Adult: Amiloride 2.5 mg and hydrochlorothiazide 25 mg tab Amiloride 5 mg and hydrochlorothiazide 50 mg tab
As monotherapy or adjunct with other antihypertensive agents for patients where K depletion is anticipated: Initially, 2.5-5 mg/25-50 mg once daily. Dose may be increased to 5-10 mg/50-100 mg daily as a single dose or in 2 divided doses if necessary. Dosage recommendations and available fixed-dose combinations may vary between countries and among individual products (refer to specific product guidelines). Elderly: Initiate at the lower end of the dosing range.
Oral Congestive heart failure
Adult: Amiloride 2.5 mg and hydrochlorothiazide 25 mg tab
For patients where K depletion is anticipated: Initially, 2.5 mg/25 mg once daily, may be increased to a Max of 10 mg/100 mg daily if necessary. Optimal dose is determined based on diuretic response and serum K level. Once initial diuresis is achieved, may reduce dose for maintenance treatment. Maintenance treatment may be on an intermittent basis.
Amiloride 5 mg and hydrochlorothiazide 50 mg tab
For patients who develop hypokalaemia when thiazides/other kaliuretic diuretics are used alone, or when maintenance of normal K levels is clinically important (e.g. digitalised patients): Initially, 5 mg/50 mg once daily. Dose may be increased to 10 mg/100 mg daily as a single dose or in 2 divided doses if necessary. Optimal dose is determined based on diuretic response and serum K level. Once initial diuresis is achieved, may reduce dose for maintenance treatment. Maintenance treatment may be on an intermittent basis. Dosage recommendations and available fixed-dose combinations may vary between countries and among individual products (refer to specific product guidelines). Elderly: Initiate at the lower end of the dosing range.
Oral Hepatic cirrhosis
Adult: Amiloride 2.5 mg and hydrochlorothiazide 25 mg tab Amiloride 5 mg and hydrochlorothiazide 50 mg tab
For cases associated with ascites and oedema: Initially, 5 mg/50 mg daily, may be increased to 10 mg/100 mg daily if necessary. Maintenance dose may be lower than those needed to initiate diuresis; dose reduction must be done when the patient's weight is stabilised. Dosage recommendations and available fixed-dose combinations may vary between countries and among individual products (refer to specific product guidelines). Elderly: Initiate at the lower end of the dosing range.
What are the brands available for Amiloride + Hydrochlorothiazide in Hong Kong?
Amithiazide
Apo-Amilzide
Sefaretic
Administration
Amiloride + Hydrochlorothiazide Should be taken with food.
Contraindications
Hypersensitivity to amiloride, hydrochlorothiazide or sulfonamide-derived drugs. Hyperkalaemia (serum K level >5.5 mmol/L), hypercalcaemia; Addison's disease; anuria, acute or chronic renal failure, severe or progressive renal disease, diabetic nephropathy; severe hepatic failure, pre-coma associated with hepatic cirrhosis. Severe renal impairment. Concomitant use with other K-sparing agents (e.g. spironolactone, triamterene), K supplements, K-containing salt substitutes, or K-rich diet (except in cases of severe and/or refractory hypokalaemia under careful monitoring).
