ATC Code: S01EC Carbonic anhydrase inhibitor
Carbonic anhydrase inhibitor No. 6063
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Main brand names/main trade names
Acetamox; Ak-Zol; Apo-Acetazolamide; Atenezol; AZM-Tab;
Cidamex; Daranide; Dazamide; Defiltran; Dehydratin; Diacarb;
Diamox; 4-Diamox; Didoc; Diluran; Diuramid; Diureticum-
Holzinger; Diuriwas; Diutazol; Donmox; Duiramid; Edemox;
Eumicton; Fonurit; Glaupax; Glupax; MZM; Natrionex; Nephramid;
Nephramide; Neptazane; Phonurit; Storzolamide; Vetamox.
1.6 Main manufacturers/main importers
125 mg, 250 mg tablets
500 mg sustained release capsules
Intravenous injection 500 mg/5 cc
2.1 Main risks and target organs
Overdoses of diuretics are rare and problems most
frequently involve chronic overmedication or poor monitoring of
effects or drug-drug interactions that are not anticipated by
the clinician. Main toxic effects are on the kidneys with
diuresis of water, sodium, potassium, and most importantly
bicarbonate with resultant dehydration. More caution is
warranted with patients at higher risk for renal abnormal
function including patients with any renal disease, diabetes
mellitus, exposure to nephrotoxic contrast agents and
borderline fluid and/or electrolyte status.
2.2 Summary of clinical effects
Patients with either acute or chronic overdosage with
acetazolamide may show signs of dehydration with thirst,
lethargy, confusion, poor skin turgor, and prolonged capillary
refill time, but may have a paradoxical continued diuresis.
Electrolyte abnormalities include hyponatremia, hypokalemia,
and a non-anion gap hyperchloremic metabolic acidosis in the
more than mild ingestion which may lead to further
deterioration in mental status, production of seizures,
electrocardiographic abnormalities, and arrhythmias. Prior
renal insufficiency will lead to increased toxicity at a given
dose. There are idiosyncratic reactions producing bone marrow
suppression with hepatic and renal insufficiency.
Acetazolamide may also precipitate in the renal tubules
producing calculi with renal colic. Hypokalemia may lead to
muscular weakness, hyporeflexia, and hypochloremic metabolic
In chronic therapy, especially in geriatric patients, a chronic
metabolic acidosis may lead to a chronic compensatory
hyperventilation which increases pulmonary vascular resistance
and decreases left ventricular function. This can be
especially significant in patients on concurrent beta-blocker
or calcium channel blocker therapy. The ventricular
fibrillation threshold may then be reduced.
Cardiac arrhythmias may occur due to potassium deficiency.
Abuse or overdose may result in pancreatitis. Hyperglycemia,
hyperuricemia, and hyperlipidemia may occur with acute overdose
or in chronic use or abuse. Hypersensitivity reactions such as
rash, photosensitivity, thrombocytopenia, and pancreatitis are
Diagnosis should be considered in a patient that
demonstrates an apparently paradoxical alkaline urine in the
face of a metabolic acidosis or patients with unexplained
dehydration or hypokalemia (Spratt et al., 1982).
Acetazolamide levels are available at some centers but are
rarely useful in the acute setting. Measurement of
electrolytes, urine pH, and blood gas analysis will help to
support the diagnosis. Patients that may have access to
acetazolamide include climbers, and patients with glaucoma or
2.4 First aid measures and management principles
Since the complications of an overdose of strictly
acetazolamide are relatively rare, invasive or noxious
interventions such as syrup of ipecac or gastric lavage are
probably not warranted in most cases. Gastrointestinal
decontamination with activated charcoal is probably warranted
if the patient presents within 1-2 hours post-ingestion,
especially in the face of serious underlying disease.
Intervention should be targeted at replacing any fluid and
electrolyte abnormalities initially with intravenous isotonic
crystalloid solutions. Obtaining serum electrolytes including
serum bicarbonate and urinalysis with urine pH is warranted
except in the most trivial ingestion. Venous or arterial blood
gas measurement may be helpful in the severely or chronically
overdosed patient to better define the patient's acid-base
status. Sodium bicarbonate infusion may be necessary if serum
pH is below 7.10 and does not respond to initial volume
resuscitation (Goldfrank et al, 1994). A too rapid correction
may exacerbate electrolyte abnormalities. For hypotension,
vigorous fluid hydration is necessary before using
vasopressors, and invasive monitoring with at least a central
venous pressure monitor is recommended.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Acetazolamide is of synthetic origin.
