Acetazolamide Tablets 250mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
ZOLAMOX - Acetazolamide Tablets 250mg BP.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Acetazolamide BP 250.00 mg
Excipients with known effect: Each tablet also contains 150 mg of lactose For full list of excipients see section 6.1
3 PHARMACEUTICAL FORM
Tablets
Round, odourless, white biconvex uncoated tablets with crossed score-lines on one side and plain on the other side
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Acetazolamide is an enzyme inhibitor which acts specifically on carbonic anhydrase.
It is indicated in the treatment of:
- Glaucoma: Acetazolamide Tablets is useful in glaucoma (chronic simple (open angle) glaucoma, secondary glaucoma, and perioperatively in acute angle closure glaucoma where delay of surgery is desired in order to lower intraocular pressure) because it acts on inflow, decreasing the amount of aqueous secretion.
- Abnormal retention of fluids: Acetazolamide Tablets is a diuretic whose effect is due to the effect on the reversible hydration of carbon dioxide and dehydration of carbonic acid reaction in the kidney. The result is renal loss of HC03- ion which carries out sodium, water and potassium. Acetazolamide Tablets can be used in conjunction with other diuretics when effects on several segments of the nepbron are desirable in the treatment of fluid retaining states.
- Epilepsy: In conjunction with other anticonvulsants best results with Acetazolamide Tablets have been seen in petit mal in children. Good results, however, have been seen in patients, both children and adults, with other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns etc.
4.2 Posology and method of administration
Route of administration - Oral
Abnormal retention of fluid: Congestive heart failure, drug-induced oedema.
Adults: For diuresis, the starting dose is usually 1-1/ tablets (250-375 mg) 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 treatment for a day. Best results are often obtained on a regime of 250 - 375 mg (1-1/ tablets) daily for two days, missing a day, and then repeating or merely giving the acetazolamide every other day. The use of acetazolamide does not eliminate the need for other therapy, e.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.
Epilepsy:
Adults: 250 mg-1000 mg 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.
Glaucoma (simple acute congestive and secondary):
Adults: 250-1000 mg (1-4 tablets) in a 24 hour period, usually in divided doses for amounts over 250 mg daily.
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.
4.3 Contraindications
Acetazolamide should not be used in patients hypersensitive to sulphonamides.
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 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.
Hypersensitivity to Acetazolamide or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
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 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.
The transitory loss of hearing calls for the immediate cessation of medication.
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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
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 anticoagulants may occur. Concurrent administration of acetazolamide and aspirin may result in severe acidosis and increase central nervous system toxicity. Dose adjustment 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.
Because of possible additive effects, concomitant use with other carbonic anhydrase inhibitors is not advisable.
By increasing the pH of renal tubular urine, acetazolamide reduces the urinary excretion of amphetamine and quinidine and so may enhance the magnitude and the duration of effect of amphetamines and enhance the effect of quinidine.
Ciclosporin: Acetazolamide may elevate ciclosporin levels.
Methenamine: Acetazolamide may prevent the urinary antiseptic effect of methenamine.
Lithium: Acetazolamide increases lithium excretion and the blood lithium levels may be decreased.
Sodium bicarbonate: Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation.
4.6 Fertility, pregnancy and lactation
Use in pregnancy: 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 acetazolamide should not be used in pregnancy, especially during the first trimester.
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.
4.7 Effects on ability to drive and use machines
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.
4.8 Undesirable effects
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.
Gastro-intestinal disturbances including nausea, vomiting and diarrhoea. 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, taste disturbance, some loss of appetite, flushing, headache, dizziness, fatigue, irritability, depression, thirst, and polyuria, reduced libido, and occasional instances of drowsiness and confusion. Rarely, photosensitivity has been reported.
Other occasional adverse reactions include: hearing disturbances and tinnitus, urticaria, malaena, glycosuria, haematuria, abnormal liver function, renal failure and rarely, hepatitis or cholestatic jaundice, flaccid paralysis and convulsions.
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 withdrawal of the medication.
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
4.9 Overdose
No specific antidote. Supportive measures with correction of electrolyte and fluid balance. Force fluids.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Carbonic anhydrase inhibitors.
ATC Code: S01EC01
Acetazolamide is an inhibitor of carbonic anhydrase. By inhibiting the reaction catalysed by this enzyme in the renal tubules, acetazolamide increases the excretion of bicarbonate and of cations, chiefly sodium and potassium, and so promotes alkaline diuresis.
Continuous administration of acetazolamide is associated with metabolic acidosis and resultant loss of diuretic activity. Therefore, the effectiveness of Acetazolamide tablets in diuresis diminishes with continuous use.
By inhibiting carbonic anhydrase in the eye, acetazolamide decreases intraocular pressure and is therefore useful in the treatment of glaucoma.
5.2 Pharmacokinetic properties
Acetazolamide is fairly rapidly absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 2 hours after administration by mouth. It has been estimated to have a plasma half-life of about 4 hours. It is tightly bound to carbonic anhydrase and accumulates in tissues containing this enzyme, particularly red blood cells and the renal cortex. It is also bound to plasma proteins. It is excreted unchanged in the urine; renal clearance being enhanced in alkaline urine.
5.3 Preclinical safety data
Not applicable.
6.1 List of excipients
Lactose Maize starch
Pregelatinised maize starch
Povidone
Sucrose
Sodium starch glycollate Magnesium stearate
6.2 Incompatibilities
None stated.
6.3 Shelf life
36 months all pack sizes.
6.4 Special precautions for storage
Store below 25°C in a dry place.
Keep container tightly closed, protect from light.
6.5 Nature and contents of container
High-density polyethylene containers with polythene closures fitted with dessicant capsule insert within lid and sealed with a thick paper membrane. OR
High density polyethylene containers with polythene lids and polyurethane/polythene inserts or polypropylene containers with polypropylene or polythene lids and polyurethane/polythene inserts.
Pack sizes: 100, 112 and 500 tablets
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited 11 Boumpoulinas Street,
3rd floor, 1060 Nicosia Cyprus
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0001
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/11/2008
10 DATE OF REVISION OF THE TEXT
22/08/2016