Diamox

Carbonic Anhydrase Inhibitors

Severe

seizures / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
hepatic encephalopathy / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
aplastic anemia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
renal tubular obstruction / Delayed / Incidence not known

Moderate

depression / Delayed / Incidence not known
confusion / Early / Incidence not known
ataxia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
glycosuria / Early / Incidence not known
jaundice / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
hemolysis / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
hyperchloremia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
crystalluria / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
myopia / Delayed / Incidence not known
melena / Delayed / Incidence not known

Mild

dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
fatigue / Early / Incidence not known
drowsiness / Early / Incidence not known
malaise / Early / Incidence not known
headache / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
fever / Early / Incidence not known
polyuria / Early / Incidence not known
diarrhea / Early / Incidence not known
anorexia / Delayed / Incidence not known
xerostomia / Early / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
dysgeusia / Early / Incidence not known
tinnitus / Delayed / Incidence not known
flushing / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
purpura / Delayed / Incidence not known

Diamox, Diamox Sequels

Rx

Carbonic anhydrase inhibitor
Used for the prophylaxis and treatment of altitude sickness and management of glaucoma, refractory seizures, heart failure related or drug-induced edema, metabolic alkalosis, and increase intracranial pressure due to pseudotumor cerebri
Sulfonamide derivative; rare, serious adverse reactions related to sulfonamides including bone marrow depression and hypersensitivity reactions are possible

For the treatment of glaucoma. For the adjunctive treatment of open-angle glaucoma. Oral dosage (regular-release tablets) Adults

250 mg PO given 1 to 4 times daily. Maintenance dosage should be titrated to response. The maximum dosage is 1 g/day.

Infants†, Children†, and Adolescents†

10 to 30 mg/kg/day PO (Max: 1,000 mg/day) given in 1 to 4 divided doses has been used in small studies of pediatric patients with glaucoma. Although acetazolamide appears to be a more potent ocular hypotensive agent than topical therapy, the authors of the available studies recommend its use when adequate reductions in IOP are not achieved with topical therapy due to the potential for serious adverse reactions. 13.3 to 30 mg/kg/day PO given once daily (Max: 1,000 mg/day) was added to topical therapy in a retrospective study of pediatric patients with glaucoma of various etiologies (n = 22, age 8 months to 15 years). The duration of acetazolamide therapy ranged from 6 to 31 days and resulted in a mean decrease in intraocular pressure (IOP) of 29.6%. A target dose of approximately 10 mg/kg/day PO given in 2 to 4 divided doses was used in a crossover study of pediatric patients with glaucoma of various etiologies being switched from acetazolamide to topical dorzolamide (n = 11, age 3 to 12 years). The mean IOP in patients receiving acetazolamide was significantly reduced compared to baseline (36%, p less than 0.01); the mean IOP in patients receiving dorzolamide was also significantly reduced compared to baseline (27%, p less than 0.01) but to a lesser degree than in those patients treated with acetazolamide.

Oral dosage (extended-release capsules) Adults

500 mg PO twice daily. The maximum dosage is 1 g/day.

Children and Adolescents 12 years and older

500 mg PO twice daily. Doses greater than 1,000 mg/day are not usually associated with an increased effect.

Intravenous dosage Adults

500 mg IV for acute lowering of IOP or in patients unable to take the oral dosage. If needed, may repeat the dose in 2 to 4 hours.

For the treatment of secondary glaucoma and pre-operatively for acute angle-closure glaucoma. Oral dosage (regular-release tablets only)

NOTE: Sequels are a sustained-release dosage form and are not appropriate for acute treatment of angle-closure glaucoma.

Adults

250 mg PO every 4 hours. Alternately, treatment of some acute types of glaucoma has been initiated with a dose of 500 mg, followed by 125 to 250 mg PO every 4 hours.

Intravenous dosage Adults

500 mg IV for acute lowering of IOP or in patients unable to take the oral dosage. If needed, may repeat the dose in 2 to 4 hours.

For use as an adjunctive agent in the treatment of seizures including absence seizures, tonic-clonic seizures, and partial seizures.
NOTE: The extended release preparation is not recommended for use as an anticonvulsant.
Oral dosage (regular-release tablets only) Adults

8 to 30 mg/kg/day PO, given in up to 4 divided doses. The usual maintenance dosage is 375 to 1,000 mg/day.

Children† and Adolescents†

4 to 30 mg/kg/day PO given in up to 4 divided doses has been recommended. The usual maintenance dosage is 375 to 1,000 mg/day. Although higher doses have been used, several authors state that additional benefits are not seen at doses higher than 16 mg/kg/day or 1,000 mg/day. 10 mg/kg/day PO once daily was added to current anticonvulsant therapy in a study of pediatric patients with refractory seizure disorders (n = 37, age 1 to 17 years). The dose was increased up to 20 mg/kg/day PO based on clinical response and adverse reactions. The mean maintenance dose at the time of assessment of effectiveness was 12.2 +/- 4.2 mg/kg/day. Complete seizure control for more than 3 years was observed in 4 patients (10.8%), seizure recurrence after remission for 6 months was observed in 5 patients (13.5%), and a reduction of at least 50% in seizure frequency for more than 6 months was observed in 6 patients (16.2%). Acetazolamide was not effective in 22 patients (59.5%). The extended release preparation is not recommended for use as an anticonvulsant.

Intravenous dosage Adults

8 to 30 mg/kg/day IV, given in up to 4 divided doses. The usual maintenance dosage is 375 to 1,000 mg/day.

Children† and Adolescents†

8 to 30 mg/kg/day IV given in up to 4 divided doses. The usual maintenance dosage is 375 to 1,000 mg/day. Although higher doses have been used, several authors state that additional benefits are not seen at doses higher than 1,000 mg/day.

For the treatment of acute altitude sickness. Oral dosage (immediate-release) Adults

250 mg PO every 12 hours until symptoms resolve. May use in combination with dexamethasone for high altitude cerebral edema.  The FDA-approved dose is 500 to 1,000 mg/day PO in divided doses.

Infants†, Children†, and Adolescents†

2.5 mg/kg/dose (Max: 250 mg/dose) PO every 8 to 12 hours until symptoms resolve. May use in combination with dexamethasone for high altitude cerebral edema.

Oral dosage (extended-release) Adults

500 to 1,000 mg/day PO in divided doses.

Children and Adolescents 12 to 17 years

500 to 1,000 mg/day PO in divided doses.

For altitude sickness prophylaxis, including prevention of high altitude cerebral edema. Oral dosage (immediate-release) Adults weighing 100 kg or less

125 mg PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated. Prophylactic medications should be considered in addition to slow ascent for moderate- to high-risk situations.  The FDA-approved dose is 500 to 1,000 mg/day PO in divided doses starting 24 to 48 hours before ascent and continuing for 48 hours while at high altitude, or longer as necessary to control symptoms. In circumstances of rapid ascent (e.g., rescue or military operations), 1,000 mg/day PO in divided doses is recommended.

Adults weighing more than 100 kg

250 mg PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated. Prophylactic medications should be considered in addition to slow ascent for moderate- to high-risk situations.  The FDA-approved dose is 500 to 1,000 mg/day PO in divided doses starting 24 to 48 hours before ascent and continuing for 48 hours while at high altitude, or longer as necessary to control symptoms. In circumstances of rapid ascent (e.g., rescue or military operations), 1,000 mg/day PO in divided doses is recommended.

Infants†, Children†, and Adolescents†

2.5 mg/kg/dose (Max: 125 mg/dose) PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated.  Prophylactic medications are not routinely recommended for pediatric patients; slow ascent is preferred. If a rapid ascent is unavoidable or the patient is at high risk of developing altitude sickness, acetazolamide use may be warranted.

Oral dosage (extended-release) Adults

500 to 1,000 mg/day PO in divided doses starting 24 to 48 hours before ascent and continuing for 48 hours while at high altitude, or longer as necessary to control symptoms. In circumstances of rapid ascent (e.g., rescue or military operations), 1,000 mg/day PO in divided doses is recommended. While these doses are effective at preventing altitude sickness, they are not recommended due to association with more frequent and/or increased side effects in the absence of greater efficacy.

Children and Adolescents 12 to 17 years

500 to 1,000 mg/day PO in divided doses starting 24 to 48 hours before ascent and continuing for 48 hours while at high altitude, or longer as necessary to control symptoms. In circumstances of rapid ascent (e.g., rescue or military operations), 1,000 mg/day PO in divided doses is recommended. While these doses are effective at preventing altitude sickness, they are not recommended due to association with more frequent and/or increased side effects in the absence of greater efficacy.

For the treatment of edema due to heart failure or drug therapy. For the treatment of drug-induced edema. Oral dosage (immediate-release) Adults

250 to 375 mg PO once daily for 1 to 2 days, alternating with a day of rest.

Intravenous dosage Adults

250 to 375 mg IV once daily for 1 to 2 days, alternating with a day of rest.

For the treatment of edema due to heart failure. Oral dosage (immediate-release) Adults

5 mg/kg/dose or 250 to 375 mg PO once daily. If response to therapy decreases after an initial response, administer on alternate days, or for 2 days alternating with a day of rest to allow for kidney recovery.

Intravenous dosage Adults

500 mg IV once daily in combination with IV loop diuretic. The FDA-approved dose is 5 mg/kg/dose or 250 to 375 mg IV once daily. If response to therapy decreases after an initial response, administer on alternate days, or for 2 days alternating with a day of rest to allow for kidney recovery.

For use as an adjunctive agent to reverse metabolic alkalosis†.
NOTE: Appropriate correction of underlying fluid and electrolyte imbalances (e.g., administration of saline fluids, potassium chloride) should be instituted prior to acetazolamide administration. In patients with excessive carbon dioxide retention (e.g., COPD), reversal of metabolic alkalosis may assist the process of weaning from mechanical ventilation, by reducing compensatory carbon dioxide retention.
In mechanically ventilated adults. Intravenous dosage Adults

Correct underlying fluid and electrolyte imbalances. If metabolic alkalosis persists, a single dose of 500 mg IV may reverse non-chloride-responsive metabolic alkalosis in critically ill, mechanically ventilated patients. Similar results may be obtained with administration of 4 doses of 250 mg IV, given every 6 hours (total of 1,000 mg).

In pediatric patients. Intravenous dosage Adolescents

Dosing information is not available; however, a dose of 5 mg/kg/dose IV given 1 to 4 times per day has been recommended in children and a single dose of 500 mg IV or 250 mg IV every 6 hours for a total of 4 doses has been recommended in adults.

Infants and Children

3 to 5 mg/kg/dose IV given 1 to 4 times per day has been recommended based on the results of 3 retrospective studies. 3 to 5 mg/kg/dose IV every 6 hours was used in a study of neonates and infants with metabolic alkalosis due to chronic respiratory insufficiency (n = 89, age 30 to 65 weeks, gestational age 23 to 41 weeks). After 24 hours of acetazolamide, significant decreases were seen in mean serum HCO3 (29.5 mEq/L vs. 26.9 mEq/L, p less than 0.001) and base excess (10 mEq/L vs. 4 mEq/L, p less than 0.001). A mean dose of 4.98 +/- 1.14 mg/kg/dose given IV or PO every 6 to 8 hours for 3 to 24 doses was used in a study of critically ill pediatric patients (n = 34, age 18 days to 12 years) with metabolic alkalosis (pH greater than 7.45 and HCO3 greater than 26 mEq/L). Ten patients (29.4%) achieved treatment success defined as a serum HCO3 concentration of 22 to 26 mEq/L. Statistically significant decreases were seen in pre- and post-acetazolamide pH (7.51 vs. 7.37, p less than 0.001) and HCO3 (39.4 mEq/L vs 31.4 mEq/L, p less than 0.001). A dose of 5 mg/kg/dose IV or PO once daily for 3 days was used in a study of pediatric patients with heart disease and hypochloremic metabolic alkalosis (n = 28, age 10 days to 20 months). Significant differences compared to baseline were seen in serum HCO3 (36.2 mEq/L vs. 30.9 mEq/L, p less than 0.001), serum Cl (91.1 mEq/L vs. 95.4 mEq/L, p less than 0.03), acid-base excess (10.6 vs. 6.6, p less than 0.002), and pH (7.44 vs. 7.41, p less than 0.05). Significant changes in urine output were not seen at 8 or 24 hours after administration of acetazolamide.

Neonates

3 to 5 mg/kg/dose IV given 1 to 4 times per day has been recommended based on the results of 3 retrospective studies. A dose of 3 to 5 mg/kg/dose IV every 6 hours was used in a study of neonates and infants with metabolic alkalosis due to chronic respiratory insufficiency (n = 89, age 30 to 65 weeks, gestational age 23 to 41 weeks). After 24 hours of acetazolamide, significant decreases were seen in mean serum HCO3 (29.5 mEq/L vs. 26.9 mEq/L, p less than 0.001) and base excess (10 mEq/L vs. 4 mEq/L, p less than 0.001).

Oral dosage Infants and Children

5 mg/kg/dose PO given 1 to 4 times per day has been recommended based on the results of 2 retrospective studies. A mean dose of 4.98 +/- 1.14 mg/kg/dose given IV or PO every 6 to 8 hours for 3 to 24 doses was used in a study of critically ill pediatric patients (n = 34, age 18 days to 12 years) with metabolic alkalosis (pH greater than 7.45 and HCO3 greater than 26 mEq/L). Ten patients (29.4%) achieved treatment success defined as a serum HCO3 concentration of 22 to 26 mEq/L. Statistically significant decreases were seen in pre- and post-acetazolamide pH (7.51 vs. 7.37, p less than 0.001) and HCO3 (39.4 mEq/L vs 31.4 mEq/L, p less than 0.001). A dose of 5 mg/kg/dose IV or PO once daily for 3 days was used in a study of pediatric patients with heart disease and hypochloremic metabolic alkalosis (n = 28, age 10 days to 20 months). Significant differences compared to baseline were seen in serum HCO3 (36.2 mEq/L vs. 30.9 mEq/L, p less than 0.011), serum Cl (91.1 mEq/L vs. 95.4 mEq/L, p less than 0.03), acid-base excess (10.6 vs. 6.6, p less than 0.002), and pH (7.44 vs. 7.41, p less than 0.05). Significant changes in urine output were not seen at 8 or 24 hours after administration of acetazolamide.

Neonates

5 mg/kg/dose PO given 1 to 4 times per day has been recommended based on retrospective studies.

For use in urinary alkalinization†. Intravenous dosage Adults

5 mg/kg IV, may be repeated 2 or 3 times daily as needed to maintain an alkaline diuresis.

For the treatment of familial periodic paralysis†. Oral dosage (regular-release tablets) Adults

250 to 375 mg/day PO given in divided doses.

Geriatric

Consider dosage reduction. An elderly patient is more likely to develop hyperchloremic metabolic acidosis in addition to an age-related renal impairment.

For the treatment of central vestibular nystagmus†. Oral dosage (immediate-release tablets) Adults

Initially, 250 mg PO once daily. Increase dosage by 250 mg every 3 days, not to exceed a maximum of 3 g/day in divided doses. It is advisable to individualize the dosage based upon clinical response and tolerability.

For the treatment of increased intracranial pressure† due to pseudotumor cerebri or idiopathic intracranial hypertension. In pediatric patients. Oral dosage Infants, Children, and Adolescents

15 to 25 mg/kg/day PO given in 2 to 3 divided doses has been recommended. Some authors recommend increasing the dose by 25 mg/kg/day to a maximum of 100 mg/kg/day (Max: 2,000 mg/day) if necessary to achieve a clinical response. Continue acetazolamide until symptoms such as headache, disc swelling, and visual field abnormalities resolve (typically 3 to 9 months). Response rates to acetazolamide of 33% to 83% have been reported in several small retrospective studies in pediatric patients (n = 12 to 42, age 9 months to 17 years).

In adult patients. Oral dosage Adults

Initially, 500 mg PO twice daily. Increase dosage by 250 mg/week up to 4 g/day PO. If unable to tolerate, gradually decrease dosage to minimum of 125 mg/day PO.

†Indicates off-label use

Hepatic Impairment

Specific dosing recommendations for patients with hepatic impairment are not available. Acetazolamide is contraindicated in cases of marked liver disease or dysfunction and in patients with cirrhosis because of the risk of development of hepatic encephalopathy and electrolyte imbalance.

Renal Impairment

Specific guidelines for dosage adjustment in pediatric patients with renal impairment are not available. The following recommendations have been made for adult patients with renal impairment based on an initial dose of 250 mg IV/PO every 6 hours :
CrCl greater than 50 mL/min: Dosing interval every 6 hours for IV or regular-release tablets. No dosage guidelines are available for extended-release capsules.
CrCl 10 to 50 mL/min: Dosing interval every 12 hours for IV or regular-release tablets. No dosage guidelines are available for extended-release capsules.
CrCl less than 10 mL/min: Avoid use. Acetazolamide is contraindicated in marked kidney disease or dysfunction.
 
Intermittent hemodialysis Contraindicated in patients with severe renal disease; may potentiate acidosis and may cause CNS adverse effects in dialysis patients.
 
Continuous renal replacement therapy (CRRT) Dosing interval every 12 hours for IV or regular-release tablets. No dosage guidelines are available for extended-release capsules.

Acarbose: (Minor) Acetazolamide has rarely caused hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to drug-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between acetazolamide and all antidiabetic agents, such as acarbose. Diabetic patients should be monitored for a loss of blood glucose control.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Acetaminophen; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Acrivastine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Albuterol: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
Albuterol; Budesonide: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
Alogliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Alogliptin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Alogliptin; Pioglitazone: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Alprazolam: (Moderate) Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects of either agent.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
Amobarbital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Amoxapine: (Major) Cyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. In addition, pharmacokinetic interactions may occur. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Amphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Amphetamine; Dextroamphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Amphotericin B lipid complex (ABLC): (Moderate) Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
Amphotericin B liposomal (LAmB): (Moderate) Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
Amphotericin B: (Moderate) Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
Arsenic Trioxide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with arsenic trioxide.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation via calcium phosphate supersaturation.
Atracurium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Barbiturates: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Benzphetamine: (Moderate) Urinary alkalinizers, such as acetazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations. Urinary alkalinizers increase the proportion of non-ionized metabolites of the amphetamine molecule, resulting in decreased renal excretion of these compounds. Alkaline urine will significantly increase the half-life of benzphetamine.
Brompheniramine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Bumetanide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Bupropion: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together.
Bupropion; Naltrexone: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together.
Butabarbital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Butalbital; Acetaminophen: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Butalbital; Acetaminophen; Caffeine: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as carbonic anhydrase inhibitors may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Canagliflozin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Carbamazepine: (Minor) Acetazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine. Potential mechanisms for this interaction include an acetazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolic acidosis.
Central-acting adrenergic agents: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cetirizine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Chlorpheniramine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Chlorpropamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Ciprofloxacin: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity.
Cisapride: (Major) Cisapride should be used with great caution in patients receiving potassium-wasting diuretic therapies, including carbonic anhydrase inhibitors. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias. Serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed prior to administration of cisapride and whenever conditions develop that may affect electrolyte imbalance or renal function. Cisapride is contraindicated for use in patients with known serum electrolyte imbalances; cisapride should be discontinued if such imbalances occur.
Cisatracurium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Citalopram: (Moderate) Caution is advisable during concurrent use of citalopram and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with citalopram.
Clozapine: (Moderate) Caution is advisable during concurrent use of clozapine and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with clozapine.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Corticosteroids: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Cyclosporine: (Minor) Acetazolamide may increase serum cyclosporine concentrations. If cyclosporine and acetazolamide are to be coadministered, monitor the patient for cyclosporine toxicity.
Dapagliflozin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Dapagliflozin; Saxagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Desloratadine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Dextroamphetamine: (Moderate) Monitor for an increase in the incidence and severity of amphetamine-related adverse effects during concomitant use of urinary alkalinizing agents. Increasing urine pH may increase amphetamine exposure by reducing urinary excretion of amphetamine. A urine pH more than 7.5 has been observed to increase the half-life of amphetamine from 8 to 10.5 hours to 16 to 31 hours when compared to a pH less than 6. Additionally, a urine pH more than 8 has been observed to reduce the amount of amphetamine excreted in the urine over 16 hours to less than 3% of the original dose; a 5-fold reduction compared to controls.
Dextromethorphan; Bupropion: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Dextromethorphan; Quinidine: (Major) Acetazolamide can decrease excretion of quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of quinidine can be prolonged or enhanced.
Dichlorphenamide: (Major) Use dichlorphenamide and acetazolamide, another carbonic anhydrase inhibitor, together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diflunisal: (Moderate) The concomitant use of diflunisal and acetazolamide has resulted in a significant decrease in intraocular pressure due to increased concentrations of acetazolamide. If diflunisal and acetazolamide are used concurrently, monitor the patient for signs and symptoms of toxicity; reduced drug dosages may be needed.
Digoxin: (Moderate) Carbonic anhydrase inhibitors can result in hypokalemia. Patients receiving these drugs concurrently with cardiac glycosides are at an increased risk for digitalis toxicity if hypokalemia develops during treatment. Ventricular irritability may occur. Monitor for hypokalemia and supplement with potassium if needed.
Donepezil; Memantine: (Moderate) Systemic carbonic anhydrous inhibitors have the potential to increase urine pH, and potentially reduce the renal clearance of memantine. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Increases in urinary pH may decrease elimination of memantine, resulting in drug accumulation and potential toxicity.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with other agents that may lead to electrolyte abnormalities, such as carbonic anhydrase inhibitors, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
Empagliflozin; Linagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Empagliflozin; Linagliptin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Empagliflozin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Ephedrine: (Major) Acetazolamide or methazolamide can decrease excretion and enhance the effects of ephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized ephedrine available for renal tubular reabsorption. If concurrent use cannot be avoided, monitor for the appearance of ephedrine-related toxicity.
Ephedrine; Guaifenesin: (Major) Acetazolamide or methazolamide can decrease excretion and enhance the effects of ephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized ephedrine available for renal tubular reabsorption. If concurrent use cannot be avoided, monitor for the appearance of ephedrine-related toxicity.
Epoprostenol: (Moderate) Further reductions in blood pressure may occur when epoprostenol is administered with other antihypertensive agents.
Ertugliflozin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Ertugliflozin; Sitagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Ethacrynic Acid: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Ethotoin: (Minor) