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ACETAZOLAMIDE TABLETS BP 250MG

Active substance(s): ACETAZOLAMIDE / ACETAZOLAMIDE / ACETAZOLAMIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Acetazolamide Tablets 250 mg.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 250 mg of Acetazolamide.
For excipients, see 6.1

3

PHARMACEUTICAL FORM
Acetazolamide Tablets are presented as white flat bevelled edge tablets
engraved with R and crescent moon logo on one side and A / 303 either side of
a break-line on the other.
The tablet can be divided into equal doses.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications
Acetazolamide Tablets 250 mg are indicated in the treatment of
1. 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. Acetazolamide acts on inflow,
decreasing the amount of aqueous secretion.
2. Abnormal retention of fluids
Acetazolamide acts on the reversible hydration of carbon dioxide and
hydration of the carbonic acid reaction in the kidney resulting in renal loss of
bicarbonate ion which carries out sodium, water and potassium.
It can be used in conjunction with other diuretics when effects on several
segments of the nephron are desirable in the treatment of fluid retaining states.

3. Epilepsy
When used in conjunction with other anticonvulsants best results have been
seen in petit mal in children. Good results have been seen in both children and
adults with grand mal, mixed seizure patterns and myoclonic jerk patterns.

4.2

Posology and method of administration
Route of administration Oral
Dosage
1. Glaucoma (simple acute congestive and secondary)
Adults: 1-4 tablets, daily, in divided doses for amounts over 250 mg daily.
2. Abnormal retention of fluid:

congestive heart failure
drug - induced oedema

Adults: initially 1 - 1½ tablets once daily in the morning
If after an initial response, 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 obtained on a regime of 1 - 1½ tablets daily for two days, rest
a day and repeat, or merely on alternate days.
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.
In cases of fluid retention associated with pre-menstrual tension, a daily dose
of 125 - 375mg is suggested.
3. Epilepsy
Adults: 250 - 1000 mg daily in divided doses
Children: 8 - 30 mg / kg body-weight daily in divided doses, and not to exceed
750 mg daily.
The change from other preparations to acetazolamide should be gradual.
Elderly:
Caution should be exercised in using acetazolamide in elderly patients or those
with potential obstruction in the urinary tract or with disorders disrupting their
electrolyte balance or with liver dysfunction.

4.3

Contraindications
Known hypersensitivity to acetazolamide, sulphonamides or any of the
ingredients.
Depressed sodium and/or potassium blood serum levels.
Marked kidney and liver disease or dysfunction.
Suprarenal gland failure, and hyper chloremic acidosis.
Should not be used in patients with hepatic cirrhosis as this may increase the
risk of hepatic encephalopathy.
Long term therapy is contraindicated in patients with chronic congestive
angle-glaucoma since it may permit organic closure of the angle to occur
while the worsening glaucoma is masked by lowered intra-ocular pressure.

4.4

Special warnings and precautions for use
Suicidal ideation and behaviour have been reported in paients 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 it 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 monitoring of 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 diminution or
cessation of acetazolamide therapy.

In patients with pulmonary obstruction or emphysema where alveolar
ventilation may be impaired, acetazolamide which may aggravate acidosis,
should be used with caution.
Patients with a past history of renal calculi should be warned that
acetazolamide may cause further renal calculi.
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactose deficiency or glucose-galactose malabsorption should not take this
medicine.

4.5

Interaction with other medicinal products and other forms of interaction
When given concurrently, 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.
Concurrent administration with high dose aspirin may potentiate the adverse
reactions of acetazolamide. Adjustment of dose may be required when
acetazolamide is given with cardiac glycosides or hypertensive agents. It can
potentiate the effects of folic acid antagonists, hypoglycaemics and oral
anticoagulants.
Ciclosporin; Acetazolamide may elevate ciclosporin levels.
Methanamine: Acetazolamide may prevent the urinary antiseptic effect of
methanamine.
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 calculi.

4.6

Pregnancy and lactation

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.
Acetazolamide has been detected in low levels in the milk of lactating women
who have taken this drug. 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 necrosis. 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
The reported side effects include paraesthesia, particularly a tingling feeling in
the extremities, some loss of appetite, altered taste sensation, polyuria,
polydipsia, flushing, thirst, headache, dizziness, fatigue, irritability,
depression, reduced libido and occasional instances of drowsiness and
confusion. Rarely photosensitivity has been reported.
Transient myopia has been reported which invariably subsides upon reduction
or withdrawal of the drug.
During long term therapy, metabolic acidosis and electrolyte imbalance may
occasionally occur. This can usually be corrected by the administration of
bicarbonate.
Gastro-intestinal disturbances such as nausea, vomiting and diarrhoea.
Acetazolamide being a sulphonamide derivative may occasionally cause 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 have been reported. Rarely, fulminant hepatic necrosis has been
reported.

Other adverse reactions reported occasionally include urticaria, melena,
haematuria, glycosuria, impaired hearing and tinnitus, abnormal liver function,
renal failure and rarely, hepatitis or cholestatic jaundice, flaccid paralysis and
convulsions.
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
There is no specific antidote. Supportive measures with correction of
electrolyte and fluid balance are helpful. Symptomatic treatment should be
carried out.

