ACETAZOLAMIDE

Posology i) Glaucoma (simple, acute congestive and secondary):

Adults: 250 - 1,000mg (1-4 tablets) per 24 hours, usually in divided doses for amounts over 250mg daily. ii) 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 Acetazolamide 250mg 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 - 375mg is suggested. iii) Epilepsy: Adults: 250 - 1,000mg daily in divided doses. Children: 8-30mg/kg in daily divided doses and not to exceed 750mg/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 For oral administration

Acetazolamide is a sulphonamide derivative and therefore some side-effects similar to those caused by sulphonamides have occasionally been reported Acetazolamide effects Sulphonamide class effects Blood & lymphatic system disorders Occasional Agranulocytosis; thrombocytopenia; thrombocytic purpura; leukopenia; aplastic anaemia; bone marrow depression; pancytopenia Immune system disorders Occasional Anaphylaxis Metabolism & nutrition disorders Common Loss of appetite; thirst; Occasional metabolic acidosis; electrolyte imbalance Psychiatric disorders Common Irritability; Uncommon depression; confusion Nervous system disorders Common Paraesthesia; headache; dizziness; Uncommon drowsiness Rare Flaccid paralysis; convulsions Eye disorders Uncommon Transient myopia Not known Choroidal effusion, choroidal detachment Ear & labyrinth disorders Uncommon Impaired hearing; tinnitus Vascular disorders Common Flushing Gastrointestinal disorders Common Taste disturbance; nausea; vomiting; diarrhoea Very rare Melaena Hepatobiliary disorders Occasional Abnormal liver function Rare hepatitis; cholestatic jaundice; Fulminant hepatic necrosis; Skin & subcutaneous tissue disorders Rare Photosensitivity; rash Occasional urticaria Rash including erythema multiforme; Stevens- Johnson syndrome; toxic epidermal necrolysis; Not known Acute generalised exanthematous pustulosis (AGEP) Renal & Urinary disorders Common Polyuria Occasional glycosuria; renal failure Crystalluria; calculus formation; renal colic; ureteral colic; renal lesions; Very rare haematuria; Reproductive system & breast disorders Uncommon Reduced libido General disorders & Administration Site conditions Common Fatigue Occasional Fever Respiratory, thoracic and mediastinal disorders Not known Non-cardiogenic pulmonary oedema

Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic 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 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 acetazolamide 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 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.

8). In case of AGEP diagnosis, acetazolamide should be discontinued and any subsequent administration of acetazolamide contraindicated. Cases of choroidal effusion/detachment have been reported after the use of acetazolamide. Symptoms include acute onset of decreased visual acuity or ocular pain and can occur within hours after initiation of acetazolamide treatment.

If choroidal effusion/detachment is suspected, acetazolamide should be discontinued as rapidly as possible. 8). Non-cardiogenic pulmonary oedema typically developed within minutes to hours after acetazolamide intake. Symptoms included dyspnoea, hypoxia, and respiratory insufficiency.

If non- cardiogenic pulmonary oedema is suspected, acetazolamide should be withdrawn, and supportive treatment should be given. Acetazolamide should not be administered to patients who previously experienced non-cardiogenic pulmonary oedema following acetazolamide intake.

Acetazolamide is contra-indicated in situations in which sodium and/or potassium blood levels are depressed, in cases of marked kidney and liver disease or dysfunction, suprarenal gland failure, and hyperchloremic acidosis. Acetazolamide 250mg tablets should not be used in patients with hepatic cirrhosis as this may increase the risk of hepatic encephalopathy.

Long-term administration of acetazolamide is contra-indicated 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 intraocular pressure.

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