DIAMOX SR Capsule Ref.[6056] Active ingredients: Acetazolamide

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

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.

When acetazolamide is prescribed for long-term therapy, special precautions are advisable. The patient should be cautioned to report any unusual skin rash. Prior to initiating therapy and at regular intervals during therapy monitoring of blood cell counts and electrolyte levels are recommended. Fatalities have occurred, although rarely, due to severe reactions to sulphonamides including acetazolamide, such as Steven-Johnson syndrome and toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias and anaphylaxis. A precipitous drop in formed blood cell elements or the appearance of toxic skin manifestations should call for immediate cessation of acetazolamide therapy.

Hypersensitivity reactions may recur if a sulphonamide or sulphonamide derivative is re-administered, irrespective of the route of administration. If signs of hypersensitivity reactions or other serious reactions occur, acetazolamide must be discontinued.

Acetazolamide treatment may cause electrolyte imbalances, including hyponatraemia and transient hypokalaemia, as well as metabolic acidosis. Therefore, periodic monitoring of serum electrolytes is recommended. Particular caution is recommended in patients with conditions that are associated with, or predispose to, electrolyte and acid/base imbalances, such as patients with impaired renal function (including elderly patients), pulmonary obstruction, emphysema, patients with diabetes mellitus and patients with impaired alveolar ventilation. Severe metabolic acidosis has been reported in patients with normal renal function during treatment with acetazolamide and salicylates.

Both increased and decreases in blood glucose levels have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus.

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

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 may occur. Concurrent administration of acetazolamide and acetylsalicylic acid may result in severe toxicity and increase central nervous system toxicity. Severe metabolic acidosis has been reported in patients with normal renal function during treatment with acetazolamide and salicylates. Adjustment of dose may be required when acetazolamide 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.

Concomitant use with other carbonic anhydrase inhibitors is not advisable because of possible additive effects.

Both increases and decreases in blood glucose levels have been described in patients with acetazolamide. This should be taken into consideration in patients treated with anti-diabetic agents.

By increasing the pH of renal tubular urine, acetazolamide reduces the urinary excretion of amphetamine and quinidine and so may enhance the magnitude and duration of the effect of amphetamines and enhance the effect of quinidine.

By increasing the pH of urine, acetazolamide may prevent the urinary excretion of methenamine compounds.

Acetazolamide increases lithium excretion due to impaired re-absorption of lithium in the proximal tubule. The effect of lithium carbonate may be decreased.

The use of concurrent sodium bicarbonate therapy enhances the risk of renal calculus formation in patients taking acetazolamide.

When given concomitantly, acetazolamide may elevate cyclosporine blood levels. Caution is advised when administrating acetazolamide in patients receiving cyclosporine.

Interference with Laboratory and other Diagnostic Tests:

Acetazolamide may produce an increased level of crystals in the urine.

Acetazolamide interferes with the HPLC method of assay for theophylline. Interference with the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods for theophylline.

Use in pregnancy

Acetazolamide should not be used in pregnancy, especially during the first trimester. (See section 5.3)

Use in lactation

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

Acetazolamide has minor or moderate influence on the ability to drive and use machines.

Some adverse reactions to acetazolamide, such as drowsiness, fatigue and myopia, may impair the ability to drive and operate machinery.

Adverse reactions during short-term therapy are usually non-serious.

Those effects which have been noted include:

Blood and Lymphatic system disorder

Uncommon: Thrombocytopenia, Leukopenia, Aplastic anaemia, Bone marrow depression, Pancytopenia

Not Known: Agranulocytosis

Metabolism and Nutrition Disorders

Common: Acidosis. The acidosis can usually be corrected by the administration of bicarbonate.

Uncommon: Hypokalaemia, Metabolic acidosis

Rare: Appetite disorders Hyponatraemia, Hyperglycaemia and hypoglycaemia may occasionally occur during long term therapy.

Very rare: Electrolyte imbalance

Not known: Thirst

Psychiatric Disorders

Uncommon: Depression

Rare: Confusion

Very Rare: Irritability, reduced libido.

Nervous system disorders

Very common: Paraesthesia, Tingling of extremity

Uncommon: Dizziness

Very rare: Headache, Ataxia, Convulsions, Flaccid paralysis, Sensory disturbances

Not known: Excitement, Occasional instances of drowsiness

Eye Disorders

Not known: Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuation of the medication.

Ear and Labyrinth Disorder

Uncommon: Impaired hearing and tinnitus.

Gastrointestinal disorders

Uncommon: Melaena, Nausea, Vomiting

Rare: Diarrhoea

Not known: Taste disturbance.

Hepatobiliary disorders

Rare: Fulminant hepatic necrosis, Hepatitis or cholestatic jaundice

Skin and subcutaneous tissue disorders

Uncommon: Urticaria, Rash (including Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis

Rare: Photosensitivity

Very rare: Thrombocytic purpura

Not known: acute generalised exanthematous pustulosis (AGEP)

Musculoskeletal and connective tissue disorders

Uncommon: Osteomalacia with long-term phenytoin therapy

Renal and urinary disorders

Very common: Nephrolithiasis.

Common: Haematuria

Uncommon: Crystalluria, Renal and ureteral colic, Renal lesions, Renal failure, nephrolithiasis , Calculus formation, Haematuria

Very rare: Renal tubular necrosis

Not known: Polyuria, Ureteral pain, Glycosuria

General disorders and administration site conditions

Very rare: Flushing, Fever, Fatigue, Anaphylaxis

Investigations

Uncommon: Abnormal liver function

Injury, poisoning and procedural complications

Not known: Renal injury

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. By reporting side effects you can help provide more information on the safety of this medicine.

None.