3.2 Chemical structure
Molecular weight: 222.2
Molecular formula: C4H6N4O3S2
3.3 Physical properties
3.3.1 Properties of the substance
Acetazolamide exists as a white to faintly
yellowish-white, odourless crystalline powder.
Acetazolamide is very slightly soluble in water and only
slightly soluble in ethanol (~750 g/l); it is
practically insoluble in ether and chloroform. The pH
of a suspension 1g Acetazolamide in 50 ml water is 4.0
to 6.0 (McEvoy, 1995).
Acetazolamide has a melting point of about 260 °C, with
decomposition (Moffat, 1986).
The pKa values are 7.2 and 9.0 (Dollery, 1991).
3.3.2 Properties of the locally available formulation
3.4 Other characteristics
3.4.1 Shelf-life of the substance
Solutions of acetazolamide are stable for one
week after reconstitution, but it is recommended to use
the solution within 24 hours (McEvoy, 1995).
3.4.2 Shelf-life of the locally available formulation
To be completed by each center.
3.4.3 Storage conditions
Acetazolamide tablets and extended-release
capsules should be stored in a well-closed container at
15 to 30°C.
No data found.
3.4.5 Specific properties and composition
No data found.
1. Preoperative management of closed-angle glaucoma, or as
an adjunct in the treatment of open-angle glaucoma.
2. Abnormal retention of fluid: drug-induced oedema, obesity,
and congestive cardiac failure.
4. Prevention or amelioration of acute high-altitude (mountain)
sickness when rapid ascent is necessary or in subjects who are
particularly susceptible to altitude sickness despite gradual
ascent. However, this is not an approved indication for the
use of acetazolamide.
5. Metabolic alkalaemia.
6. Periodic paralysis
(Dollery, 1991; McEvoy, 1995; Reynolds, 1993).
4.2 Therapeutic dosage
In the treatment of glaucoma the usual dose is 250 to
1000 mg by mouth daily, in divided doses for amounts
over 250 mg daily, or as a controlled release
When the patient with glaucoma is unable to take oral
medicine, 500 mg of acetazolamide may be administered IV
or IM in adults (McEvoy, 1995).
Abnormal retention of fluid
For congestive heart failure, toxaemia and oedema the
dose is 250-375 mg once daily in the morning. Response
may decrease with time and it may be helpful to omit the
drug every third day, or to use alternate day
For obesity the dose is 250-375 mg daily, which may be
used on alternate weeks. (Dollery, 1991)
Acetazolamide used in the treatment of epilepsy is
administered in doses of 250 to 1000 mg daily in divided
doses for amounts over 250 mg daily (Reynolds,
For the treatment of mountain sickness the usual dose is
500 to 1000 mg daily.
In patients with metabolic alkalaemia acetazolamide 2.5
to 5 mg per kg body-weight is administered intravenously
(Berthelsen et al. as quoted in Reynolds, 1993)
Glaucoma and epilepsy
A suggested dose for children for glaucoma or epilepsy
is 8 to 30 mg per kg daily (Reynolds, 1993). In acute
glaucoma in children, 5 to 10 mg/kg may be administered
IM or IV every 6 hours (McEvoy, 1995).
Abnormal retention of fluid
As a diuretic in children, an acetazolamide dosage of
5 mg/kg or 150 mg/m2 may be administered orally or IV
once daily in the morning (McEvoy, 1995).
1. Renal hyperchloraemic acidosis.
2. Addison's disease and all types of suprarenal gland
3. Conditions where there is known depletion of sodium and
potassium (at least until this is treated).
4. Long-term administration is contraindicated in patients with
chronic closed angle-closure glaucoma.
5. Known sensitivity to sulfonamides.
6. Acetazolamide should not be used to alkalinize urine
following salicylate overdose since it may worsen metabolic
acidosis (Ellenhorn, 1988).
5. ROUTES OF ENTRY
Acetazolamide is administered orally as tablets or
controlled release capsules.
When oral acetazolamide administration is impractical,
similar doses of acetazolamide sodium may be given by
intramuscular or preferably by intravenous injection.
