Drugs List

Therapeutic Indications

Uses

Ascites and oedema associated with hepatic cirrhosis
Congestive heart failure
Hypertension
Oedema
Potassium conservation when given with thiazide or loop diuretic

Contraindications

Hyperkalaemia where serum potassium over 5.5mmol / l
Acute renal failure
Addison's disease
Anuria
Breastfeeding
Diabetic nephropathy
Pregnancy
Renal impairment - glomerular filtration rate below 10ml/minute
Severe progressive renal disorder

Precautions and Warnings

Cardiopulmonary disorder
Children under 18 years
Elderly
Diabetes mellitus
Electrolyte imbalance
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hereditary fructose intolerance
Lactose intolerance
Metabolic acidosis
Metabolic alkalosis
Raised blood urea
Renal impairment - glomerular filtration rate 10 - 50ml/minute
Respiratory acidosis
Severe hepatic disorder

Reduce dose in patients with glomerular filtration rate 10-50ml/min
Advise ability to drive/operate machinery may be affected by side effects
Not all available products are licensed for all age groups
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Monitor blood urea
Monitor serum electrolytes
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue treatment before glucose tolerance test
May affect results of some laboratory tests
Discontinue if hyperkalaemia occurs
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food

Determine renal function prior to therapy in patients with or suspected of having diabetes mellitus. Discontinue amiloride at least 3 days before a glucose-tolerance test.

Particular caution should be used in severely ill patients who may develop respiratory or metabolic acidosis (e.g. cardiopulmonary disease or decompensated diabetes). Acidosis may be associated with rapid increases in plasma potassium and therefore these patients may experience an altered balance of intracellular-extracellular potassium.

Monitor patients for signs of hyperkalaemia. Clinical, laboratory and ECG observations should be performed.
Particular care should be taken with the elderly and patients with hepatic cirrhosis or cardiac oedema with known renal involvement, or those undergoing vigorous diuretic therapy.

Patients with hepatic cirrhosis are more likely to experience side effects as they are less tolerant of shifts in electrolyte balance. Higher rates of encephalopathy, manifested by tremors, confusion, coma and increased jaundice may be seen in these patients.

Pregnancy and Lactation

Pregnancy

Amiloride hydrochloride is contraindicated during pregnancy.

The routine use of diuretics in the treatment of gestational hypertension is not indicated due to risk of hypovolaemia. Amiloride does not appear to show evidence of risk when used for indications other than preeclampsia and gestational hypertension (Briggs, 2015)

Animal studies using amiloride in mice and rabbits at respectively 25 and 20 times the maximum recommended human dose found no evidence of foetal harm. The combination of amiloride and acetazolamide, however, resulted in abnormal development of the ureter and kidney in mice (Briggs, 2015).

Amiloride is known to cross the placenta in mice and rabbits. There are limited reports describing the passage of amiloride across the human placenta. The molecular weight (about 230 for the free base) is low enough that transfer to the human foetus should be expected (Briggs, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Amiloride hydrochloride is contraindicated in breastfeeding.

It is unknown whether amiloride is excreted in human breast milk. The molecular weight (about 230 for the free base) is low enough, that passage into the milk should be expected (Briggs, 2015). Milk production can decrease with the use of diuretics, especially if there is an existing lactation deficiency.

Amiloride is excreted in the milk of lactating rats at concentrations higher than that measured in blood (Hale, 2011).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function
Abnormal liver function tests
Aggravation of peptic ulcer
Agitation
Alopecia
Angina pectoris
Anorexia
Aplastic anaemia
Arrhythmias
Arthralgia
Back pain
Bladder spasm
Chest pain
Confusion
Constipation
Cough
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Encephalopathy
Fatigue
Flatulence
Gastro-intestinal haemorrhage
Gout
Headache
Heart block
Hyperkalaemia
Hypochloraemia
Hyponatraemia
Impotence
Increased frequency of micturition
Increased intra-ocular pressure
Increased thirst
Increased uric acid level
Insomnia
Jaundice
Joint pain
Malaise
Minor psychiatric disturbances
Muscular cramps
Nasal congestion
Nausea
Neck pain
Nervousness
Neutropenia
Orthostatic hypotension
Painful extremities
Palpitations
Paraesthesia
Polyuria
Pruritus
Rash
Reduced libido
Shoulder pain
Somnolence
Tinnitus
Tremor
Vertigo
Visual disturbances
Vomiting
Weakness

Presentation

Oral formulations containing amiloride hydrochloride

Drugs List

Therapeutic Indications

Uses

Ascites and oedema associated with hepatic cirrhosis
Congestive heart failure
Hypertension
Oedema
Potassium conservation when given with thiazide or loop diuretic

