ACETAZOLAMIDE

Posology 1. Glaucoma (simple acute congestive and secondary) Adults: 250 - 1,000mg (1 – 4 tablets) per 24 hours, usually in divided doses for amounts over 250 mg daily. 2. Abnormal retention of fluid (congestive heart failure, drug-induced oedema) Adults: For diuresis, the starting dose is usually 250 - 375mg (1 – 1½ tablets) once daily in the morning.

If after an initial response, the patient fails to continue to lose oedema fluid, do not increase the dose but allow for kidney recovery by omitting a day. Best results are often obtained on a regime of 250 - 375mg (1 – 1½ tablets) daily for two days, rest a day and repeat, or merely giving the tablets every other day.

g. digitalis, bed rest and salt restriction in congestive heart failure and proper supplementation with elements such as potassium in drug-induced oedema. For cases of fluid retention associated with pre-menstrual tension, a daily dose (single) of 125 – 375 mg is suggested.

3. Epilepsy Adults: 250 – 1000 mg daily in divided doses. Children: 8 – 30 mg/kg body-weight in daily divided doses, and not to exceed 750 mg/day. The change from other medication to acetazolamide should be gradual.

Elderly:

Acetazolamide should only be used with particular caution in elderly patients or those with potential obstruction in the urinary tract or with disorders rendering their electrolyte balance precarious or with liver dysfunction.

Method of administration:

Oral

The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: Not known: frequency cannot be estimated from the available data System organ class Frequency Adverse reactions Blood and lymphatic system disorders Not known Thrombocytopenia, leukopenia, aplastic anaemia, bone marrow depression, pancytopenia, agranulocytosis**** Metabolism and nutrition disorder Not known Metabolic acidosis, electrolyte imbalance* and thirst** Psychiatric disorders Not known Depression, irritability, reduced libido, Occasional instances of confusion Nervous system disorders Not known Paraesthesia, particularly a “tingling” feeling in the extremities, dizziness, headache, occasional instances of drowsiness, convulsions, flaccid paralysis Eye disorders Not known Transient myopia*** , Choroidal effusion, choroidal detachment Ear and labyrinth disorders Not known Impaired hearing and tinnitus Gastrointestinal disorders Not known Melaena, taste disturbance, nausea, vomiting, diarrhoea Hepatobiliary disorders Not known Fulminant hepatic necrosis****, hepatitis or cholestatic jaundice Skin and subcutaneous tissue disorders Not known Urticaria, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)****, thrombocytic purpura, photosensitivity, acute generalised exanthematous pustulosis (AGEP) Renal and urinary disorders Not known Haematuria, crystalluria****, renal and ureteral colic****, renal lesions, renal failure, calculus formation****, glycosuria, polyuria General disorders and administration site conditions Not known Fever****, fatigue, anaphylaxis****, flushing Investigations Not known Abnormal liver function Respiratory, thoracic and mediastinal disorders Not known Non-cardiogenic pulmonary oedema *During long-term therapy, metabolic acidosis and electrolyte imbalance may occasionally occur.

This can usually be corrected by the administration of bicarbonate. **Adverse reactions during short-term therapy are usually non-serious. ***This condition invariably subsides upon diminution or withdrawal of the medication. ****Acetazolamide is a sulfonamide derivative and therefore some side- effects similar to those caused by sulfonamides have occasionally been reported.

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 acetazolamide. 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 acetazolamide 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 acetazolamide is prescribed for long-term therapy, special precautions are advisable.

The patient should be cautioned to report any unusual skin rash. 8). In case of AGEP diagnosis, acetazolamide should be discontinued and any subsequent administration of acetazolamide contraindicated. Periodic monitoring of blood cell counts and electrolyte levels are recommended.

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides. A precipitous drop in formed blood cell elements or the appearance of toxic skin manifestations should call for immediate cessation of acetazolamide therapy.

In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide may aggravate acidosis and 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.

1. Depressed sodium and/or potassium blood serum levels. Marked kidney and liver disease or dysfunction. Suprarenal gland failure, and hyperchloremic acidosis. Should not be used in patients with hepatic cirrhosis as this may increase the risk of hepatic encephalopathy.

Long term administration is contraindicated in patients with chronic non- congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intra- ocular pressure.