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EYTAZOX 250 MG PROLONGED-RELEASE CAPSULES

Active substance(s): ACETAZOLAMIDE / ACETAZOLAMIDE / ACETAZOLAMIDE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Eytazox 250 mg Prolonged-Release Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 250 mg acetazolamide.
Also contains sunset yellow FCF.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Prolonged-release capsule, hard.
Hard gelatin capsule with a clear body and orange cap, printed with ‘AM250’ in
black ink’, containing round orange pellets.

4
4.1

CLINICAL PARTICULARS
Therapeutic indications
Glaucoma

4.2

Posology and method of administration
Capsules should be swallowed whole. Do not chew or crush.
Adults:

One or two 250mg capsules a day.

Children:

This product is not intended for administration to children.

Use in Elderly Patients: Eytazox should 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.
Use in Patients with Renal Impairment: In patients with moderate to severe renal
impairment, the dose should not exceed 250mg per day or the dosage interval should
be increased to every 12 hours.

4.3

Contraindications
Eytazox is contra-indicated in situations in which sodium and/or potassium blood
levels are depressed, in cases of marked renal impairment and liver disease or
dysfunction, suprarenal gland failure, and hyperchloraemic acidosis. Eytazox should
not be used in patients with liver disease or impairment of liver function including
cirrhosis as this may increase the risk of hepatic encephalopathy. Eytazox is contraindicated in patients with hypokalemia and hyponatraemia.
Long-term administration of Eytazox is contra-indicated in patients with chronic noncongestive 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.
Eytazox should not be used in patients hypersensitive to sulfonamides or other
sulfonamide derivatives including acetazolamide or any excipients in the formulation.

4.4

Special warnings and precautions for use
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 antiepileptic agents in several indications. A meta-analysis of randomized placebocontrolled 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 Eytazox Pronlonged-Release Capsules 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 sulfonamides 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
Eytazox therapy.
Hypersensitivity reactions may recur if a sulfonamide or sulfonamide derivative is readministered, 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 increases 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.
Acetazolomide Prolonged-Release Capsules contains sunset yellow FCF (E110)
which may cause allergic reactions.

4.5

Interaction with other medicinal products and other forms of interaction
Eytazox is a sulfonamide derivative. Sulfonamides 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 Eytazox is given with cardiac
glycosides or hypertensive agents.
When given concomitantly, Eytazox Prolonged-Release Capsules 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.

4.6

Fertility, pregnancy and lactation
Use in pregnancy: Acetazolamide has been reported to be teratogenic (defects of the
limbs) 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, Eytazox Prolonged-Release Capsules 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
Eytazox Prolonged-Release Capsules is administered to lactating women.

4.7

Effects on 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.

4.8

Undesirable effects
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; some loss of appetite; taste disturbance, polyuria, flushing, thirst,
headache, dizziness, fatigue, irritability, excitement, ataxia, depression, reduced
libido and occasional instances of drowsiness and confusion. Rarely, photosensitivity
has been reported.
During long-term therapy, metabolic acidosis and electrolyte imbalance, including
hypokalaemia and hyponatraemia may occasionally occur. Hypokalaemia is
generally transient and is rarely clinically significant. Osteomalacia with long-term
phenytoin therapy, hyperglycaemia and hypoglycaemia may occasionally occur
during long-term therapy. The acidosis can usually be corrected by the
administration of bicarbonate.
Transient myopia has been reported. This condition invariably subsides upon
diminution or discontinuation of the medication.
Gastro-intestinal disturbances such as nausea, vomiting and diarrhoea.
Eytazox is a sulfide derivative and therefore some side-effects similar to those caused
by sulfonamides have occasionally been reported. These include fever,
agranulocytosis, thrombocytopenia, thrombocytic purpura, leukopaenia, 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.
Other occasional adverse reactions include: urticaria, melaena, haematuria,
glycosuria, impaired hearing and tinnitus, abnormal liver function, renal failure and
rarely; hepatitis or cholestatic jaundice, flaccid paralysis, and convulsions.

Long-term therapy with acetazolamide increases the risk of nephrolithiasis.
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 (Website: www.mhra.gov.uk/yellowcard).

4.9

Overdose
No specific antidote.
Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state and central nervous effects
might be expected to occur. Serum electrolyte levels, (particularly potassium) and
blood pH should be monitored.
Supportive measures are required to restore electrolyte and pH balance. The acidotic
state can usually be corrected by the administration of bicarbonate.
Despite its high intra-erythrocytic distribution and plasma protein binding properties,
acetazolamide is dialyzable. This may be particularly important in the management
of acetazolamide overdosage when complicated by the presence of renal failure.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Carbonic Anhydrase Inhibitors, ATC code S01E C01.
Acetazolamide is a potent inhibitor of the enzyme carbonic anhydrase; the enzyme
that catalyses the reversible reaction involving the hydration of carbon dioxide and
the dehydration of carbonic acid. In the eye, this inhibitory action of acetazolamide
decreases the secretion of the aqueous humor and results in a drop of intraocular
pressure and is thus used to treat glaucoma.

5.2

Pharmacokinetic properties
Eytazox 250 mg Prolonged-Release Capsules is a sustained release formulation
designed to obtain a smooth and continuous clinical response. Acetazolamide is
readily absorbed after oral administration and binds tightly to plasma proteins as well
as to the enzyme carbonic anhydrase. The drug begins to accumulate in tissues in
which this enzyme is present notably red blood cells and the renal cortex. It is also
bound to plasma proteins.
Peak plasma levels of the drug are reached 1-3 hours after oral administration with
whole blood levels reaching peak concentrations approximately one hour later.
Plasma levels decay more rapidly than red blood cell or whole blood levels with the
elimination frequently being biphasic. The first phase having a half-life in 2 hours
and the second phase in 13 hours. This terminal phase half-life corresponds to the
leakage from red blood cells.
Acetazolamide is completely cleared by the renal route with the measured unbound
renal clearance being some 5-6 times greater than creatinine clearance. Overall,
clearance is dependent also on plasma protein binding.

5.3

Preclinical safety data
Nothing of note to the prescriber.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Coated Pellets:
Hypromellose
Microcrystalline cellulose
Purified talc
Colloidal anhydrous silica
Ethylcellulose
Light liquid paraffin
Opaspray orange [hydroxypropylcellulose, titanium dioxide (E171), talc & sunset
yellow FCF (E110)]
Capsule Shell:
Gelatin
Titanium dioxide (E171)

Iron oxide yellow (E172)
Iron oxide red (E172)

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
36 months

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container
PVC/PVdC foiled aluminium blister.
Pack of 30 capsules.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Auden Mckenzie (Pharma Division) Ltd
Whiddon Valley
Barnstaple
North Devon
EX32 8NS
United Kingdom.

8

MARKETING AUTHORISATION NUMBER(S)
PL 17507/0139

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

19/06/2013

10

DATE OF REVISION OF THE TEXT
14/06/2016

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Source: Medicines and Healthcare Products Regulatory Agency

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