Adult: For cases associated with heart failure or renal diseases (e.g. nephrotic syndrome): Slow and incompletely bioavailable formulation: 5-10 mg daily. Doses may be increased to 20 mg daily if necessary. Max: 80 mg daily. Dosage must be individualised according to the severity of condition and patient response. Elderly: Lower initial doses may be necessary.
Oral Hypertension
Adult: Alone or in combination with other antihypertensives: Slow and incompletely bioavailable formulation: 2.5-5 mg daily; alternatively, initial dose of 1.25 mg daily may be given. Dosage must be individualised and may be adjusted after 3-4 weeks according to response. Maintenance: 5 mg on alternate days. Rapidly absorbed and completely bioavailable formulation: Initially, 0.5 mg once daily, may be increased to 1 mg once daily if necessary. Elderly: Lower initial doses may be necessary.
Administration
May be taken with or without food. Preferably taken as a single dose in the morning to avoid nocturia.
Contraindications
Hepatic coma or precoma, anuria.
Special Precautions
Patient with diabetes mellitus or prediabetes, gout, primary adrenal insufficiency (Addison’s disease), SLE, and hypokalaemia; sulfonamide hypersensitivity. Patient undergoing surgery, including bariatric surgery. Do not interchange the slow and incompletely bioavailable formulation, with the rapidly absorbed and completely bioavailable formulation as they are not therapeutically equivalent at similar doses. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Orthostatic hypotension, hypersensitivity reactions (e.g. angioedema, bronchospasm), azotaemia, oliguria, hyperuricaemia, gout precipitation, electrolyte imbalance (e.g. severe hypokalaemia, hyponatraemia, hypercalcaemia, hypochloraemic alkalosis, hypomagnesaemia), photosensitivity, hyperglycaemia, glycosuria; SLE exacerbation or activation. Blood and lymphatic system disorders: Agranulocytosis, aplastic anaemia, hypoplastic anaemia, leucopenia, thrombocytopenia, haemoconcentration. Cardiac disorders: Chest discomfort, chest pain, palpitations, syncope. Ear and labyrinth disorders: Vertigo. Eye disorders: Transient blurred vision. Gastrointestinal disorders: Constipation, diarrhoea, nausea, vomiting, abdominal pain. General disorders and administration site conditions: Fatigue, weakness. Hepatobiliary disorders: Cholestatic jaundice, hepatitis. Investigations: Increased BUN or serum creatinine. Metabolism and nutrition disorders: Hypovolaemia, hypophosphataemia. Musculoskeletal and connective tissue disorders: Arthralgia, chills, muscle cramps or spasm. Nervous system disorders: Dizziness, headache, drowsiness, neuropathy, paraesthesia, restlessness. Psychiatric disorders: Depression. Skin and subcutaneous tissue disorders: Skin rash, pruritus, urticaria, petechiae, purpura. Potentially Fatal: Stevens-Johnson Syndrome, toxic epidermal necrolysis.
Avoid excessive exposure to sunlight and UV light. Do not switch between brands unless instructed by your doctor.
Monitoring Parameters
Correct electrolyte imbalances before treatment initiation. Monitor blood pressure, renal function, serum electrolyte levels, fluid balance, and uric acid periodically during treatment. Assess for signs of electrolyte disturbance, hypotension, and hypersensitivity reactions.
Overdosage
Symptoms: Dizziness, drowsiness, syncope, electrolyte imbalance, plasma volume depletion, depressed respiration, gastrointestinal irritation, hypermotility and lethargy progressing to coma (high doses). Management: Supportive treatment. Protect the airways when emptying stomach contents, particularly stuporous or comatose patients. Maintain hydration, electrolyte balance, respiration, CV and renal function as necessary.
Drug Interactions
Severe volume depletion and electrolyte imbalance with furosemide. May increase the risk of orthostatic hypotension with other antihypertensives, barbiturates and narcotics. May increase the risk of hypokalaemia with corticosteroids. May increase plasma lithium concentrations and the risk of lithium toxicity. May diminish antihypertensive effect with salicylates, NSAIDs, or methenamine. May impair the therapeutic efficacy of anticoagulants. Increased risk of serious arrhythmias with digitalis glycosides.
Food Interaction
Alcohol may increase the orthostatic hypotensive effect of metolazone.
Lab Interference
May cause a false-negative aldosterone/renin ratio (ARR).
Action
Description: Mechanism of Action: Metolazone, a diuretic pharmacologically similar to thiazides, blocks Na reabsorption mainly in the distal convoluted tubules and to a lesser extent in proximal convoluted tubules. It causes an increased Na and water excretion, and K and hydrogen ion excretion. Onset: Diuresis: Approx 60 minutes. Duration: Diuretic effect: ≥24 hours. Pharmacokinetics: Absorption: Variable absorption depending on the formulation. Slowly and incompletely absorbed from the gastrointestinal tract. Bioavailability: Approx 65%. In some counties, rapidly absorbed and enhanced bioavailability formulation may be available. Distribution: Crosses the placenta and enters breast milk. Volume of distribution: 113 L. Plasma protein binding: 95% (approx 50-70% to RBCs; 15-33% to plasma proteins). Metabolism: Not metabolised to a substantial extent. Excretion: Mainly via urine (80-95% as unchanged drug). Elimination half-life: 8-14 hours.
Chemical Structure
Metolazone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4170, Metolazone. https://pubchem.ncbi.nlm.nih.gov/compound/Metolazone. Accessed Oct. 26, 2020.
C03BA08 - metolazone ; Belongs to the class of low-ceiling sulfonamide diuretics.
References
Anon. Metolazone. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/09/2020.Anon. Metolazone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/09/2020.Buckingham R (ed). Metolazone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/09/2020.Joint Formulary Committee. Metolazone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/09/2020.Metolazone Tablet (Mylan Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 09/09/2020.Metolazone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com/. Accessed 19/10/2020.Metoz 5 mg Tablet (DéGa International Pharma Corp). MIMS Philippines. http://www.mims.com/philippines. Accessed 09/09/2020.
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