenta.

Use in Lactation: In lactating mother, significant amount of Chlortalidone enter breast milk; like other long-acting thiazides, it can suppress lactation. Chlortalidone should not be prescribed for lactating mother.

Interaction

Chlortalidone may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic peripheral adrenergic blocking drugs.

Food Interaction

• Take with food. Food may increase bioavailability.

Chlortalidone Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Chlortalidone Cholesterol interaction

[Moderate] Thiazide diuretics may increase serum triglyceride and cholesterol levels, primarily LDL and VLDL.

Whether these effects are dose-related and sustained during chronic therapy are unknown.

Patients with preexisting hyperlipidemia may require closer monitoring during thiazide therapy, and adjustments made accordingly in their lipid-lowering regimen

Chlortalidone Drug Interaction

Moderate: metoprolol, metoprolol, metoprolol, metoprolol, cholecalciferol, cholecalciferolUnknown: aspirin, aspirin, aspirin, aspirin, ubiquinone, ubiquinone, apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid

Chlortalidone Disease Interaction

Major: anuria, electrolyte losses, liver disease, lupus erythematosus, renal function disordersModerate: asthma, diabetes, hyperlipidemia, hyperparathyroidism, hyperuricemia, thyroid function tests

Volume of Distribution

Chlortalidone has been shown to rapidly concentrate within erythrocytes and subsequently equilibrate via a slow diffusion back into the serum compartment, resulting in a large volume of distribution.

Half Life

40-50 hours

Elimination Route

Approximately 50% of the administered dose is excreted unmetabolized through the kidney, and excretion is characterized by biphasic elimination with a rapid phase followed by a slow secretory phase.

Pregnancy & Breastfeeding use

Pregnancy category B. Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from chlorthalidone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Patients with anuria and known hypersensitivity to Chlortalidone or other sulfonamide-derived drugs.

Special Warning

Pediatric Use: Safety and effectiveness of Chlortalidone tablets in pediatric patients have not been established.

Geriatric Use: Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Acute Overdose

Symptoms of acute overdosage include nausea, weakness, dizziness, and disturbances of electrolyte balance. The oral LD50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote, but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.

Storage Condition

Store in a cool & dry place, away from children

Innovators Monograph

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