DIAMOX Sodium Powder for solution for injection Ref.[6055] Active ingredients: Acetazolamide

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for DIAMOX injection.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paraesthesia.

Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.

When DIAMOX injection is prescribed for long-term therapy, special precautions are advisable. The patient should be cautioned to report any unusual skin rash.

Periodic blood cell counts and electrolyte levels are recommended. Fatalities have occurred, although rarely, due to severe reactions to sulphonamides. A precipitous drop in formed blood cell elements or the appearance of toxic skin manifestations should call for immediate cessation of DIAMOX injection therapy.

In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, DIAMOX injection which may aggravate acidosis, should be used with caution.

In patients with a past history of renal calculi, benefit should be balanced against the risks of precipitating further calculi.

The pH of parenteral acetazolamide is 9.1. Care should be taken during intravenous administration of alkaline preparations to avoid extravasation and possible development of skin necrosis

The occurrence at the treatment initiation of a feverish generalized erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP) (See section 4.8). In case of AGEP diagnosis, acetazolamide should be discontinued and any subsequent administration of acetazolamide contraindicated.

Acetazolamide is a sulphonamide derivative. Sulphonamides may potentiate the effects of folic acid antagonists. Possible potentiation of the effects of folic acid antagonists, hypoglycaemics and oral anti-coagulants. Concurrent administration of acetazolamide and aspirin may result in severe acidosis and increase central nervous system toxicity. Adjustments of dose may be required when DIAMOX injection is given with cardiac glycosides or hypertensive agents.

When given concomitantly Acetazolamide modifies the metabolism of phenytoin leading to increased serum levels of phenytoin. Severe osteomalacia has been noted in a few patients taking acetazolamide in combination with other anticonvulsants. There have been isolated reports of reduced primidone and increased carbamazepine serum levels with concurrent administration of acetazolamide.

Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable.

Acetazolamide has been reported to be teratogenic and embryotoxic in rats, mice, hamsters and rabbits at oral or parenteral doses in excess of ten times those recommended in human beings. Although there is no evidence of these effects in human beings, there are no adequate and well-controlled studies in pregnant women. Therefore, DIAMOX injection should not be used in pregnancy, especially during the first trimester.

Acetazolamide has been detected in low levels in the milk of lactating women who have taken DIAMOX injection. Although it is unlikely that this will lead to any harmful effects in the infant, extreme caution should be exercised when DIAMOX injection is administered to lactating women.

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paraesthesia. Less commonly, fatigue, dizziness and ataxia have been reported. Disorientation has been observed in a few patients with oedema due to hepatic cirrhosis. Such cases should be under close supervision. Transient myopia has been reported.

These conditions invariably subside upon diminution or discontinuance of the medication.

Adverse reactions during short-term therapy are usually non-serious. Those effects which have been noted include: paraesthesia, particularly a tingling feeling in the extremities, some loss of appetite; taste disturbance, polyuria, flushing, thirst, headache, dizziness, fatigue, irritability, depression, reduced libido and occasional instances of drowsiness and confusion. Rarely, photosensitivity has been reported.

During long-term therapy, metabolic acidosis and electrolyte imbalance may occasionally occur. This can usually be corrected by the administration of bicarbonate.

Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuation of the medication.

Gastro-intestinal disturbances such as nausea, vomiting and diarrhoea.

Acetazolamide is a sulphonamide derivative and therefore some side effects similar to those caused by sulphonamides have occasionally been reported. These include fever, agranulocytosis, thrombocytopenia, thrombocytic purpura, leukopenia and aplastic anaemia, bone marrow depression, pancytopenia, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), anaphylaxis, crystalluria, calculus formation, renal and ureteral colic and renal lesions. Rarely, fulminant hepatic necrosis has been reported.

Other occasional adverse reactions include: urticaria, melaena, haematuria, glycosuria, impaired hearing and tinnitus, abnormal liver function, renal failure and, rarely, hepatitis or cholestatic jaundice, flaccid paralysis and convulsions.

Skin and subcutaneous tissue disorders

Not known: acute generalised exanthematous pustulosis (AGEP)

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

None.