Xuret

Uses

Xuret is used for the treatment of salt and water retention including:

• Edema accompanying congestive heart failure
• Edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function.

Xuret is also used for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.

Xuret is also used to associated treatment for these conditions: Edema, Mild Hypertension, Moderate Hypertension

How Xuret works

The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Xuret acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Xuret does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.

Dosage

Xuret dosage

Effective dosage of Xuret tablets should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with Xuret tablets should be titrated to gain an initial therapeutic response and to determine the minimal dose possible to maintain the desired therapeutic response.

Usual Single Daily Dosage Schedules: Suitable initial dosages will usually fall in the ranges given.

Edema of Cardiac Failure: Xuret tablets 5 to 20 mg once daily.

Edema of Renal Disease: Xuret tablets 5 to 20 mg once daily.

Mild to Moderate Essential Hypertension: Xuret tablets 2.5 to 5 mg once daily.New patients- If considered desirable to switch patients currently on Zaroxolyn tablets and other formulations of Xuret that share its slow and incomplete bioavailability to Mykrox , the dose should be determined by titration starting at one tablet (0.5 mg) once daily and increasing to two tablets (1 mg) once daily if needed.

Treatment Of Edematous States: The time interval required for the initial dosage to produce an effect may vary.Diuresisand saluresis usually begin within one hour and persist for 24 hours or longer. When a desired therapeutic effect has been obtained, it may be advisable to reduce the dose if possible. The daily dose depends on the severity of the patient's condition, sodium intake, and responsiveness. A decision to change the daily dose should be based on the results of thorough clinical and laboratory evaluations. If antihypertensive drugs or diuretics are given concurrently with Xuret tablets, more careful dosage adjustment may be necessary. For patients who tend to experience paroxysmal nocturnaldyspnea, it may be advisable to employ a larger dose to ensure prolongation of diuresis and saluresis for a full 24-hour period.

Treatment Of Hypertension: The time interval required for the initial dosage regimen to show effect may vary from three or four days to three to six weeks in the treatment of elevated blood pressure. Doses should be adjusted at appropriate intervals to achieve maximum therapeutic effect.

Side Effects

Chest pain, palpitation, necrotising angiitis, orthostatic hypotension, syncope, venous thrombosis, vertigo, volume depletion; depression, dizziness, chills, drowsiness, fatigue, restlessness, headache, lightheadedness; petechiae, photosensitivity, hypersensitivity reactions; gout attacks, electrolyte disturbances; abdominal bloating, diarrhoea, abdominal pain, anorexia, constipation, epigastric distress, nausea, xerostomia, pancreatitis, vomiting; impotence; aplastic anaemia, thrombocytopenia, haemoconcentration, leukopenia; cholestatic jaundice, hepatitis; joint pain, muscle cramps, weakness, neuropathy, paraesthesia; blurred vision; increased BUN, glucosuria.

Toxicity

Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.

Precaution

Pre-diabetes or DM; gout; SLE; hepatic and renal impairment; hypercholesterolaemia. Correct electrolyte disturbances prior to therapy. Risk of cross-sensitivity with sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides and loop diuretics. Lactation.

Interaction

Hypotensive and nephrotoxic effects of ACE inhibitors may be enhanced. Absorption may be reduced with bile acid sequestrants. Hyperglycaemic effect may be enhanced with diazoxide. May increase serum concentration and QTc-prolonging effect of dofetilide. May reduce lithium excretion. Hypotensive effect may be increased with alcohol.

Food Interaction

• Take with food. Food reduces irritation.

Xuret 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.

Xuret 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

Xuret Drug Interaction

Moderate: fluticasone / salmeterol, carvedilol, insulin glargine, furosemide, metoprolol, metoprolol, polyethylene glycol 3350, cholecalciferolMinor: warfarinUnknown: aspirin, rosuvastatin, apixaban, omega-3 polyunsaturated fatty acids, atorvastatin, pregabalin, clopidogrel, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid

Xuret Disease Interaction

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

Elimination Route

Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.

Half Life

Approximately 14 hours.

Elimination Route

Most of the drug is excreted in the unconverted form in the urine.

Pregnancy & Breastfeeding use

Pregnancy 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).

If used in gestational HTN: Pregnancy Category D: 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).

Contraindication

Anuria; hepatic coma or pre-coma. Pregnancy.

Acute Overdose

Symptoms: Orthostatic hypotension, dizziness, drowsiness, syncope, haemoconcentration and haemodynamic changes due to plasma volume depletion.

Management: Symptomatic and supportive.

Innovators Monograph

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