Metolazone

Metolazone is indicated 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.

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

Metolazone is a thiazide-like diuretic. It inhibits reabsorption of sodium in the distal tubules resulting in increased excretion of sodium and water, as well as potassium and hydrogen ions.

Effective dosage of Metolazone tablets should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with Metolazone 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: Metolazone tablets 5 to 20 mg once daily.

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

Mild to Moderate Essential Hypertension: Metolazone tablets 2.5 to 5 mg once daily.

New patients- If considered desirable to switch patients currently on Zaroxolyn tablets and other formulations of Metolazone 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. Diuresis and 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 Metolazone tablets, more careful dosage adjustment may be necessary. For patients who tend to experience paroxysmal nocturnal dyspnea, 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.

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.

Anuria; hepatic coma or pre-coma. Pregnancy.

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.

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).

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.

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

Management: Symptomatic and supportive.

Thiazide diuretics & related drugs.