Addendum: Metolazone is now available in an unlicensed preparation. Some centres may consider using the newly available preparation in preference to bendroflumethiazide, particularly in patients with a very low GFR.
Sanofi-Aventis has ceased to manufacture and distribute metolazone. Metolazone is sometimes used for patients with heart failure and intractable fluid retention as an adjunct to loop diuretics as part of 'sequential nephron blockade'.
Most studies of combination therapy (loop+thiazide) have used metolazone, but Channer showed that metolazone and bendrofluazide were equally effective in inducing diuresis in patients with resistant oedema when added to intravenous frusemide.*
Our advice is to switch patients receiving metolazone to bendroflumethiazide when a patient's supplies run out, at a dose of 2.5 mg, increasing to 5mg, if indicated.
Unlicensed preparations of metolazone are available at significantly increased cost. Both 2.5mg and 5mg tablets should be available. Som of these foreign unlicensed preparations have colorants unlicensed in the EU, although the MHRA has still authorised them to be imported. Local advice (eg from pharmacy) should be sought where needed. Generic manufacturers may eventually step into the breach, however there has been no movement in this respect so far.
*Channer KS, McLean KA, Lawson-Matthew P, Richardson M. Combination diuretic treatment in severe heart failure: a randomised controlled trial. Br Heart J 1994;71:146-150