Dosage

Adults

Children

Neonates

Patients with Renal Impairment

Contraindications

Hyperkalaemia where serum potassium over 5.5mmol / l
Acute renal failure
Addison's disease
Anuria
Breastfeeding
Diabetic nephropathy
Pregnancy
Renal impairment - glomerular filtration rate below 10ml/minute
Severe progressive renal disorder

Precautions and Warnings

Cardiopulmonary disorder
Children under 18 years
Elderly
Diabetes mellitus
Electrolyte imbalance
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hereditary fructose intolerance
Lactose intolerance
Metabolic acidosis
Metabolic alkalosis
Raised blood urea
Renal impairment - glomerular filtration rate 10 - 50ml/minute
Respiratory acidosis
Severe hepatic disorder

Reduce dose in patients with glomerular filtration rate 10-50ml/min
Advise ability to drive/operate machinery may be affected by side effects
Not all available products are licensed for all age groups
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Monitor blood urea
Monitor serum electrolytes
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Discontinue treatment before glucose tolerance test
May affect results of some laboratory tests
Discontinue if hyperkalaemia occurs
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effect enhanced by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food

Determine renal function prior to therapy in patients with or suspected of having diabetes mellitus. Discontinue amiloride at least 3 days before a glucose-tolerance test.

Particular caution should be used in severely ill patients who may develop respiratory or metabolic acidosis (e.g. cardiopulmonary disease or decompensated diabetes). Acidosis may be associated with rapid increases in plasma potassium and therefore these patients may experience an altered balance of intracellular-extracellular potassium.

Monitor patients for signs of hyperkalaemia. Clinical, laboratory and ECG observations should be performed.
Particular care should be taken with the elderly and patients with hepatic cirrhosis or cardiac oedema with known renal involvement, or those undergoing vigorous diuretic therapy.

Patients with hepatic cirrhosis are more likely to experience side effects as they are less tolerant of shifts in electrolyte balance. Higher rates of encephalopathy, manifested by tremors, confusion, coma and increased jaundice may be seen in these patients.

Pregnancy and Lactation

Pregnancy

Amiloride hydrochloride is contraindicated during pregnancy.

The routine use of diuretics in the treatment of gestational hypertension is not indicated due to risk of hypovolaemia. Amiloride does not appear to show evidence of risk when used for indications other than preeclampsia and gestational hypertension (Briggs, 2015)

Animal studies using amiloride in mice and rabbits at respectively 25 and 20 times the maximum recommended human dose found no evidence of foetal harm. The combination of amiloride and acetazolamide, however, resulted in abnormal development of the ureter and kidney in mice (Briggs, 2015).

Amiloride is known to cross the placenta in mice and rabbits. There are limited reports describing the passage of amiloride across the human placenta. The molecular weight (about 230 for the free base) is low enough that transfer to the human foetus should be expected (Briggs, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Amiloride hydrochloride is contraindicated in breastfeeding.

It is unknown whether amiloride is excreted in human breast milk. The molecular weight (about 230 for the free base) is low enough, that passage into the milk should be expected (Briggs, 2015). Milk production can decrease with the use of diuretics, especially if there is an existing lactation deficiency.

Amiloride is excreted in the milk of lactating rats at concentrations higher than that measured in blood (Hale, 2011).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function
Abnormal liver function tests
Aggravation of peptic ulcer
Agitation
Alopecia
Angina pectoris
Anorexia
Aplastic anaemia
Arrhythmias
Arthralgia
Back pain
Bladder spasm
Chest pain
Confusion
Constipation
Cough
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Encephalopathy
Fatigue
Flatulence
Gastro-intestinal haemorrhage
Gout
Headache
Heart block
Hyperkalaemia
Hypochloraemia
Hyponatraemia
Impotence
Increased frequency of micturition
Increased intra-ocular pressure
Increased thirst
Increased uric acid level
Insomnia
Jaundice
Joint pain
Malaise
Minor psychiatric disturbances
Muscular cramps
Nasal congestion
Nausea
Neck pain
Nervousness
Neutropenia
Orthostatic hypotension
Painful extremities
Palpitations
Paraesthesia
Polyuria
Pruritus
Rash
Reduced libido
Shoulder pain
Somnolence
Tinnitus
Tremor
Vertigo
Visual disturbances
Vomiting
Weakness

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

Summary of product characteristics: Amilamont 5mg/5ml Oral Solution. Rosemont Pharmaceuticals Limited. Revised March 2016.

Summary of product characteristics: Amiloride Tablets BP 5mg. Actavis UK Ltd. Revised September 2016.

Summary of product characteristics: Amiloride Tablets 5mg. Wockhardt UK Ltd. Revised August 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 June 2017