Adult: In cases of cardiac, renal or hepatic origin, including iatrogenic oedema: Initially, 50-200 mg daily in 1 or 2 divided doses, preferably in the morning, may reduce to 25-50 mg on alternate days or intermittently according to patient’s response. Elderly: Dose reduction may be required. Child: >12 years Recommended dose: Initially, 1 mg/kg daily.
Oral Hypertension
Adult: As monotherapy or in combination with other antihypertensive agents: Usual dose: 25-50 mg daily. Maintenance: 25-50 mg on alternate days. Elderly: Dose reduction may be required. Child: >12 years Recommended dose: Initially, 1 mg/kg daily.
Renal Impairment
Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Contraindications
Addison’s disease, hypercalcaemia, symptomatic hyperuricaemia, refractory hypokalaemia, hyponatraemia, anuria. Severe renal and hepatic impairment. Concomitant use with lithium.
Special Precautions
Patient with diabetes, gout, or SLE. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: May aggravate diabetes, gout or SLE; hypokalaemia. Blood and lymphatic system disorders: Blood dyscrasias Gastrointestinal disorders: Pancreatitis, diarrhoea. Hepatobiliary disorders: Intrahepatic cholestasis. Immune system disorders: Hypersensitivity reactions. Investigations: Altered plasma lipid concentrations. Metabolism and nutrition disorders: Hyponatraemia, hypercalcaemia, hypochloraemic alkalosis, hyperuricaemia, hyperglycaemia. Reproductive system and breast disorders: Impotence. Skin and subcutaneous tissue disorders: Rash, photosensitivity. Vascular disorders: Postural hypotension.
Monitoring Parameters
Monitor renal function; electrolyte levels and signs of blood dyscrasias (prolonged use, particularly in elderly).
Overdosage
Symptoms: Diuresis, lethargy (progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration), gastrointestinal irritation, hypermotility, transient elevation of BUN level. Management: Symptomatic and supportive treatment. Empty stomach by gastric lavage. Institute supportive measures as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.
Drug Interactions
May increase sensitivity to and risk of toxicity of digitalis. May result in antagonistic effect with NSAIDs (e.g. indometacin, ketorolac), corticosteroids, estrogens and combined oral contraceptives. Enhanced hypotensive effect with ACE inhibitors, angiotensin II antagonists, β-blockers, Ca channel blockers, nitrates, adrenergic neurone blockers, general anaesthetics, anxiolytics, hypnotics, MAOI, phenothiazines, alprostadil, aldesleukin, levodopa, baclofen, moxisylyte, tizanidine, and α-blockers (e.g. prazosin). Increased risk of nephrotoxicity and ototoxicity with cisplatin. May exacerbate hypokalaemia with acetazolamide, corticosteroids, amphotericin, reboxetine, β2 sympathomimetics, theophylline, and loop diuretics. Increased risk of nephrotoxicity and hypermagnesaemia with ciclosporin. Increased cardiotoxicity with disopyramide, amiodarone, cardiac glycosides, flecainide, quinidine. Antagonise effects of lidocaine, mexiletine and antidiabetic agents. Increased risk of ventricular arrhythmias with amisulpride, sotalol, atomoxetine, sertindole, terfenadine. May increase risk of postural hypotension with TCAs. May increase the risk of hypersensitivity with allopurinol. May increase risk of lithium toxicity. May reduce absorption with colestipol and colestyramine. Increased risk of hyponatraemia with aminoglutethimide, carbamazepine, chlorpropamide. Increased the risk of hypercalcaemia with calcium salts, toremifene and vitamin D.
Food Interaction
Increased risk of postural hypotension with alcohol.
Action
Description: Mechanism of Action: Hydroflumethiazide is a thiazide diuretic that acts mainly on the distal convoluted tubule to the thick segment of the end limb of the loop of Henle. It inhibits the distal tubular re-absorption of Na and Cl ions resulting in increased urinary loss of K and Mg. Additionally, it increases the renal tubular re-absorption of Ca. Onset: Approx 2 hours. Duration: Up to 24 hours. Pharmacokinetics: Absorption: Rapidly but incompletely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-4 hours. Distribution: Volume of distribution: 6.4 L/kg. Plasma protein binding: Approx 75%. Excretion: Via urine (40-80% as unchanged drug). Plasma elimination half-life: 12.4-26.9 hours.
Chemical Structure
Hydroflumethiazide Source: National Center for Biotechnology Information. PubChem Database. Hydroflumethiazide, CID=3647,
https://pubchem.ncbi.nlm.nih.gov/compound/3647#section=2D-Structure&fullscreen=true
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