Metolazone is a thiazide-like diuretic. It is particularly effective when combined with a loop diuretic (even in renal failure) and so is useful to off-load persistent oedema and to maintain target weight in end stage heart failure. Profound diuresis may occur, so electrolytes and weight should be monitored. For most patients, treatment with metolazone will be short term but a minority of patients will require ongoing treatment.

Metolazone was only available as an unlicensed special-order item in the UK but a licensed product, Xaqua, is now available.

Xaqua tablets bioavailability is up to approximately two-fold higher than for other metolazone preparations. Therefore, a dose adjustment may be necessary and individualised titration based on patient's response and tolerability is advised if switching from Xaqua tablets to another metolazone product, or vice versa.

As patients maintained on metolazone are already tightly monitored and dosed according to response it is not expected that this will be a problem.

Metolazone is used to achieve diuresis and/or to maintain dry weight in heart failure patients.

Treatment for this indication should be recommended by a specialist in heart failure.

The GP may prescribe following recommendation by the heart failure specialist.

To be initiated on recommendation of heart failure specialist.

• Metolazone is available as a 5mg tablet. Patients are usually treated with 2.5mg once or twice a week in addition to a loop diuretic.

• Dose could be increased to a maximum of 5mg daily (rarely used)

• Aim for a maximum daily weight loss of 0.5kg

• Patients should weigh themselves daily to ensure they are maintaining their target weight or achieving acceptable weight loss

• BP and blood chemistry (e.g., serum creatinine, urea, potassium, sodium and eGFR) should be checked within one week of initiation and if there is a change of dose. Then recheck every 7-14 days depending on patient’s stability.

• If patient is maintained on metolazone and treatment is stable, monitor renal function and electrolytes once a month.

(see BNF for a full list of drug interactions)

• Excessive diuresis

• Postural hypotension

• Metabolic and electrolyte disturbances

• Mild gastro-intestinal disturbances

• Muscle pain and cramps

• May cause adverse reactions affecting the ability to drive a vehicle and/or to operate machines, such as dizziness and fatigue.

• May increase sensitivity to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors.

• Less commonly; blood disorders, pancreatitis, intrahepatic cholestasis, cardiac arrhythmias, headache, dizziness, paraesthesia, visual disturbances, psychotic depression, confusion, lethargy, drowsiness, weakness, restlessness (sometimes resulting in insomnia), apathy, seizures, hepatic encephalopathy, neuropathy, oliguria, vasculitis, urticaria, chills, joint pain and hypersensitivity reactions.

1. BNF online https://bnf.nice.org.uk/
2. Xaqua 5mg tablets. Summary of Product Characteristics Accessed 25/10/2022 https://www.medicines.org.uk/emc/product/13419/smpc
3. Reducing readmissions for congestive heart failure. R. Hoyt, Lester Bowling Am Fam Physician. 2001 Apr 15;63(8):1593-1599
4. Theresa A McDonagh et al, 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC, European Heart Journal, Volume 42, Issue 36, 21 September 2021, Pages 3599–3726, Available at:  https://doi.org/10.1093/eurheartj/ehab368 (Accessed 07.03.22). Correction published 21 December 2021, https://doi.org/10.1093/eurheartj/ehab670
5. Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Rosenberg J, Gustafsson F, Galatius S, Hildebrandt P Cardiovasc Drugs Ther. 2005 Aug;19(4):301-6.
6. Salahudin, M, Shah H, Muneeb U and Altaf A (2019) Comparing the sodium excreting efficacy of furosemide and indapamide combination against furosemide and metolazone combination in congestive heart failure patients: a randomized control trial. The Journal of the Pakistan Medical Association 69 (12): 1794-1799.

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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