4.8       Undesirable Effects

The following CIOMS V convention is used: (very common (>1/10), common (1/10 – 1/100), uncommon (1/100 – 1/1000), rare (1/1000 – 1/10000), very rare (<1/10000), Not Known.

Blood and the lymphatic system disorders:

Rare:  thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia, eosinophilia, haemoconcentration.

Immune system disorders:

Rare:  severe anaphylactic or anaphylactoid reaction, anaphylactic shock. (e.g with shock)

Not Known: exacerbation or activation of systemic lupus erythematosus

Metabolism and nutrition disorders: (see section 4.4):

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 amiloride), especially in patients with impairment of renal function.

Common:  hypokalaemia, gout attack.

Rare:  hyponatremia, urine volume increased, hyperkalemia (especially in patients with impairment of renal function), blood creatinine increased, blood cholesterol increased, blood triglycerides increased, blood uric acid increased, electrolyte imbalance disturbances (including symptomatic), metabolic alkalosis due to furosemide, dehydration/hypovolemia (especially in elderly patients), hypochloremia, hypocalcemia, hypomagnesemia, blood urea increased, glucose tolerance impaired (latent diabetes mellitus may become manifest-see section 4.5), Pseudo-Bartter syndrome.

Not known:  metabolic acidosis due to amiloride,

Nervous system disorders:

Rare: paraesthesia, hepatic encephalopathy. in patients with hepatocellular insufficiency (see section 4,3).

Not Known: Dizziness, fainting or loss of consciousness, headache.

Ear and labyrinth disorders:

Rare: hearing impaired disorders (usually transitory, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephrotic syndrome) and/or when intravenous furosemide has been given too rapidly, tinnitus, deafness.

Uncommon: deafness (sometimes irreversible)

Vascular disorders:

Common: thrombosis.

Rare:  hypotension including orthostatic hypotension (see section 4.4), vasculitis.

Gastrointestinal disorders:

Very common:  nausea.

Uncommon:  vomiting, diarrhoea.

Rare: pancreatitis acute.

Hepato-biliary disorders:

Rare: cholestasis, transaminases increased.

Skin and subcutaneous tissue disorders:

Common: rash.

Rare:  pruritus, urticaria, dermatitis bullous, erythema multiforme, bullous pemphigoid, dermatitis exfloliative, purpura, photosensitivity reaction. Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, photosensitivity, acute generalised exanthematous pustulosis,  DRESS (drug rash with eosinophilia and systemic symptoms.)

Not Known: acute generalised exanthematous pustulosis (AGEP),, rashes, lichenoid reactions

Renal and urinary disorders:

Common:  urinary urine retention (acute retention of urine in patients with a partial obstruction of urinary outflow see section 4.4).

Rare:  tubulointerstitial nephritis, nephrocalcinosis, nephrolithiasis (in premature infants).

Not Known: Urine volume increased, urine sodium increased, urine chloride increase, renal failure (see section 4.5)

General disorders and administration site conditions:

Rare: fever.

Musculoskeletal and connective tissue disorders

Not Known: cases of rhabdomyolysis have been reported, often in the context of severe hypokalaemia (see section 4.3)

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9       Overdosage

Section 4.8

Common: rash.

Rare:  pruritus, urticaria, dermatitis bullous, erythema multiforme, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, photosensitivity, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms.

Not Known: acute generalised exanthematous pustulosis (AGEP) , lichenoid reactions

Skin and subcutaneous tissue disorders:

Common: rash.

Rare:  pruritus, urticaria, dermatitis bullous, erythema multiforme, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, photosensitivity, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms.

Not Known: acute generalised exanthematous pustulosis (AGEP)

Renal and urinary disorders:

Common:  urinary retention (acute retention of urine in patients with a partial obstruction of urinary outflow).

Rare:  tubulointerstitial nephritis, nephrocalcinosis, nephrolithiasis (in premature infants).

General disorders and administration site conditions:

Rare: fever.

Musculoskeletal and connective tissue disorders

Not known: cases of rhabdomyolysis have been reported, often in the context of severe hypokalaemia (see section 4.3)

Type II.C.I.4 variation to update section 4.8 of the Summary of Product Characteristics in line with the Company Core Safety Data, version 7, for Furosemide, following a Global Labelling Review.