Drug Breakdown: METOLAZONE

Day 1: A potent long-acting oral thiazide-like diuretic, #metolazone was discovered in the 1970s. Can be used in combination with loop diuretics for acute heart failure where it may potentiate effect & is postulated to help with diuretic resistance. Mostly used short-term, but some require longterm management

Day 2: #metolazone is licensed in adults for oedema of heart failure or kidney disease, as well as hypertension. Licensed in the UK as Xaqua® as 5 mg divisible tablet (care re switching as imports had other strengths/differences in bioavailability). Dose is 2.5 to 5 mg daily a.m.

Day 3: #metolazone has good oral absorption;take same time daily relative to meal;cmax~1.5hrs. High Vd & protein binding. ~ 10% hydroxylated to inactive metabolites/some enterohepatic recycling. Most excreted unchanged in urine/ small % biliary excretion. T½ 8-10hrs. Note that states of oedema can affect bioavailability for #metolazone; monitor for response variability

Day 4: #metolazone inhibits NaCl symporter & thus Na reabsorption. The action is predominantly in distal tubule, increasing urine volume & reducing fluid accumulation. Also, some Na absorption inhibition occurs in proximal tubule. K+excretion may be less affected compared to other diuretics. #metolazone is believed not to induce the reninangiotensin-aldosterone system, which supports overcoming issues with diuretic resistance. Electrolyte monitoring required