Special Precautions
Patient with diabetes mellitus, moderate or high cholesterol concentrations, parathyroid disease, gout, SLE, severe illness where metabolic or respiratory acidosis may occur (e.g. cardiopulmonary disease, uncontrolled diabetes), bronchial asthma; progressive hepatic disease. Patients with increases in BUN >10.7 mmol/L, serum creatinine >0.13 mmol/L, or whole blood urea values >10 mmol/L must not receive amiloride + hydrochlorothiazide without careful, frequent, and continuous monitoring of serum electrolytes, creatinine and BUN levels. Not indicated for initial therapy except in patients in whom the development of hypokalaemia cannot be risked. Hypokalaemia may cause cardiac arrhythmia and may sensitise/exaggerate the heart's response to the toxic effects of digitalis (e.g. increased ventricular arrhythmia). Avoid diuretics in the postoperative period following bariatric surgery. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Electrolyte disturbances (e.g. hypochloraemic alkalosis, hypomagnesaemia, hyponatraemia, hypokalaemia [especially with brisk diuresis of thiazide therapy]), dehydration; hyperuricaemia, precipitation of gout, increased cholesterol and triglyceride levels, impaired glucose tolerance, increased BUN levels, decreased urinary Ca excretion, precipitation of azotaemia (particularly in patients with renal impairment); hypersensitivity reactions, ocular effects (e.g. acute transient myopia, acute angle-closure glaucoma, choroidal effusion with visual field defect), photosensitivity, increased risk of non-melanoma skin cancer (prolonged use [≥3 years]), exacerbation or activation of SLE. Cardiac disorders: Angina pectoris, tachycardia. Ear and labyrinth disorders: Vertigo. Eye disorders: Visual disturbances. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation, flatulence. General disorders and administration site conditions: Fatigue, malaise, weakness. Metabolism and nutrition disorders: Thirst, anorexia, appetite changes. Musculoskeletal and connective tissue disorders: Back pain, leg pain, muscle cramps, joint pain. Nervous system disorders: Headache, dizziness, paraesthesia, sleepiness. Psychiatric disorders: Depression, insomnia, nervousness. Renal and urinary disorders: Dysuria, incontinence, nocturia, renal dysfunction including renal failure. Respiratory, thoracic and mediastinal disorders: Dyspnoea, nasal congestion. Skin and subcutaneous tissue disorders: Rash, pruritus, diaphoresis. Vascular disorders: Flushing, orthostatic hypotension. Potentially Fatal: Hyperkalaemia, cardiac arrhythmia.
Avoid prolonged exposure to sunlight and UV rays; if exposure cannot be avoided, wear sunscreen or protective clothing when going outdoors.
Monitoring Parameters
Closely monitor serum K levels, particularly during initial therapy and dose adjustments. Monitor other serum electrolytes, intake and output, blood pressure, daily weight, and renal function. Assess for signs and symptoms of hyperkalaemia, other electrolyte disturbances, skin photosensitivity, and skin lesions/cancer.
Overdosage
Symptoms: Amiloride: Fluid depletion (e.g. dehydration, hypotension) and electrolyte imbalance. Hydrochlorothiazide: Hypochloraemia, hypokalaemia, hyponatraemia, and dehydration. Hypokalaemia may accentuate cardiac arrhythmias if digitalis is given. Management: Symptomatic and supportive treatment. May administer activated charcoal within 1 hour of ingestion. May consider to induce emesis and/or perform gastric lavage. Monitor serum electrolyte concentrations, renal function, and fluid and electrolyte replacement. Monitor and correct blood pressure if needed.
Drug Interactions
May decrease the excretion of lithium which may increase the risk of lithium toxicity. Increased risk of nephrotoxicity and ototoxicity with cisplatin. Increased risk of hyponatraemia with carbamazepine, chlorpropamide, or aminoglutethimide. NSAIDs may reduce the antihypertensive, diuretic and natriuretic effects of amiloride and hydrochlorothiazide.
Amiloride: Increased risk of hyperkalaemia with ACE inhibitors, angiotensin II antagonists, indometacin, ciclosporin or tacrolimus.
Hydrochlorothiazide: May potentiate orthostatic hypotension with barbiturates or narcotics. May reduce arterial responsiveness to pressor amines (e.g. norepinephrine, epinephrine). May reduce the therapeutic effect of antidiabetic drugs (e.g. oral agents, insulin). Additive effect with other antihypertensive drugs. Reduced absorption with colestyramine and colestipol. May increase the plasma concentration of fluconazole. May intensify thiazide-induced electrolyte depletion (particularly hypokalaemia) and antagonise the diuretic effect with corticosteroids or ACTH. May increase the responsiveness to non-depolarising skeletal muscle relaxants (e.g. tubocurarine). Toxic effects of cardiac glycosides may be increased by the hypokalaemic and hypomagnesaemic effects of hydrochlorothiazide. Potentially Fatal: Enhanced hyperkalaemic effect with other K-sparing diuretics (e.g. spironolactone, triamterene), K supplements and K-containing salt substitutes.
Food Interaction
Hydrochlorothiazide: Orthostatic hypotensive effect may be potentiated by alcohol.
Lab Interference
May cause false-negative aldosterone/renin ratio (ARR).
Hydrochlorothiazide: May interfere with parathyroid function tests. May reduce serum iodine (protein-bound) without signs of thyroid disturbance.
Action
Description: Mechanism of Action: Amiloride and hydrochlorothiazide exerts diuretic and antihypertensive activity primarily through the hydrochlorothiazide component. The amiloride component counteracts the excessive K loss (and to a lesser extent Mg loss) associated with hydrochlorothiazide.
Amiloride is a K-sparing diuretic that has weak natriuretic, diuretic, and antihypertensive effects. It blocks the epithelial Na channels in the late distal convoluted tubule (DCT) and collecting duct, thereby inhibiting Na reabsorption from the lumen. This action effectively decreases intracellular Na and reduces Na+/K+-ATPase function, resulting in K retention and decreased excretion of Ca, Mg, and hydrogen.
Hydrochlorothiazide is a thiazide diuretic and an antihypertensive agent. It exerts the diuretic effect by inhibiting Na reabsorption in the distal tubules, thereby increasing the excretion of Na, K, chloride, and hydrogen ions and consequently water. The exact mechanism of antihypertensive effect is unknown; however, its hypotensive effect is possibly partly a result of peripheral resistance reduction. Onset: Amiloride: Within 2 hours.
Hydrochlorothiazide: Approx 2 hours. Duration: Amiloride: Approx 24 hours.
Hydrochlorothiazide: 6-12 hours. Pharmacokinetics: Absorption: Amiloride: Incompletely absorbed from the gastrointestinal tract. Food decreases the extent of absorption. Bioavailability: Approx 50%. Time to peak plasma concentration: 3-4 hours.
Hydrochlorothiazide: Rapidly and well absorbed from the gastrointestinal tract. Bioavailability: 65-75%. Time to peak plasma concentration: Approx 1-5 hours. Distribution: Amiloride: Volume of distribution: 350-380 L.
Hydrochlorothiazide: Crosses the placenta and enters breast milk. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%. Excretion: Amiloride: Via urine (approx 50% as unchanged drug); faeces (approx 40%). Elimination half-life: 6-9 hours.
Hydrochlorothiazide: Via urine (≥61% as unchanged drug). Elimination half-life: Approx 5-15%.
Chemical Structure
Amiloride Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 16231, Amiloride. https://pubchem.ncbi.nlm.nih.gov/compound/Amiloride. Accessed Sept. 24, 2024.
Hydrochlorothiazide Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3639, Hydrochlorothiazide. https://pubchem.ncbi.nlm.nih.gov/compound/Hydrochlorothiazide. Accessed Oct. 24, 2023.
C03EA01 - hydrochlorothiazide and potassium-sparing agents ; Belongs to the class of low-ceiling diuretics in combination with potassium-sparing agents. Used as diuretics.
References
AA-Amilzide Tablet 50 mg/5 mg (Pharmaforte [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/03/2024.Amiloride and Hydrochlorothiazide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 04/03/2024.Amiloride Hydrochloride and Hydrochlorothiazide Tablet (Teva Pharmaceuticals USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/03/2024.Amiloride. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 04/03/2024.Amiloride; Hydrochlorothiazide, HCTZ. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 04/03/2024.Buckingham R (ed). Amiloride Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/03/2024.Buckingham R (ed). Hydrochlorothiazide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/03/2024.Co-amilozide Tablets 2.5 mg/25 mg (Genethics Europe Limited). MHRA. https://products.mhra.gov.uk. Accessed 18/07/2024.Co-amilozide Tablets 5 mg/50 mg (Ennogen Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 04/03/2024.Hydrochlorothiazide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 04/03/2024.Joint Formulary Committee. Co-amilozide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2024.Moduride Tablet (Duopharma [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/03/2024.Pharmacy Retailing Pty Ltd. Moduretic 50 mg/5 mg Tablet data sheet 3 May 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 04/03/2024.
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