LTHT Drug and Therapeutics Committee Summary Metolazone for the treatment of fluid overload in heart failure and renal failure including nephrotic syndrome Supported for use NHS Leeds Traffic Light Classification: Amber Level 1 Application summary - February 2013 • Metolazone is a thiazide-like diuretic. It is not chemically related to thiazides but acts at the same site of the renal tubules and blocks sodium reabsorbtion by acting on the sodium-chloride channel. • The usual dose of metolazone is 2.5mg three times a week to 5mg daily. • For solely commercial reasons metolazone has been withdrawn from the UK market but an alternative is available from Canada as an import. Although unlicensed in the UK, it does possess a license in Canada. • Metolazone is added to treatment with a loop diuretic when the patient has not had an adequate diuretic response to the maximum dose of the loop diuretic. It is usually used as a short term measure but may be used at higher doses for longer periods depending on patient response. • Metolazone has an established role in the treatment of resistant oedema in HF. The experience of the cardiologists is that the addition of metolazone to loop diuretics produces a better diuretic effect than the addition of bendroflumethiazide. • Although not quoted in NICE guidance, SIGN recommends that careful addition of metolazone can often cause a useful natriuresis. • When used, careful monitoring of blood is essential to prevent abnormalities in sodium, creatinine and other electrolytes. Weight loss, fluid balance and symptoms of fluid overload will also be monitored by the clinical team. • There is no randomised clinical trial data of metolazone in heart failure, but it is an established part of diuretic treatment. • Although usage is low, around fifty patients a year, metolazone is still more effective in patients with reduced renal impairment when compared to alternative thiazide diuretics such as bendroflumethiazide, something which is also a common feature of heart failure • The Canadian product contains a colorant which is not permitted in foodstuffs or medicines in the EU. The reason for this is not due to safety issues, but due to the lack of an EU evaluation. The colourant is approved in the USA for use in pharmaceuticals. Place in therapy Addition to high dose loop diuretics for fluid overload in heart failure and renal failure Drug and Therapeutics Decision Summary - July 2012 • Approved in line with application Compiled from the original formulary application and the Drug and Therapeutics Committee minutes Russell Kaye, Trainee Specialist Pharmacist Dave Abbott, Senior Medicines Information Pharmacist The Leeds Medicines Information Service [email protected] .