Amiloride Tablets Bp 5mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Amiloride Tablets BP 5mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Amiloride Hydrochloride BP 5.70mg
(equivalent to 5.0mg anhydrous Amiloride Hydrochloride)
Also contains lactose.
For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Potassium conserving diuretic.
While Amiloride may be used independently, its main indication is for concurrent therapy with either thiazides or more potent diuretics in order to conserve potassium during episodes of vigorous diuresis and during long-term maintenance therapy.
(i) Congestive heart failure, primarily for concurrent use in patients receiving thiazides or more potent diuretic agents.
(ii) Hypertension, as an adjunctive agent.
(iii) Hepatic cirrhosis with ascites and oedema.
4.2 Posology and method of administration
Route of administration: Oral Adults:
The initial dosage should be 10mg either as a single dose or 5mg twice a day. This may be increased if necessary, but must not exceed 20mg (4 tablets) per day. After diuresis has been achieved, the dosage may be reduced to the least amount required (by 5mg increments).
Congestive heart failure:
Amiloride may be started at a dosage of 5mg (1 tablet) a day, together with the usual dosage of other diuretic agents. If diuresis is not achieved with minimal dosage of both agents, the dosage of both may be gradually increased, but that of Amiloride should not exceed 10mg (2 tablets) a day. Once diuresis has been achieved, reduction in dosage of both agents may be attempted for maintenance therapy. The dosage of both agents should be determined by the diuretic response and the plasma potassium level.
Hypertension
Amiloride is given at a dosage of 5mg or 10mg (1 or 2 tablets) a day, together with the usual antihypertensive dosage of thiazides.
Hepatic cirrhosis with ascites
Treatment should be started with a small dose of Amiloride, i.e. 5mg (1 tablet), plus a low dosage of the other diuretic agent. If necessary, dosage of both agents may be increased gradually until there is effective diuresis.
The dosage of Amiloride should not exceed 10mg (2 tablets) a day. Maintenance doses may be lower than those required to initiate diuresis; reduction in the daily dosage should therefore be attempted when the patient's weight is stabilised.
Gradual weight reduction in cirrhotic patients is especially desirable to reduce the likelihood of untoward reactions.
Elderly:
Because the elderly are more susceptible to electrolyte imbalance and because renal reserve may be reduced, they are more likely to experience hyperkalaemia. The dosage should be adjusted according to renal function, blood electrolytes and diuretic response.
Children:
The use of Amiloride is not recommended in children as safety has not been established.
4.3 Contraindications
Hypersensitivity to Amiloride Hydrochloride and to any of the excipients listed in section 6.1.
Hyperkalaemia (plasma potassium over 5.5mmol/l); other potassium-conserving agents or potassium supplements; anuria, acute renal failure, severe progressive renal disease and diabetic nephropathy.
Use in children as safety has not been established.
4.4 Special warnings and precautions for use
Diabetes Mellitus: To minimise the risk of hypokalaemia in known or suspected diabetic patients, the status of renal function should be determined before initiating therapy. Amiloride should be discontinued 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 of 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 and 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 except in severe and/or refractory cases of hypokalaemia. If the combination is used, plasma potassium levels must be continuously monitored.
Treatment of hyperkalaemia: If hyperkalaemia occurs, Amiloride should be discontinued immediately and, if necessary, active measures taken to reduce the plasma potassium level.
Concurrent administration of a potassium-sparing diuretic to a patient receiving an ACE inhibitor or an angiotensin-II receptor antagonist can cause severe hyperkalaemia.
Impaired renal function: Patients with blood urea over 10mmol/l, serum creatinine over 130pmol/l, or with diabetes mellitus require careful monitoring of serum electrolytes and blood urea levels. In renal impairment, use of a potassium-conserving agent may result in rapid development of hyperkalaemia.
Electrolyte imbalance and 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 is given with oral 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.
Reports suggest that patients with pre-existing severe liver disease treated with diuretics, including Amiloride Hydrochloride, may experience hepatic encephalopathy, manifested by tremors, confusion and coma, and increased jaundice.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorbtion should not take Amiloride Hydrochloride.
4.5 Interaction with other medicinal products and other forms of interaction
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. There is also an increased risk of hyponatraemia when diuretics are given with carbamazepine.
There is an increased risk of hyperkalaemia with cyclosporine and the hormone antagonist trilostane; likewise with potassium salts. Amiloride antagonises the ulcer healing effect of carbenoxolone.
There is a risk of decreased renal function and the development of hyperkalaemia with NSAIDs (e.g. indometacin). Concomitant use with platinum compounds may increase the risk of nephrotoxicity and ototoxicity.