5

PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: Carbonic anhydrase inhibitors, acetazolamide
ATC code: S01E C01

5.1

Pharmacodynamic properties
Acetazolamide is a potent, reversible inhibitor of carbonic anhydrase. The
enzyme catalyses the hydration of carbon dioxide and dehydration of carbonic
acid.
Action on the kidney: Following the administration of acetazolamide, the urine
volume promptly increases. The normally acidic pH becomes alkaline. The
urinary concentration of the bicarbonate anion increases and is matched by
sodium and substantial amounts of potassium.
The urinary concentration of chloride falls. The increased alkalinity of the
urine is necessarily accompanied by a decrease in the excretion of titratable
acid and of ammonia.
The above sequence of events may be attributed to the inhibition of H+
secretion by the renal tubule. This inhibition is indirect in the proximal tubule,
is the consequence of inhibition of cytoplasmic carbonic anhydrase, which
decreases the availability of protons Na + - H + exchange. In addition, carbonic

anhydrase bound to the brush-border membrane is also inhibited. This slows
the dehydration of carbonic acid in the lumen and, thereby, the diffusion of
CO2 into the tubular cell. The overall effect is that bicarbonate reabsorption in
proximal tubule is reduced by some 80%. More than half of this rejected
bicarbonate is reabsorbed in later segments of the nephron by mechanisms that
do not involve carbonic anhydrase and that are not yet fully characterised.
Acetazolamide also inhibits H+ secretion by some segments of the distal
nephron. These distal mechanisms, which have a lower capacity than do those
in the proximal tubule, apparently depend on the cytoplasmic form of carbonic
anhydrase but not on the membrane-bound form of the enzyme.
Effect on plasma composition: Acetazolamide increases the urinary excretion
of bicarbonate and fixed cation, mostly sodium. As a result, the concentration
of bicarbonate in the extracellular fluid decreases and metabolic acidosis
results. In metabolic acidosis, the renal response to acetazolamide is greatly
reduced; conversely, it is enhanced with metabolic alkalosis. Factors other
than the amount of filtered bicarbonate must be determinants of drug action
since the extracellular alkalosis of potassium depletion (with presumed
intracellular acidosis) decreases the diuretic response.
Acetazolamide produces a marked increase in potassium excretion,
attributable to enhanced secretion in the distal nephron. The effects on
potassium are most prominent in acute experiments.
Eye: The presence of carbonic anhydrase in a number of intraocular structures,
including the ciliary processes, and the high concentration of bicarbonate in
the aqueous humour have focussed attention on the role that the enzyme might
play in the secretion of aqueous humor. Acetazolamide reduces the rate of
aqueous humor formation; intraocular pressure in patients with glaucoma is
correspondingly reduced. This action of the drug appears to be independent of
systemic acid-base balance.
Central nervous system: An action of acetazolamide on the CNS was first
suggested by the frequency of paraesthesias and somnolence as side effects.
Subsequently, the drug was found to inhibit epileptic seizures and to decrease
the rate of formation of spinal fluid. Metabolic acidosis from ketogenic diets
diminishes epileptic seizures, and acetazolamide by virtue of its action on the
kidney leads to the production of a systemic acidosis. However, there is
undoubtedly a more direct action on CNS function. And increase in local CO2
tension may result from inhibition of the enzyme in the brain, the choroid
plexus, or the erythrocytes of the cerebral blood. The exact role of carbonic
anhydrase in brain function remains unknown. The concentration of the
enzyme varies from one site to another within the brain. Acetazolamide may
reduce the rate of cerebrospinal fluid formation by the choroid plexus, but it
may also transiently elevate cerebrospinal fluid pressure as a result of an
increase in intracranial blood flow.
5.2

Pharmacokinetic properties

Acetazolamide is readily absorbed from the gastrointestinal tract. Peak
concentration in plasma occur within about 2 hours and effective plasma
concentration persists for up to 12 hours. It is reported to be extensively bound
to plasma proteins. Acetazolamide is tightly bound to plasma proteins.
Acetazolamide is tightly bound to carbonic anhydrase and hence, present in
greater amounts in those tissues in which the enzyme is present in high
concentration, particularly the erythrocytes and the renal cortex. Some
carbonic anhydrase inhibitors do not penetrate the erythrocyte. It is not
metabolised.
It is excreted by the kidney both by active tubular secretion and passive
reabsorption are involved. Excretion is complete within 24 hours.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber that are additional
to that already included in other sections of the SPC.

PHARMACEUTICAL PARTICULARS
6.1

List of excipients

Dicalcium phosphate
Maize starch
Pregelatinised maize starch
Magnesium Stearate
Sodium starch glycolate Type A

6.2

Incompatibilities
None reported.

6.3

Shelf life

Opaque plastic containers: 36 months.
Blister packing: 24 months.

6.4

Special precautions for storage
Keep out of the reach and sight of children.
Store in container provided and protect from heat, light and moisture.

6.5

Nature and contents of container
1. Opaque plastic containers composed of polypropylene tubes and
polyethylene tamper evident closures for pack sizes of 28, 30, 42, 50, 56,
60, 84, 90, 100 and 112.
3. Blister packs of aluminium/opaque PVC, it is subsequently packed in
printed boxboard cartons in pack sizes of 28, 30, 42, 56, 60, 84, 90 and 112.

6.6

Instructions for use/handling
No special instructions for use/handling.

7

MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
Units 3 & 4, Quidhampton Business Units
Polhampton Lane
Overton
Hampshire
RG25 3ED
United Kingdom

8.

MARKETING AUTHORISATION NUMBER
PL 20416/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
12 January 2004

10

DATE OF REVISION OF THE TEXT
06/02/2017

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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