Amiloride

When combined with thiazide diuretics, amiloride can act synergistically with chlorpropamide to increase the risk of hyponatraemia.

When amiloride is administered concomitantly with an angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist, trilostrane, ciclosporin or tacrolimus, the risk of hyperkalaemia may be increased.

Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

The concomitant administration of Amiloride and NSAIDs may lead to an increased risk of nephrotoxicity, an antagonism of the diuretic effect and possibly an increased risk of hyperkalaemia, particularly in elderly patients. Therefore, when amiloride hydrochloride is used concomitantly with NSAIDs, renal function and serum potassium levels should be carefully monitored.

To minimise the risk of hyperkalaemia in known or suspected diabetic patients, the status of renal function should be determined before initiating therapy. Amiloride hydrochloride should be discontinued for at least three days before a glucose-tolerance test.

Potassium-conserving therapy should be initiated only with caution in severely ill patients in whom metabolic or respiratory acidosis may occur e.g. patients with cardiopulmonary disease or decompensated diabetes. Shifts in acidbase balance alter the balance of extracellular-intracellular potassium, and the development of acidosis may be associated with rapid increases in plasma potassium.

Because clinical experience is limited, amiloride is not recommended for use during pregnancy. The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not indicated because they may be associated with hypovolaemia, increased blood viscosity and decreased placental perfusion.

Foetal and neonatal jaundice, foetal bone marrow depression and thrombocytopenia have also been described. The potential benefits of the drug must be weighed against the possible hazards to the foetus if it is administered to a woman of child bearing age.

It is not known whether amiloride is excreted in human milk. Because many drugs are excreted by this route, and because there is a risk that it might take this route of excretion and that it might then cause serious side effects in the breast feeding infant, the mother should either stop breast feeding or stop taking the drug. The decision depends on the importance of the drug to the mother.

None known.

Amiloride is normally well tolerated, although minor side effects are reported relatively frequently. Except for hyperkalaemia, significant side effects are infrequent. Nausea, anorexia, abdominal pain, flatulence and mild skin rash are probably due to amiloride; but other side effects are generally associated with diuresis or with the underlying condition being treated.

Body as a whole: Headache, weakness, fatigue, back pain, chest pain, neck/shoulder ache, pain in the extremities.

Cardiovascular: Angina pectoris, orthostatic hypotension, arrhythmias, palpitation, one patient with partial heart block developed complete heartblock.

Digestive: Anorexia, nausea, vomiting, diarrhoea, constipation, abdominal pain, GI bleeding, jaundice, thirst, dyspepsia, flatulence.

Metabolism and nutrition disorders: Elevated plasma potassium levels above 5.5mmol/l, hyponatraemia. Serum uric acid levels may rise during treatment with Amiloride and acute attacks of gout may be precipitated.

Integumentary: Pruritus, rash, dryness of mouth, alopecia.

Musculoskeletal: Muscle cramps, joint pain. Serum uric acid levels may rise during treatment with Amiloride and acute attacks of gout may be precipitated.

Nervous: Dizziness, vertigo, paraesthesiae, tremors, encephalopathy.

Psychiatric: Nervousness, mental confusion, insomnia, decreased libido, depression, somnolence.

Respiratory: Cough, dyspnoea.

Special Senses: Nasal congestion, visual disturbances, increased intra-ocular pressure, tinnitus.

Urogenital: Impotence, polyuria, dysuria, bladder spasm, frequency of micturition.

Reactions in which no causal relationship could be established were activation of probable pre-existing peptic ulcer, aplastic anaemia, neutropenia and abnormal liver function tests. In a few cirrhotic patients, jaundice associated with the underlying disease had deepened but the drug relationship is uncertain.