When Amiloride is administered concurrently with an angiotensin-converting enzyme inhibitor, ACE inhibitors, NSAIDs,ciclosporin, drospirenone, trilostane 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. In patients receiving Amiloride with NSAIDs or ciclosporin the risk of nephrotoxcity may also be increased.
Hypokalaemia caused by diuretics increases the risk of ventricular arrhythmias with amisulpride, pimozide and sertindole.
Concurrent administration of ACE inhibitors, adrenergic neurone blockers, alcohol, aldesleukin, alpha blockers, alprostadil, general anaesthesia , angiotensin-II receptor antagonists, anxiolytics & hypnotics, baclofen, beta blockers, calcium channel blockers, clonidine, diazoxide, hydralazine, levodopa, MAOIs, methyldopa, minoxidil, moxisylyte, moxonidine, nitrates, nitroprusside, phenothiazines or tizanidine may enhance the hypotensive effect.
There is an increased risk of postural hypotension when diuretics are given with tricyclic.antidepressants,
Corticosteroids, ketorolac and oestrogens antagonise diuretic effect of diuretics.
4.6 Pregnancy and lactation
Pregnancy
Amiloride is not recommended for use during pregnancy due to limited clinical experience. The potential benefits must be weighed against possible hazards to a foetus if administered to women of child bearing age.
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 depression and thrombocytopenia have also been described.
Lactation
It is not known whether Amiloride is excreted in human milk. Therefore, due to the risk that it may take this route of excretion, and possibly cause serious adverse reactions to the nursing infant the mother should stop breast-feeding or cease taking the drug.
4.7 Effects on ability to drive and use machines
None stated
4.8 Undesirable effects
Amiloride is usually well tolerated, although minor side-effects are reported relatively frequently. Apart from hyperkalaemia, significant adverse reactions have been infrequently reported. Nausea/anorexia, abdominal pain, flatulence and mild skin rashes have been reported and are probably due to Amiloride; but other side-effects are generally associated with diuresis or with the underlying disease being treated.
Body as a whole: Headache, weakness, fatigue, back pain, chest pain, neck/shoulder ache, pain in extremities.
Cardiovascular: Angina pectoris, orthostatic hypotension, arrhythmias,
palpitation, one patient with a partial heart block developed complete heart block.
Digestive: Anorexia, nausea, vomiting, diarrhoea, constipation, abdominal pain, GI bleeding, jaundice, thirst, dyspepsia, heartburn, flatulence.
Integumentary: Pruritus, rash, dryness of mouth, alopecia
Metabolic: Elevated plasma potassium levels over 5.5 mmo1/l,
hyponatraemia.
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, paraesthesia, tremor, 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 spasms, 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 has deepened, but the drug relationship is unknown.
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 Schemeat:www.mhra.gov.uk/yellowcard
4.9 Overdose
No data are available; it is not known whether the drug is dialysable. No specific antidote is available.
The most likely signs and symptoms are dehydration and electrolyte imbalance which should be treated by established methods. Therapy should be discontinued and the patient closely observed. Emesis should be induced or gastric lavage should be performed if ingestion is recent. Treatment is symptomatic and supportive. If hyperkalaemia occurs, active measures should be taken to reduce plasma potassium levels.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Amiloride takes effect about two hours after administration by mouth and its diuretic action persists for about 24 hours. It acts mainly on the distal renal tubules. It increases the excretion of sodium and chloride and reduces the excretion of potassium.
Amiloride enhances the natiuretic and diminishes the kaliuretic effects of other diuretics.
5.2 Pharmacokinetic properties
Amiloride is completely absorbed from the gastro-intestinal tract. Biological half-life in the circulation is about six hours. It is excreted unchanged in the urine.
Peak serum concentrations are reached in about four hours after a dose. About half of a dose is excreted unchanged in the urine within 72 hours.
Preclinical safety data
5.3
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose BP
Calcium hydrogen phosphate BP Pregelatinised maize starch BP Maize starch BP Magnesium stearate BP Purified water BP
6.2 Incompatibilities
None stated.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Store below 25 °C in a dry place in well closed containers. Protect from light.
6.5 Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers with polypropylene or polythene lids and polyurethane polythene inserts.
Pack sizes: 100 and 500
Blister pack:
20 micron hard-tempered aluminium foil, coated on the dull side with 6-7 GSM heat-seal lacquer and printed on the bright side; 250micron rigid, green PVC Pharmaceutical Grade.
Pack sizes: 28 and 84
(1 x 28 tablets Calendar Pack in a carton 3 x 28 tablets Calendar Packs in a carton)
6.6 Special precautions for disposal
No special requirements for disposal>
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Mercury Pharmaceuticals Ltd Capital House,
85 King William Street,
London EC4N 7BL UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 12762/0419
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/11/1997
10 DATE OF REVISION OF THE TEXT
10/04/2015