Co-Amilofruse 40mg/5mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-amilofruse 40mg/5mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Furosemide BP 40mg and Amiloride Hydrochloride (anhydrous) BP 5mg
3 PHARMACEUTICAL FORM
Tablets for oral administration.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Co-amilofruse is indicated where a prompt diuresis is required. It is of particular value in conditions where potassium conservation is important: congestive cardiac failure, nephrosis, corticosteroid therapy oestrogen therapy, ascites associated with cirrhosis.
4.2 Posology and method of administration
Adults
One to two tablets taken in the morning.
Elderly
The dosage should be adjusted according to diuretic response: serum electrolytes and urea should be carefully monitored.
Children
Not recommended
Route of administration
Oral
4.3 Contraindications
Hyperkalaemia (serum potassium >5.3 mmol/litre), Addison’s disease, acute renal failure, anuria, severe progressive renal disease, electrolyte imbalance, precomatose states associated with cirrhosis, concomitant potassium supplements, known sensitivity to furosemide or amiloride.
4.4 Special warnings and precautions for use
Patients who are being treated with this preparation require regular supervision, with monitoring of fluid and electrolyte states to avoid excessive loss of fluid.
Co-amilofruse should be used with particular caution in elderly patients or those with potential obstruction of the urinary tract or disorders rendering electrolyte balance precarious.
Hyponatraemia, hypochloraemia and raised blood urea nitrogen may occur during vigorous diuresis, especially in seriously ill patients. Careful monitoring of serum electrolytes and urea should therefore be undertaken in these patients.
The dosage of concurrently administered cardiac glycosides or antihypertensive agents may require adjustment.
Co-amilofruse should be discontinued before a glucose tolerance test.
Lactose warning
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
ACE inhibitors should be avoided in patients receiving Co-amilofruse as serum potassium levels may be increased. If concomitant use of ACE inhibitors is considered essential, serum electrolytes and clinical condition must be monitored carefully. Concomitant administration of potassium supplements may cause severe hyperkalaemia and is contra-indicated.
Nephrotoxicity caused by cephalosporins may be increased by concomitant administration of Co-amilofruse.
In common with other diuretics, serum lithium levels may be increased when lithium is given concomitantly with furosemide, necessitating adjustment of the lithium dosage.
Certain non-steroidal anti-inflammatory agents (e.g. indomethacin) may attenuate the action of furosemide and may cause renal failure in cases of preexisting hypovolaemia.
The effects of curariform muscle relaxants may be enhanced by furosemide, whilst the effects of antidiabetics may be reduced.
The diuretic effects of furosemide may be reduced by concurrent administration of phenytoin.
Interactions have also been reported with ototoxic antibiotics. In cases of concomitant glucocorticoid therapy or abuse of laxatives, the risk of an increased potassium loss should be borne in mind.
4.6 Pregnancy and lactation
The safety of co-amilofruse has not been established during pregnancy and lactation.
4.7 Effects on ability to drive and use machines
Reduced mental alertness may impair ability to drive or operate dangerous machinery.
4.8 Undesirable effects
As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy. This may cause symptoms such as headache, hypotension and muscle cramps.
Hyperkalaemia has been observed in patients receiving amiloride hydrochloride.
Furosemide may cause latent diabetes to become manifest. It may be necessary to increase the dose of hypoglycaemic agents in diabetic patients.
Patients with prostatic hypertrophy or impairment of micturition have an increased risk of developing acute urinary retention during diuretic therapy.
Serum uric acid levels may rise during treatment with co-amilofruse and acute attacks of gout may be precipitated.
Malaise, gastric upset, nausea, vomiting, diarrhoea, and constipation may occur.
If skin rashes or pruritus occur, treatment should be withdrawn.
Rare complications may include minor psychiatric disturbances, disturbances in liver function tests and ototoxicity.
Bone marrow depression occasionally complicates treatment, necessitating withdrawal of the product.
The haematopoietic state should be regularly monitored during treatment
Serum calcium levels may be reduced; in very rare cases tetany has been observed.
Serum cholesterol and triglyceride levels may rise during furosemide treatment but usually return to normal within six months during long term therapy.
4.9 Overdose
Treatment of overdosage should be aimed at reversing dehydration and correcting electrolyte imbalance, particularly hyperkalaemia. Emesis should be induced or gastric lavage performed. Treatment is symptomatic and supportive. If hyperkalaemia is seen, appropriate measures to reduce serum potassium must be instituted.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Amiloride
Amiloride is a mild diuretic which appears to act mainly on the distal renal tubules. It is described as potassium-sparing since, like spironolactone, it increases the excretion of sodium and chloride and reduces the excretion of potassium. Unlike spironolactone, however, it does not act by inhibiting aldosterone. Amiloride does not inhibit carbonic anhydrase. It takes effect about 2 hours after administration by mouth and its diuretic action has been reported to persist for about 24 hours. The full effect may be delayed until after several days of treatment.
Furosemide
Furosemide is a potent diuretic with a rapid action. Its effects are evident within 30 minutes to 1 hour after a dose by mouth and lasts for about 4 to 6 hours. After intravenous injection its effects are evident in about 5 minutes and last for about 2 hours. Furosemide inhibits the reabsorption of electrolytes in the ascending limb of the loop of Henle and also in the distal renal tubules. It may also have a direct effect in the proximal tubules. Excretion of sodium, potassium, and chloride ions is increased and water excretion enhanced. It has no clinically significant effect on carbonic anhydrase.
5.2 Pharmacokinetic properties
Amiloride is incompletely absorbed from the gastro-intestinal tract; bioavailability of about 50% is reported and is reduced by food. It is not bound to plasma proteins and has a half-life of 6 to 9 hours. It is excreted unchanged by the kidneys.
Furosemide
Furosemide is incompletely but fairly rapidly absorbed from the gastrointestinal tract,; bioavailability has been reported to be about 60 to 70% but is reduced in renal failure. It has a biphasic half-life in the plasma with a terminal elimination phase that has been estimated to range up to about 1/ hours although it is prolonged in renal and hepatic insufficiency. It is up to 99% bound to plasma proteins, and is mainly excreted in the bile, non-renal elimination being considerably increased in renal failure. Furosemide crosses the placental barrier and is excreted in milk.
5.3 Preclinical safety data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose BP,
Starch BP,
Anstead dispersed orange 11348 (E11, Starch (pre-gelatinised) BP Croscarmellose sodium USP, Magnesium stearate BP,
Talc BP
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store in a dry place below 25°C and protect from light.
6.5 Nature and contents of container
Polypropylene tubular container with an open end equipped to accept a polyethylene closure with a tamper-evident tear strip, tampertainers or duma containers. Pack sizes 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 500 and 1000 tablets.
250 pm opaque UPVC/20 pm hard temper aluminium foil strip packs or PVdC coated PVC/Aluminium blisters (60g/m2 PVdC on 250pm PVC/20pm Al) containing 7, 14, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112 and 120 tablets.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Teva UK Limited Brampton Road Hampden Park Eastbourne East Sussex BN22 9AG
8 MARKETING AUTHORISATION NUMBER(S)
PL 00289/1633
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06 March 1991 / 24 June 1997
10 DATE OF REVISION OF THE TEXT
12/10/2012