AMILORIDE ROSEMONT Oral solution Ref.[6161] Active ingredients: Amiloride

Diabetes Mellitus

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.

Metabolic or Respiratory Acidosis

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 acid-base balance alter the balance of extracellular-intracellular potassium, and the development of acidosis may be associated with rapid increases in plasma potassium.

Hyperkalaemia

This has been observed in patients receiving Amiloride Hydrochloride, alone or with other diuretics. These patients should be observed carefully for clinical, laboratory or ECG evidence of hyperkalaemia.

Some deaths have been reported in this group of patients. Hyperkalaemia has been noted particularly in the elderly and in hospital patients with hepatic cirrhosis or cardiac oedema who have known renal involvement, who were seriously ill, or were undergoing vigorous diuretic therapy.

Neither potassium-conserving agents nor a diet rich in potassium should be used with Amiloride Hydrochloride except in severe and/or refractory cases of hypokalaemia. If the combination is used, plasma potassium levels must be continuously monitored.

Impaired Renal Function

Patients with increases in blood urea over 10mmol/l, serum creatinine over 130µmol/l, or with diabetes mellitus, should not receive Amiloride Hydrochloride without careful, frequent monitoring of serum electrolytes and blood urea levels. In renal impairment, use of a potassium conserving agent may result in rapid development of hyperkalaemia.

Treatment of Hyperkalemia

If hyperkalaemia occurs, Amiloride Hydrochloride should be discontinued immediately and, if necessary, active measures taken to reduce the plasma potassium level.

Electrolyte Imbalance and Reversible Blood Urea Increases.

Hyponatraemia and hypochloraemia may occur when Amiloride Hydrochloride is used with other diuretics. Reversible increases in blood urea levels have been reported accompanying vigorous diuresis, especially when diuretics were used in seriously ill patients, such as those with hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant oedema. Careful monitoring of serum electrolytes and blood urea levels should therefore be carried out when Amiloride Hydrochloride is given with other diuretics to such patients.

Cirrhotic patients

Oral diuretic therapy is more frequently accompanied by side effects in patients with hepatic cirrhosis with or without ascites, because these patients are intolerant of acute shifts in electrolyte balance, and because they often already have hypokalaemia as a result of associated aldosteronism.

In patients with pre-existing severe liver disease, hepatic encephalopathy manifested by tremors, confusion and coma, and increased jaundice has been reported in association with diuretics, including Amiloride Hydrochloride.

Excipient Warnings

This product also contains liquid maltitol. Patients with rare hereditary problems of fructose should not take this medicine.

Methyl and propyl hydroxybenzoates are contained in this product which may cause allergic reactions (possibly delayed).

This product contains a flavouring agent which contains small amounts of ethanol, less than 100mg per 5ml.

Lithium should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity.

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

Hyponatraemia and hypochloraemia may occur when Amiloride is used with other diuretics (See Section 4.4 Special warnings and precautions for use).

When Amiloride Hydrochloride 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.

Because clinical experience is limited, Amiloride Hydrochloride 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 Hydrochloride 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 Hydrochloride 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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme. www.mhra.gov.uk/yellowcard.

None known.