CO-AMILOFRUSE

Posology The starting dose is usually 5/40mg, subsequent dosage being adjusted to suit the needs of the patient.

Adults:

The normal dose is one to two tablets a day, to be taken in the morning. This can be increased to four tablets daily, if necessary.

Elderly:

The dose may require adjustment according to the patient’s diuretic response. Serum electrolytes and urea should be monitored carefully. Paediatric population Not recommended for use in children or adolescents under 18 years of age as safety and efficacy have not been established.

Method of administration Oral administration.

Adverse effects have been ranked under heading of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Co-amilofruse Tablets are generally well tolerated.

Blood and lymphatic system disorders Frequency not known:

Eosinophilia. Occasionally, thrombocytopenia may occur. In rare cases, leucopenia and, in isolated cases, agranulocytosis, aplastic anaemia or haemolytic anaemia may develop. Bone marrow depression has been reported as a rare complication and necessitates withdrawal of treatment.

Severe fluid depletion may lead to haemoconcentration with a tendency for thrombosis to develop.

Nervous system disorders Frequency not known:

Paraesthesia may occur. 3). Dizziness, fainting, loss of consciousness and headache.

Metabolism and nutrition disorders Frequency not known:

Serum calcium levels may be reduced; in very rare cases tetany has been observed. Blood cholesterol and blood triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months.

Glucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control; latent diabetes mellitus may become manifest. As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy.

Furosemide leads to increased excretion of sodium and chloride and consequently water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased. The serum potassium concentration may decrease, especially at the commencement of treatment owing to the earlier onset action of furosemide.

However, as treatment is continued, the serum potassium concentration may increase due to the later onset of action of amiloride, especially in patients with impaired renal function. g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses, although amiloride may contribute to the development or aggravation of metabolic acidosis.

Warning signs of electrolyte disturbances include increased thirst, headache, hypotension, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm and gastrointestinal symptoms. Disturbances of electrolyte balance, particularly if pronounced, must be corrected.

g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment. Pseudo-Bartter syndrome may occur in the context of misuse and/or long-term use of furosemide. The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in elderly patients.

As with other diuretics, treatment with furosemide may lead to transitory increases in blood creatinine and blood uric acid, hyponatraemia, hypochloraemia, hypokalaemia, attacks of gout, hypocalcaemia, hypomagnesaemia and increased blood urea.

g. in nephritic syndrome) and/or when intravenous furosemide has been given too rapidly.

Frequency uncommon:

Cases of deafness, sometimes irreversible, have been reported after administration of furosemide.

Vascular disorders Frequency not known:

Furosemide may cause a reduction in blood pressure (hypotension) which, if pronounced may cause signs and symptoms such as impairment of concentration and reactions, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance.

Thrombosis. Vasculitis.

Hepatobiliary disorders Frequency not known:

In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.

Skin and subcutaneous tissue disorders Frequency not known:

The incidence of allergic reactions, such as skin rashes, photosensitivity, vasculitis, fever, interstitial nephritis, or shock is very low, but when these occur treatment should be withdrawn. g. itching (pruritus), urticaria, other rashes or dermatitis bullous lesions, erythema multiforme, bullous pemphigoid, Stevens- Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, AGEP (acute generalised exanthematous pustulosis), DRESS (drug rash with eosinophilia and systemic symptoms) and lichenoid reactions.

Psychiatric disorders Frequency not known:

Rare complication may include minor psychiatric disturbances.

Renal and urinary disorders Frequency not known:

Increased production of urine may provoke or aggravate complaints in patients with an obstruction of urinary outflow. Urine sodium increased, urine chloride increased, acute retention of urine with possible secondary complications may occur.

For example, in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra. Nephrocalcinosis/nephrolithiasis has been reported in premature infants. Tubulointerstitial nephritis. Renal Failure.

Reproductive system and breast disorders Frequency not known:

If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus. g. with shock) occur rarely. Exacerbation or activation of systemic lupus erythematosus.

Gastrointestinal […]

Co-amilofruse should be discontinued before a glucose tolerance test. Particularly careful monitoring is necessary in: • patients with hypotension. • patients who are at risk from a pronounced fall in blood pressure. • patients where latent diabetes may become manifest or the insulin requirements of diabetic patients may increase.

• patients with gout. • patients with hepatic cirrhosis together with impaired renal function. g. associated with nephrotic syndrome (the effect of furosemide may be weakened and its ototoxicity potentiated). Cautious dose titration is required.

• symptomatic hypotension leading to dizziness, fainting or loss of consciousness can occur in patients treated with furosemide, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.

Caution should be observed in patients liable to electrolyte deficiency. Regular monitoring of serum sodium, potassium, creatinine and glucose is generally recommended during therapy; particularly close monitoring is required in patients at high risk of developing electrolyte imbalances or in case of significant additional fluid loss.

Hypovolaemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of Co-amilofruse. 73m2 body surface area as well as in cases where Co-amilofruse is taken in combination with certain other drugs which may lead to an increase in potassium levels.

In patients who are at high risk for radiocontrast nephropathy, furosemide is not recommended to be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy. Urinary output must be secured. Patients with partial obstruction of urinary outflow, for example patients with prostatic hypertrophy or impairment of micturition have an increased risk of developing acute urinary retention and require careful monitoring.

Where indicated, steps should be taken to correct hypotension or hypovolaemia before commencing therapy. Co-amilofruse should be used with caution in elderly patients or those with potential obstruction of the urinary tract or disorders rendering electrolyte balance precarious.

Co-amilofruse contains lactose This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Important information on sodium content This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Co-amilofruse contains sunset yellow This medicine contains sunset yellow (E 110) which may cause allergic reactions. 1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.

No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co- treatment with other potent diuretics should be considered prior to the decision to use.

There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. 3). The possibility exists of exacerbation or activation of systemic lupus erythematosus.

1. Patients with hypovolaemia or dehydration (with or without accompanying hypotension). 3 mmol/litre), Addison's disease, precomatose states associated with cirrhosis, concomitant potassium supplements or potassium sparing diuretics, electrolyte imbalance and breast feeding women.

Co-amilofruse is contraindicated in children and adolescents under 18 years of age, as safety in this age group has not yet been established.