6.1 Absorption by route of exposure
Acetazolamide is well absorbed from the gastrointestinal
tract. Following oral administration of 500 mg of acetazolamide
as tablets, peak plasma concentrations are achieved within 1-3
hours. Low concentrations of acetazolamide are present in
plasma 24 hours after the drug is given.
6.2 Distribution by route of exposure
Acetazolamide is distributed throughout body tissues; it
concentrates principally in erythrocytes, plasma and kidneys
and to a lesser extent in liver, muscles, eyes and the central
nervous system. Acetazolamide does not accumulate in tissues.
The drug crosses the placenta in unknown quantities (Wade,
Acetazolamide is tightly bound to carbonic anhydrase and high
concentrations are present in tissues containing this enzyme
such as erythrocytes and the renal cortex (Reynolds, 1993).
There is a small amount of irreversible binding to red cells.
It is 70 to 90% bound to plasma protein (Dollery, 1991).
The volume of distribution of acetazolamide is 0.2 L/kg
6.3 Biological half-life by route of exposure
Different sources have quoted different plasma half-life
values for acetazolamide as follows 3 to 6 hours according to
Reynolds (1993) whilst Dollery (1991) quotes the plasma half
life range as 6 to 9 hours with a mean plasma half-life of 8
Acetazolamide is not metabolized (Dollery, 1991)
6.5 Elimination by route of exposure
Acetazolamide is excreted unchanged by the kidneys via
tubular secretion and passive reabsorption. After
administration of the oral tablets 70-100% (average 90%) of the
dose is excreted in urine within 24-hours; 47% of the dose is
excreted within 24 hours following administration of the
controlled release tablets.
There is no evidence of enterohepatic circulation although
small amounts of unchanged drug are eliminated in the bile
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
Metabolic acidosis may occur with long term
acetazolamide therapy due to reduced bicarbonate
concentrations, and in some instances, elevated plasma
Renal calculi have occurred, possibly due to the reduced
excretion of citrate combined with unchanged or
increased calcium excretion.
Acetazolamide is a carbonic anhydrase inhibitor.
Acetazolamide reduces the formation of hydrogen and
bicarbonate ions from carbon dioxide and water by
noncompetitive, reversible inhibition of the enzyme
carbonic anhydrase, thereby reducing the availability of
these ions for active transport into secretions.
In the eye acetazolamide reduces the formation of
aqueous humor so that intraocular pressure in both
normal and glaucomatous eyes is reduced.
In the kidney the inhibition of carbonic anhydrase
causes a reduction in hydrogen ion concentration in the
renal tubules so that there is as increased excretion of
bicarbonate and, to a lesser extent, sodium and
potassium. Potassium loss is particularly high during
acute administration. As the reabsorption of water is
reduced, the volume of urine is increased, and the pH
of the urine becomes alkaline. The excretion of
lithium is increased whereas the excretion of ammonia,
acidity, citrate and uric acid is decreased.
The anticonvulsant activity of acetazolamide has been
theorised to be caused by the production of metabolic
acidosis. However, it has been postulated that a direct
effect on carbonic anhydrase in the brain may result in
increased carbon dioxide tension, which has been
demonstrated to retard neuronal conduction; an
adrenergic mechanism may be involved (McEvoy, 1995).
For acute mountain sickness, possible mechanisms of
action include increased respiratory drive secondary to
induction of metabolic acidosis, and therapeutic effects
through diuresis (USP DI, 1995).
7.2.1 Human data
One patient died of cholestatic
jaundice after taking 13 g of acetazolamide in
26 days. In one patient, fatal bone marrow
depression with leukopenia, thrombocytopenia,
and anemia occurred after therapy with 500 mg
of acetazolamide twice daily for 14 weeks. One
case of renal failure (anuria) occurred in a
patient after taking 500 mg of acetazolamide
twice daily for 2 weeks (McEvoy, 1995).
According to Dollery (1991) intentional
overdose has not been reported. Drowsiness and
disorientation have been reported when daily
doses of 1 g and 5 g have been given to
patients with hepatic failure (Dollery,
7.2.2 Relevant animal data
Numerous animal studies have demonstrated that
the toxicity of acetazolamide was very low in the
species studied (mouse, dog, rat, monkey). In the mouse,
the LD50 is 3000 to 6000 mg/kg (Dollery, 1991)
7.2.3 Relevant in vitro data
No data available
There have been no reports of congenital defects despite
past widespread use though one women on 750 mg per day for
glaucoma during the 1st and 2nd trimester had a baby with a
sacrococcygeal teratoma but no causal link could be made
(Briggs et al, 1994).
Teratogenicity tests in rats and mice showed the absence of
fourth and fifth digits from the right forelimb in the
offspring of rats and mice that received 0.6% acetazolamide in
the diet during pregnancy (Layton and Trelstad, 1965, and
Holmes and Trelstad, 1979, as quoted by Dollery, 1991). There
were no apparent lessions in the newborn of rabbits and monkeys
(Scott et al, 1981, as quoted by Dollery, 1991).
The drug crosses the placenta in unknown quantities (Reynolds,
No data available
Potentially hazardous interactions
The effects of folic acid antagonists, oral hypoglycaemic
agents and oral anticoagulants may be increased by
The urinary antiseptic effect of methenamine may be prevented
by acetazolamide by keeping the urine alkaline. The
alkalinization of the urine by acetazolamide can reduce the
urinary excretion of many weak bases (including amphetamine,
quinine, quinidine, and diethylcarbamazine) and thus enhance
their pharmacological effects. In one patient taking phenytoin
and acetazolamide drug-induced osteomalacia was reported
(Davidson, 1975, Rawlins, 1978, Richens, 1977, and Mallov,
1977, as quoted by Dollery, 1991).
Potentially useful interactions
Acetazolamide can aid the penetration of weakly acidic
substances across the blood/cerebrospinal fluid barrier by
diffusion. Acetazolamide and other carbonic anhydrase
inhibitors increase the effects of mercurial diuretics
7.7 Main adverse effects
The incidence and severity of many adverse reactions to
acetazolamide are dose related and usually respond to a
lowering of the dosage or withdrawal of the drug.
Potentially life-threatening effects
Acetazolamide is a sulfonamide derivative, and some adverse
effects similar to those of sulfonamides have been reported.
The more serious effects include blood disorders, skin toxicity
and renal stone formation. Stevens-Johnson syndrome has not
been reported (Rubenstein, 1975, as quoted by Dollery,
Symptomatic adverse effects
Flushing, thirst, headache, drowsiness, dizziness, fatigue,
irritability, excitement, paresthesias, ataxia, hyperpnoea and
gastrointestinal disturbances have all been reported (Dollery,
Interference with clinical pathology tests
Sulfonamides may give false negative or decreased values for
urinary phenolsulfonphthalein and phenol red elimination values
for urinary protein, serum non-protein and for serum uric acid
9.0 CLINICAL EFFECTS
9.1 Acute poisoning
Oral ingestion is the usual means of exposure
outside of a health care facility. The clinical effects
are those described in Section 2.2.
9.1.3 Skin exposure
There is no appreciable dermal
9.1.4 Eye contact
There is no significant absorption or local
9.1.5 Parenteral exposure
Acetazolamide is used intravenously in acute
volume overload states or in acute glaucoma but would
not be available outside of a health care facility. The
clinical effects are those described in Section
9.2 Chronic poisoning
As in acute poisoning.
9.2.3 Skin exposure
As in acute poisoning.
9.2.4 Eye contact
As in acute poisoning.
9.2.5 Parenteral exposure
As in acute poisoning.
9.3 Course, prognosis, cause of death
The great majority of acute overdoses especially in
otherwise healthy individuals are benign and with simple
symptomatic care should have an excellent outcome. Patients
that are on chronic therapy and presenting with complications
thereof may have a worse prognosis especially if not suspected
by the clinician. Long-term therapy with diuretics must be
closely monitored. Patients on long-term therapy who present
with acute problems should be specifically evaluated for volume
status and electrolyte and acid-base abnormalities including
metabolic acidosis. Patients that present with arrhythmias or
seizures while on diuretics should be rapidly evaluated for
hyponatremia, hypokalemia, and hypomagnesemia. Patients that
present with unexplained fluid or electrolyte abnormalities
should be evaluated for possible diuretic abuse. Prognosis
should also be excellent in these patients if potential
abnormalities are rapidly evaluated and appropriately
Acetazolamide overdoses should be evaluated according to the
extent of volume depletion, the degree of electrolyte
abnormality or acid-base disturbance, and the severity of the
patient's underlying medical condition(s) and not according to
the amount ingested.
Deaths, though rare, do occur, not directly from the drug, but
complications in its use or abuse, namely arrhythmias and
seizures from electrolyte abnormalities or cardiac or renal
dysfunction secondary to volume depletion, or from severe
9.4 Systematic description of clinical effects
Arrhythmias may result from hypokalemia but are
usually not life-threatening unless digoxin is also
being administered and are self-limited with potassium
replenishment. Myocardial function may be impaired due
to hypovolemia in patients with marginal function who
require high ventricular loading pressures.
Chronic use may result in metabolic acidosis with a
compensatory hyperventilation that can lead to increased
pulmonary vascular resistance which is usually
reversible with discontinuation of the
Toxicity may be manifested as lethargy
and generalized weakness due to dehydration.
There may be seizures due to hyponatremia.
With chronic use, paresthesias and somnolence
are frequently reported (Goodman et al., 1990).
Headache, confusion, depression, irritability,
nervousness, vertigo, dizziness and ataxia have
been reported (McEvoy, 1995).
126.96.36.199 Peripheral nervous system
May demonstrate hyporeflexia due to
188.8.131.52 Autonomic nervous system
There are no known effects.
184.108.40.206 Skeletal and smooth muscle
There may be muscle weakness in both
skeletal and smooth muscle due to hypokalemia
and/or hypomagnesemia. Tremor and flaccid
paralysis have been reported (McEvoy,
Gastrointestinal disturbances including anorexia,
nausea, vomiting, diarrhea, constipation, and abdominal
distension may occur (McEvoy, 1995). Chronic use or
abuse may result in pancreatitis which may be immune-
Liver dysfunction has been reported as an
idiosyncratic reaction. A case of cholestatic jaundice
was reported after ingestion of 500 mg/day for 26 days
Incorrect or unmonitored use may
exacerbate underlying renal insufficiency due
to a multitude of conditions including diabetes
mellitus, chronic hypertension, cystic kidney
disease, collagen vascular disease, or gout.
Acetazolamide may cause nephrolithiasis and
renal colic (Ellenhorn, 1988). Dysuria and
crystalluria have been reported (McEvoy,
May lead to urinary incontinence in
the elderly and urinary retention in patients
9.4.7 Endocrine and reproductive systems
Hyperglycemia may result with acute or chronic
use or overdose and is usually self-limited.
No effects reported except allergic skin
9.4.9 Eye, ear, nose, throat: local effects
Acetazolamide is used to lower IOP in acute
glaucoma and also as a maintenance anti-glaucoma agent
and it works by inhibiting carbonic anhydrase in the
ciliary body. Myopia has been reported and generally
subsides with cessation of therapy (McEvoy,
There have been several case reports of fatal
aplastic anemia, and isolated agranulocytosis or
thrombocytopenia (Kristinsson, 1966).
220.127.116.11 Acid-base disturbances
Chronic use has resulted in a
hyperchloremic/hypokalemic metabolic acidosis
and can be seen to a lesser extent in an acute
ingestion. 41% of 27 elderly patients on
chronic therapy had moderate to severe acidosis
with serum pH less than 7.29 (Heller et al.,
18.104.22.168 Fluid and electrolyte disturbances
Acute or chronic use or abuse can
result in dehydration due to free water and
electrolyte loss. Hyponatremia, hypokalemia,
and hyperchloremia with bicarbonate loss may
occur. To a lesser degree and usually on a
more chronic basis, significant hypomagnesemia
and hypocalcemia may result.
Hyperuricemia and hyperlipidemia may
result following chronic use. Patients with
cirrhosis have experienced disorientation
possibly due to elevation of ammonia levels
with carbonic anhydrase inhibitors (McEvoy,
9.4.13 Allergic reactions
There have been several reports of skin rash and
serum sickness hypersensivity in patients on chronic
therapy (Kristinsson, 1966). Acetazolamide is a
sulfonamide derivative and shares the incidence of
hypersensitivity reactions (McEvoy, 1995). There are
rare true allergic reactions reported to
9.4.14 Other clinical effects
The resulting hypokalemia may exacerbate
underlying digoxin toxicity. There is a major potential
interaction with salicylates with documented cases with
significant increases in baseline salicylate levels when
acetazolamide was initiated in several elderly patients
(Sweeney et al, 1986). The toxicity would also be
exacerbated by metabolic acidosis induced by
acetazolamide, which will increase the CNS salicylate
level and resultant toxicity at a given salicylate serum
9.4.15 Special risks
As noted above special risks with furosemide use
or overdose exist in patients with pre-existing renal
disease or fluid and/or electrolyte abnormalities.
