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Precautions and Warnings

Correct hypovolaemia and hypotension before initiation of treatment.

NSAIDs may antagonise the action of diuretics. Patients should be advised not to take NSAIDs unless advised by a clinician.

Rapid mobilisation of oedema may cause circulatory collapse, particularly in elderly patients. This should be born in mind when amiloride and bumetanide is given in high doses.

Use with caution in patients suspected of electrolyte disturbance.

Regularly monitor fluid and serum electrolyte status, particularly sodium, potassium, chloride and bicarbonate.

Hyponatraemia, hypochloraemia and raised blood urea may occur during vigorous diuresis especially in seriously ill patients. Careful monitoring of serum electrolytes and urea should be undertaken in these patients.

Patients with hepatic impairment should be treated with caution due to an increased risk of encephalopathy.

Diabetes mellitus - glucose tolerance may be decreased and diabetes may be aggravated. Monitor blood and urinary glucose in patients with diabetes mellitus and those suspected of latent diabetes (which may become manifest). Diabetics may require an increase in hypoglycaemic agents. Discontinue treatment before glucose tolerance test.

Chronic renal failure patients should remain under constant hospital supervision.
Discontinue if blood urea increases or oliguria/anuria occur during treatment for oedema due to renal insufficiency.

In prostatic hypertrophy or impaired micturition urinary retention may occur. This can be avoided by the use of low doses and less potent diuretics initially. An adequate urinary output should be established before initiating treatment.

Serum uric acid levels may be increased and acute attacks of gout may be precipitated.

Use in caution in patients taking nephrotoxic or ototoxic drugs.

Potassium supplements or drugs that may increase serum potassium levels should only be co-administered cautiously.
The use of potassium containing salt substitutes or a high intake of potassium rich foods may lead to significant increases in serum potassium.

May cause dizziness or fatigue, patients should not drive or operate machinery if they experience these effects.

Elderly (see Dosage Elderly ).

Can cause a positive anti doping test in athletes.

Contains lactose therefore caution should be observed in patients with glucose-galactose malabsorption syndrome and lactose intolerance.

Use with caution in patients with a family history of long QT syndrome and patients with a history of torsade de pointes. Consider monitoring ECG in patients at risk of QT prolongation. Correct electrolyte disorders before treatment.

Pregnancy and Lactation

Pregnancy

Bumetanide and amiloride tablets are contraindicated in pregnancy.

Diuretics are no longer part of the standard therapy for hypertension and oedema during pregnancy.

Diuretics can reduce the plasma volume and lead to a reduced perfusion of the placenta.

A study on 44 newborns exposed to bumetanide during the first trimester showed 2 major cardiovascular defects when 0.4 were expected. Caution should therefore especially be applied in this trimester.

Tests with bumetanide on rats, rabbits, mice and hamsters have shown a low teratogenic risk. Rabbits given doses of 3.4 times the maximum human therapeutic dose (MTHD) showed slightly embryocidal effects (Briggs, 2008).

There is inadequate human data on the use of amiloride in pregnancy but animal data comprising of its usage on mice and rabbits suggests low risk.

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 14-17 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

Contraindicated during breastfeeding. Safety has not been established.

Diuretics are thought to suppress lactation and it is not known whether the drugs are excreted to the breast milk, so the manufacturer advises avoidance if possible. Low doses in mothers whose lactation is well established are unlikely to suppress lactation.

Schaefer (2007) concludes that single doses of bumetanide do not require limitation of breastfeeding, but therapy should be changed. There is insufficient data available on amiloride.

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

Licensed in neonates - No.

Presentation

Tablets containing amiloride hydrochloride 5 mg and bumetanide 1 mg

Drugs List

amiloride 5mg and bumetanide 1mg tablets

Therapeutic Indications

Uses

When a prompt diuresis is required. Especially when potassium conservation is important.

Dosage

Adults

1 to 2 tablets daily. Adjust dose according to response.

Elderly

Adjust according to needs. Carefully monitor serum electrolytes and urea.

Children

Not recommended for use in children under 18 years old.

Patients with Renal Impairment

Avoid in severe renal impairment.

Patients with Hepatic Impairment

Amiloride and bumetanide are contraindicated in severe hepatic disease, hepatic coma and precomatose states associated with cirrhosis.

Caution is advised in mild hepatic impairment due to a possible increased risk of encephalopathy.

Contraindications

Anuria
Hyperkalaemia (serum potassium greater than 5.3 mmol / litre)
Adrenocortical impairment
Severe hepatic disease
Acute renal insufficiency
Hepatic coma
Pre-coma associated with liver cirrhosis
Severe renal impairment
Renal impairment due to hepatotoxic drugs
Renal impairment due to nephrotoxic drugs
Acute renal insufficiency
Severe electrolyte imbalance
Children under 18 years old
Breastfeeding ( see Lactation section)
Pregnancy ( see Pregnancy section)
Galactosaemia
Raised blood urea
Oliguria
Hypovolaemia
Hypotension
Severe hypokalaemia
Severe hyponatraemia
Long QT syndrome
Torsade de pointes