|Frequencies for the following adverse reactions are not known (cannot be estimated from available data):Furosemide is generally well tolerated.Blood and lymphatic system disordersBone marrow depression has been reported as a rare complication and necessitates withdrawal of treatment.Occasionally, thrombocytopenia may occur. In rare cases, leucopenia and, in isolated cases, agranulocytosis, aplastic anaemia or haemolytic anaemia may develop. Eosinophilia is rare.|
Nervous system disordersRarely, paraesthesiae may occur.Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see Section 4.3).
Renal and urinary disordersSerum calcium levels may be reduced; in very rare cases tetany has been observed. Nephrocalcinosis / Nephrolithiasis has been reported in premature infants.Increased production of urine may provoke or aggravate complaints in patients with an obstruction of urinary outflow. Thus, 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.
Ear and labyrinth disordersHearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephrotic syndrome) and/or when intravenous furosemide has been given too rapidly. Cases of deafness, sometimes irreversible have been reported after oral or IV administration of furosemide.
Vascular disordersFurosemide may cause a reduction in blood pressure 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.
Hepato-biliary disordersIn isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.
Skin and subcutaneous tissue disordersThe incidence of allergic reactions, such as skin rashes, photosensitivity, vasculitis, fever or interstitial nephritis, is very low, but when these occur treatment should be withdrawn. Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, erythema multiforme, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, AGEP (acute generalized exanthematous pustulosis) and DRESS (Drug rash with eosinophilia and systemic symptoms).
Metabolism and nutrition disordersAs 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, calcium and magnesium) is increased. The two active ingredients exert opposing influences on potassium excretion. The serum potassium concentration may decrease, especially at the commencement of treatment (owing to the earlier onset of action of furosemide), although particularly as treatment is continued, the potassium concentration may increase (owing to the later onset of action of spironolactone), especially in patients with renal failure.Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or, e.g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses. Warning signs of electrolyte disturbances include increased thirst, headache, hypotension, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm and gastrointestinal symptoms. In the event of an irregular pulse, tiredness or muscle weakness (e.g., in the legs), particular consideration must be given to the possibility of hyperkalaemia. Pre-existing metabolic alkalosis (e.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.Disturbances in electrolyte balance, particularly if pronounced, must be corrected.The diuretic action may lead to or contribute to hypovolaemia and dehydration, especially in elderly patients. To avert these, it is important to compensate any undesired losses of fluid (e.g., due to vomiting or diarrhoea, or to intense sweating). Severe fluid depletion may lead to haemoconcentration with a tendency for thromboses to develop.Serum cholesterol and 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, treatment with furosemide may lead to transitory increases in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.
Immune system disordersSevere anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.
Gastro-intestinal disordersSide-effects of a minor nature such as nausea, malaise or gastric upset (vomiting or diarrhoea) may occur but are not usually severe enough to necessitate withdrawal of treatment.Spironolactone has been reported to induce gastrointestinal intolerance. Stomach ulcers (sometimes with bleeding) have been reported rarely. Spironolactone may also cause drowsiness, headache, ataxia and mental confusion.
Reproductive system and breast disordersBecause of its chemical similarity to the sex hormones, spironolactone may make the nipples more sensitive to touch. Dose dependent mastodynia and reversible gynaecomastia may occur in both sexes. Maculopapular or erythematous cutaneous eruptions have been reported rarely, as have mild androgenic manifestation such as hirsutism and menstrual irregularities. In men, potency may occasionally be impaired. If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.
Respiration, thoracic and mediastinal disordersRarely, spironolactone may cause vocal changes in the form of hoarseness and (in women), deepening of the voice or (in men) increase in pitch. In some patients these vocal changes persist even after Lasilactone has been discontinued.
Reporting of suspected adverse reactionsReporting 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard