INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo DIAMOX* Tablets 250 mg
DIAMOX* Sodium Parenteral 500 mg/Vial

SCHEDULING STATUS
Zimbabwe pp
Schedule 3

PROPRIETARY NAME
(and dosage form)

DIAMOX* Tablets 250 mg
DIAMOX* Sodium Parenteral 500 mg/Vial

COMPOSITION
Tablets: Each tablet contains 250 mg of
acetazolamide.
Parenteral: Each vial contains acetazolamide sodium equivalent to 500 mg acetazolamide and is supplied as a sterile powder requiring reconstitution. The bulk solution is adjusted to pH 9.2 prior to lyophyllisation.

PHARMACOLOGICAL CLASSIFICATION
A. 18.1 Diurectics.

PHARMACOLOGICAL ACTION
DIAMOX*, a carbonic anhydrase inhibitor, is a non-bacteriostatic sulphonamide derivative which inhibits the enzyme carbonic anhydrase wich decreases formation of hydrogen and bicarbonate ions from carbon dioxide and water and reduces the availability of these ions for active transport. The agents reduce plasma bicarbonate concentration and increase plasma chloride concentration, producing systemic metabolic acidosis.
Acetazolamide acts as an antiglaucoma agent by lowering intraocular pressure by decreasing the production of aqueous humour by 50 to 60%.
Acetazolamide acts as an anticonvulsant by an uncertain mechanism. The inhibition of carbonic anhydrase in the central nervous system (CNS) may increase carbon dioxide tension, resulting in a retardation of neuronal conduction.
Acetazolamide acts against altitude sickness, possibly by producing metabolic acidosis resulting in increased respiratory drive and arterial oxygen tension and/or by diuresis.

PHARMACOKINETICS:
Acetazolamide is extensively (90%) protein bound. The tablets are well absorbed, have a half-life of 10-15 hours, time to peak effect of 2-4 hours, and 90% to 100% of the dose is excreted unchanged in the urine within 24 hours.
DIAMOX* I.V. has peak effect within 15 minutes and a duration of action of 4-5 hours.

INDICATIONS
DIAMOX* is indicated for the treatment of open-angle glaucoma, treatment of secondary glaucoma and treatment of angle-closure glaucoma.
DIAMOX* is indicated as an adjunct to other anti-convulsants in the management of absence seizures (petit mal); generalized tonic-clonic seizures (grand mal); mixed seizure patterns; simple partial seizure patterns and myoclonic seizure patterns. Tolerance to the anticonvulsant effect of acetazolamide develops rapidly, over weeks or months in some patients.
DIAMOX* Tablets are used to decrease the incidence and/or severity of symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness and fatgue) associated with acute altitude sickness in mountain climbers who are attempting rapid ascent and in those who are very susceptible to altitude sickness despite gradual ascent.
DIAMOX* Tablets will have little or no effect on established symptoms.
The use of acetazolamide for rapid ascent does not obviate the need for prompt descent if sever forms of high altitude sickness, such as high altitude pulmonary edema (HAPE) or high altitude cerebral adema, occur.

CONTRA-INDICATIONS:
DIAMOX* therapy is contra-indicated in situations in situations in which sodium and/or potassium serum levels are depressed; in cases of marked kidney or liver disease or dysfunction; in adrenal gland failure or adreno-cortical insufficiency e.g., Addison’s disease and in hyperchloremic acidosis.
In patients with cirrhosis, use may precipitate the development of hepatic encephalopathy. In patients with a history of calcium containing renal calculi this condition may be exacerbated or induced.
Sensitivity to Carbonic Anhydrase Inhibitors.
Long-term administration of DIAMOX* is contra-indicated in patients with angle-closure glaucoma, since organic closure of the angle may occur in spite of lowered intraocular pressure.

Use during pregnancy and lactation:
The safety of DIAMOX* during pregnancy and lactation has not been established. With high doses teratogenic and embryocidal effects have been demonstrated in rodents.

DOSAGE AND DIRECTIONS FOR USE
Tablets:
Usual adult dose:
Antiglaucoma agent
Initial –Oral. 250 mg one to four times a day
Maintenance –to be titrated according to patient response; lower doses may be sufficient.
Secondary glaucoma and preoperative lowering of intraocular pressure Oral –250 mg every four hours. Some patients may respond to 250 mg two times a day. In some acute cases, am initial dose of 500 mg followed by 125 or 250 mg every four hours may be preferable.
Anticonvulsant:
Oral –4 –30 mg (usually 10 mg initially) per kg of body mass a day in up to 4 divided doses; usually 375 mg to 1 g a day.
When acetazolamide is added to existing anticonvulsant therapy, an initial dose of 4 to 5 mg per kg of body mass per day in addition to existing medications is recommended. Dosage may be increased as necessary. Changes from other anticonvulsants to acetazolamide or withdrawal of acetazolamide therapy should be gradual to prevent increased seizures activity and possible status epilepticus.
Altitude Sickness –acute agent:
Oral –250 mg two to four times a day.
Note:
During rapid ascent, such as in rescue or military operations, 1 000 mg a day is recommended. Therapy should preferably be initiated 24 to 48 hours before ascent and, while at high altitude, continued for 48 hours or longer as necessary to control symptoms.
Note:
For use as an anticonvulsant or in open-angle glaucoma, dosage greater than 1 g per day usually does not produce and increased effect.

Usual Paediatric Dose:
Glaucoma:
Oral –8 to 30 mg per kg of body mass, usually 10 to 15 mg per kg or 300 to 900 mg per square meter of body surface area a day in divided doses.
Anticonvulsant:
See Usual Adult Dose above.

I.V. INJECTION:
Preparation of Parenteral solution: Each vial containing 500 mg of DIAMOX* acetazolamide sodium parenteral should be reconstituted with at least 5 mL sterile distilled water prior to use.
Reconstituted solutions retain their physical and chemical properties for 3 days under refrigeration at 2 to 8ºC, or 12 hours at room temperature 15 to 30ºC.
CONTAINS NO PRESERVATIVE. The direct intravenous route of administration is preferred. Intramuscular administration is not recommended.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit.
Usual Adult Dose:
Antiglaucoma agent:
For rapid initial lowering of intraocular pressure: intravenous, the equivalent of acetazolamide –500 mg. Alternatively, 250 mg intravenously plus 250 mg intramuscularly may be given.
Note:
Parenteral administration may be repeated in two to four hours in some acute cases but therapy is usually continued with oral acetazolamide, depending on the patient’s response.
Note:
For other uses or even the patient is unable to take oral medication, acetazolamide may be given parenterally in dosages equivalent to those recommended for the oral tablets.
Usual Paediatric Dose:
Antiglaucoma Agent:
Acute glaucoma: Intravenous or the equivalent of acetazolamide –5 to 10 mg per kg of body mass every six hours.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Serious side-effects which have been reported more frequently with acetazolamide include unuasual tiredness or weakness which may indicate acidosis, blood dyscrasias and hypocalcaemia. Crystalluria, renal calculus, renal colic or sulphonamide-like nephrotoxicity and mental depression have been reported less frequently.
Serious side-effects which have rarely been reported, include acidosis, blood dyscrasias such as aplastic anaemia, agranulocytosis, leucopenia, thrombocytopenia and thrombocytopenic purpura; bloody or black, tarry stools, cholestatic jaundice, clumsiness, confusion, convulsions, hypersensitivity reactions, hypokalaemia, near sightedness, ringing or buzzing in the ears and severe muscle weakness or trembling.
Other side-effects include diarrhoea; drowsiness; general malaise; allergic skin reactions, excitement, fever, thirst, dizziness, ataxia, headache; increase in frequency or volume of urination; increased sensitivity of eyes to sunlight; loss of appetite; loss of taste and smell; metallic taste in the mouth; nausea or vomiting; numbness, tingling or burning in the hands, fingers, feet, toes, mouth, tongue, lips or anus; weight loss.
DIAMOX* should be used with care in elderly patients and where the following medical problems exist: diabetes mellitus; gout; respiratory acidosis or impaired alveolar function due to pulmonary disease; oedema or obstruction.
Intramuscular injections are painful owing to the alkalinity of the solution.

INTERACTIONS
When amphetamines; anticholinergics, especially atropine and related compounds; mecamylamine or quinidine are used concurrently with DIAMOX*, their therapeutic and/or side effects may be enhanced or prolonged as a result of decreased excretion caused by alkalinization of urine.
The efficacy of methamine is reduced by DIAMOX* and concurrent use is not recommended.
Concurrent use with glucocorticoid or mineralo-corticoid adrenocorticoids, corticotrophin or parenteral amphotericin B may result in severe hypokaleamia and/or hypernatremia or oedema as well as an increased in the risk of hypocacemia and osteoporosis.
Concurrent use of adrenocorticoids or corticotrophin with acetazolamide sodium may increase the risk of hypernatraemia and/or oedema because these fluids cause sodium and fluid retention.
The hypoglycaemic response to insulin or oral antidiabetic agents may be decreased and dosage adjustments may be required.
Osteopenia induced by barbiturates, carbamazepine, phenytoin or primidone may be enhanced by DIAMOX*.
The solubility of ciprofloxacin in the urine may be reduced and the patient should be monitored for signs of crystalluria and nephrotoxicity.
Concurrent use with digitalis glycosides may enhance the possibility of digitalis toxicity associated with hypokalaemia.
DIAMOX* may enhance concurrent diuretic therapy, increased the half-life of ephedrine, retard renal excretion of mexiletine, enhanced blockage of neuromuscular blocking agents and increase the risk of salicylate intoxication.
DIAMOX* may increase lithium excretion. Concurrent use with mannitol or urea may lead to increased reduction of intraocular pressure as well as increased diuresis.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Symptoms of overdosage are listed under “Side-effects”. Clinical signs include hypokalaemia, diuresis, metabolic acidosis and acidotic coma.
Treatment is supportive.

IDENTIFICATION
Tablets: Round, convex white tablets, engraved “Lederle” on the side and scored in quarters on the other.
Parenteral: Clear glass vials containing a sterile white powder.

PRESENTATION
Tablets: Blister pack of 30 and 100 tablets each.
Vials: Each vial contains 500 mg acetazolamide in the form of the sodium salt.

STORAGE INSTRUCTIONS
Store at room temperature below 25ºC.
Keep out of reach of children.
Reconstituted solutions retain their physical and chemical properties for 3 days under refrigeration at 2 to 8ºC, or 12 hours at room temperature 15 to 30ºC.

REFERENCE NUMBERS
Tablets: H1786 (Act 101/1965)
Parenteral: H1929 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF APPLICANT
PHARMAFRICA (PTY) LTD
33 Hulbert Road
New Centre
Johannesburg
2001

DATE OF PUBLICATION OF THIS PACKAGE INSERT
September 1995

Updated on this site: May 2014
Source: Pharmaceutical Industry


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