Acetazolamide is secreted in breast milk but in one case
a nursing infant exposed for one week showed no ill
results after receiving an estimated 0.6 mg/day
(approximately 0.06% of the maternal dose) (Briggs et
10.1 General principles
Since diuretic overdoses are usually benign, aggressive
decontamination procedures are not warranted. Treatment is
symptomatic in nature and is directed at correcting any fluid
and/or electrolyte abnormalities. More aggressive management
may be necessary in the patient with underlying abnormalities
including renal insufficiency, fluid and/or electrolyte
abnormalities, myocardial dysfunction, or taking other
potentially toxic medications such as digoxin or an
aminoglycoside antibiotic. Treatment aggressiveness must be
targeted to the severity of apparent toxicity and the
underlying chronicity thereof.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
Levels of diuretics are rarely available and
clinically useful, with the possible exception in
cases of alleged use or abuse in patients that present
with unexplained fluid and/or electrolyte
abnormalities or in suspected Munchausen or
Munchausen-by-proxy patients. There are acetazolamide
levels available at some research centers. There does
not appear to be any additional benefit in glaucoma
therapy with levels greater than 4.2 mg/ml and this is
usually achieved at a dose of 63 mg four times a day
at steady state (Friedland et al, 1977).
10.2.2 Biomedical analysis
Analysis should be targeted to the expected
electrolyte abnormalities including sodium, potassium,
chloride, and bicarbonate measurements in the mildly
to moderately ill patient. Blood gas analysis may be
necessary in the more severely ill patient or when one
needs to more precisely define the acid-base
disturbance that may be present. In more chronic use
or abuse, magnesium and calcium levels may be
necessary to define their depletion and need for
replenishment. If drug abuse of any kind is
suspected, a general urine drug screen may be
10.2.3 Toxicological analysis
Analysis would only be necessary as described
above. See Section 8 for additional detail.
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific treatment
Life supportive measures are usually not necessary and
may only be needed in potentially life-threatening
arrhythmias seen with hypokalemia (especially with concurrent
digoxin use) and with seizures secondary to hyponatremia,
both fairly rare complications. Symptomatic treatment is
directed at fluid/electrolyte repletion, initially with
intravenous isotonic crystalloid solutions. Depending on the
severity of volume depletion, this can be administered
initially as rapid boluses in the range of 1 - 2 L in the
adult patient or 10 - 20 mL/kg in the pediatric patient.
Further repletion should be based on clinical response to the
first bolus and definitive blood chemistry analysis. Care
must be taken in bolusing patients with underlying renal or
cardiac insufficiency that may make them more prone to fluid
overload and pulmonary edema.
In cases of severe hyponatremia resulting in seizures,
attention must be made to assess the patient's airway,
breathing, and circulation status. Seizure treatment should
follow standard guidelines.
Arrhythmias associated with hypokalemia usually are not
malignant and will respond to judicious potassium
replacement. If arrhythmias are malignant in nature and
while replenishing potassium, the usual ventricular
antiarrhythmic agents are utilized. In the chronic use or
abuse of diuretics, hypomagnesemia may contribute to
ventricular arrhythmias, especially torsade de pointe, and
replacement therapy in an urgent manner may terminate these
arrhythmias without resorting to potentially detrimental
medications. The dose would be magnesium sulfate 2 - 4 g
intravenously diluted to 100 - 250 mL over 15 - 30 minutes
(40 - 80 mg/kg for pediatric patients, suitably
Since these ingestions are usually benign or are
associated with hypovolemia, specific measures such as
inducing vomiting or administering cathartics are
contraindicated. If the patient presents early, certainly
less than 1 hour after ingestion, with a large ingestion or
with underlying cardiac, renal, or hepatic insufficiency,
then a dose of activated charcoal is probably indicated.
Certainly, in an otherwise normal child with a limited acute
ingestion, no GI decontamination is warranted.
There is no role for enhanced elimination, but a single
patient study with dialysis-dependent renal failure given one
500 mg dose of acetazolamide pre-dialysis showed an average
clearance of 22 mL/minute despite its high RBC distribution
(Vaziri et al, 1980).
10.6 Antidote treatment
There is no antidote for any of the
There is no antidote for any of the
10.7 Management discussion
Acetazolamide ingestions are usually benign and serious
complications rare. Treatment usually is limited to
supportive and symptomatic care.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
A 74 year-old woman on chronic acetazolamide therapy,
500 mg bid, for her glaucoma presented with abdominal pain,
anorexia, fatigue, and a 9 kg weight loss over 3 weeks. Her
heart rate was 140 per minute. Serum electrolytes were
sodium 138 mEq/L, potassium 3.8 mEq/L, chloride 118 mEq/L,
and bicarbonate 15 mEq/L. Arterial blood gases measurements
were: pH of 7.36, pO2 93 mmHg, and pCO2 26 mmHg. Her status
improved markedly with withdrawal of acetazolamide (Clark and
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
There are no specific antidotes.
12.2 Specific preventive measures
There are no specific preventive measures except
careful monitoring of patients on chronic therapy and
avoiding known drug interactions.
AHA (American Heart Association) (1992). Guidelines for
cardiopulmonary resuscitation and emergency cardiac care. JAMA.
268:2171 - 2302.
Antihypertensive drugs. In: Ellenhorn MJ & Barceloux DG, eds.
Medical toxicology: diagnosis and treatment of human poisoning.
New York, Elsevier, pp. 279-280.
Barkin RM, Rosen P, eds. (1990): Emergency pediatrics, 3rd ed.
St. Louis, Mosby.
Briggs GG, Freeman RK, Yaffe SJ (1994). Drugs in pregnancy and
lactation, 3rd ed. Baltimore, Williams &Wilkins, pp. 6-7.
Clark BG, Vestal RE (1984). Adverse drug reactions in the elderly:
Case studies. Geriatrics 39(12):53-66.
Dollery CT ed. (1991). Therapeutic drugs Edinburgh, Churchill
Ellenhorn MJ, Barceloux DG (1988). Medical Toxicology : Diagnosis
and Treatment of Human Poisoning. New York : Elsevier.
Friedland BR, Mallonee J, Anderson DR (1977). Short-term dose
response characteristics of acetazolamide in man. Arch Ophthalmol
Goodman L, Gilman AG, Rall TW, Nies AS, Taylor P, eds. (1985).
The pharmacological basis of therapeutics, 7th ed. New York,
Heller I, Halevy J, Cohen S, et al. (1985). Significant metabolic
acidosis induced by acetazolamide: not a rare complication. Arch
Intern Med 145:1815-1817.
Kristinsson A (1966). Fatal reaction to acetazolamide. Brit J
Lewin NA (1994). Antihypertensive agents. In: Goldfrank LR,
Weisman RS, Flomenbaum NE, Howland MA, Lewin NA, Hoffman RS.
Goldfrank's toxicologic emergencies 5th ed. Norwalk, Conn.,
Appleton & Lange, pp. 708.
Reynolds JEF, ed. (1993). Martindale: The Extra Pharmacopoeia.
Ass. editors Perfitt K, Parsons AN, Sweetman SC. London, The
McEvoy GK ed. (1995). American Hospital Formulary Service, Drug
information. Bethesda, MD, American Society of Hospital
Moffat AC(1986) Clarke's Isolation and identification of drugs in
pharmaceuticals, body fluids, and post-mortem material. 2nd ed.
(consulting editors Jackson JV, Moss MS, Widdop B) London,
Spratt DI, Pont A (1982). The clinical features of covert
diuretic use. West J Med. 137:331-335.
Sweeney KR, Chapron DJ, Brandt JL, Gomolin IH, Feig PU, Kramer PA
(1986). Toxic interaction between acetazolamide and salicylate:
case reports and a pharmacokinetic explanation. Clin Pharmacol
USP DI (1995). United States Pharmacopeia. 15th edition,
Rockville, MD, The United States Pharmacopeial Convention Inc.,
Vol. 1, p 659.
Vaziri ND< Saiki J, Barton CH, Rajudin M, Ness RL (1980).
Hemodialyzability of acetazolamide. Southern Medical Journal.
Woo OF (1994). Diuretics. In: Olson KR, ed. Poisoning and
overdose handbook. Norwalk, Conn., Appleton & Lange, pp. 157-
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES),
Craig R. Warden, MD
Jefferey L. Burgess, MD
Washington Poison Center
155 NE 100th St., Suite 400
PIM panel, October 1995
10 October 1995