Amiloride + Furosemide

Severe: Contraindicated.

Hypersensitivity to furosemide, amiloride, sulfonamides or sulfonamide-derived drugs. Hypovolaemia or dehydration, hyperkalaemia (serum potassium level >5.5 mmol/L), electrolyte imbalance (e.g. severe hypokalaemia, severe hyponatraemia), Addison's disease, pre-comatose state associated with cirrhosis; anuria or renal failure with anuria not responding to furosemide, renal failure due to nephrotoxic or hepatotoxic agents, renal failure associated with hepatic coma. Severe renal impairment (CrCl <30 mL/min/1.73 m²). Lactation. Concomitant use of potassium-sparing diuretics or potassium supplements.

Patient with hypotension or those at risk from a significant decrease in blood pressure; prediabetes or diabetes mellitus, gout, SLE, hypoproteinaemia (including cases associated with nephrotic syndrome), partial urinary outflow obstruction (e.g. prostatic hyperplasia, micturition impairment); hepatorenal syndrome. Not recommended for patients at high risk for radiocontrast nephropathy. Correct hypotension, hypovolaemia and significant electrolyte or acid-base disturbances before treatment initiation. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy.

Significant: Fluid or electrolyte loss, hypovolaemia and dehydration (particularly in the elderly), metabolic alkalosis, urinary retention, SLE exacerbation or activation, hepatic encephalopathy (particularly in patients with hepatocellular insufficiency), impaired glucose tolerance; symptomatic hypotension which may lead to dizziness, fainting or loss of consciousness.
Blood and lymphatic system disorders: Eosinophilia, thrombocytopenia, haemoconcentration.
Ear and labyrinth disorders: Hearing disorders, tinnitus.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation.
General disorders and administration site conditions: Malaise.
Hepatobiliary disorders: Cholestasis.
Immune system disorders: Hypersensitivity reactions.
Investigations: Decreased serum calcium levels; increased serum cholesterol, triglyceride levels, and serum transaminases.
Nervous system disorders: Headache, paraesthesia.
Renal and urinary disorders: Tubulointerstitial nephritis, renal failure.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, photosensitivity, bullous dermatitis, erythema multiforme.
Vascular disorders: Thrombosis, vasculitis.
Potentially Fatal: Hyperkalaemia.

Monitor renal function, serum electrolytes (e.g. potassium, sodium), blood pressure, and blood glucose levels regularly.

Symptoms: Hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias (including AV block and ventricular fibrillation), severe hypotension which may progress to shock, thrombosis, acute renal failure, delirious states, flaccid paralysis, apathy, and confusion. Management: Symptomatic and supportive treatment. Reverse dehydration and correct electrolyte imbalance (particularly hyperkalaemia). May induce emesis or perform gastric lavage.

May result in significant fall in blood pressure with other diuretics, cardiac glycosides, antihypertensive agents, or other drugs that can lower blood pressure. May increase the serum levels and risk of cardiotoxicity/nephrotoxicity of lithium. May antagonise the diuretic effect and result in acute renal failure with certain NSAIDs (e.g. aspirin, indometacin). May reduce the therapeutic effects of antidiabetics and pressor amines. May potentiate the effects of salicylates, theophylline, and curare-type muscle relaxants. May increase the risk of hypokalaemia with carbenoxolone, corticosteroids, β₂-sympathomimetics (in high doses) and laxatives (prolonged use). Reduced effects with probenecid, methotrexate, phenytoin and other drugs that undergo significant renal tubular secretion.
Amiloride: Increased potassium levels and risk of hyperkalaemia with potassium salts, drugs which decrease potassium excretion, NSAIDs or ACE inhibitors. May increase blood digoxin concentrations.
Furosemide: May increase the toxic effects of nephrotoxic drugs and chloral hydrate. Decreased absorption with sucralfate. May potentiate the ototoxic effects of aminoglycosides and other ototoxic drugs. May enhance the ototoxic and nephrotoxic effects of cisplatin. Reduced plasma concentration with aliskiren. Increased risk of gouty arthritis with ciclosporin. May result in impaired renal function with high doses of certain cephalosporins. May inhibit the binding of thyroid hormones to carrier proteins when given with levothyroxine which may lead to a transient increase in free thyroid hormone levels and reduction in total thyroid hormone levels. May reduce the renal elimination of probenecid, methotrexate, and other drugs that undergo significant renal tubular secretion.
Potentially Fatal: Amiloride: Enhanced hyperkalaemic effects with potassium-sparing diuretics.
Furosemide: Increased risk of mortality in elderly with dementia when used concomitantly with risperidone.

May result in a false-negative aldosterone/renin ratio (ARR).

Description:
Mechanism of Action: Amiloride, a weak potassium-sparing diuretic, blocks epithelial sodium channels in the late distal convoluted tubule and collecting duct, thereby inhibiting sodium reabsorption from the lumen. This activity effectively decreases intracellular sodium and reduces the function of sodium/potassium-ATPase, resulting in potassium retention and reduced calcium, magnesium, and hydrogen excretion.
Furosemide is a potent loop diuretic. It acts primarily by inhibiting sodium and chloride reabsorption in the ascending loop of Henle and both the proximal and distal renal tubules, interfering with the chloride-binding cotransport system, thereby increasing the excretion of sodium, chloride and water.
Synonym(s): Furosemide: Frusemide.
Onset: Amiloride: Within 2 hours.
Furosemide: Diuresis: 30-60 minutes. Symptomatic improvement in acute pulmonary oedema: Within 15-20 minutes prior to the diuretic effect.
Duration: Amiloride: Approx 24 hours.
Furosemide: 6-8 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.
Furosemide: Fairly rapidly absorbed from the gastrointestinal tract. Bioavailability: 47-64%. Time to peak plasma concentration: 1-2 hours.
Distribution: Amiloride: Volume of distribution: 350-380 L.
Furosemide: Crosses the placenta and enters breast milk. Plasma protein binding: 91-99%, mainly to albumin.
Metabolism: Furosemide: Undergoes minimal metabolism in the liver.
Excretion: Amiloride: Via urine (approx 50% as unchanged drug); faeces (approx 40%). Elimination half-life: 6-9 hours.
Furosemide: Via urine (50%); faeces (as unchanged drug). Elimination half-life: 0.5-2 hours.

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.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3440, Furosemide. https://pubchem.ncbi.nlm.nih.gov/compound/Furosemide. Accessed Aug. 14, 2023.

Store below 25°C.

Diuretics

C03EB01 - furosemide and potassium-sparing agents ; Belongs to the class of high-ceiling diuretics in combination with potassium-sparing agents. Used as diuretics.

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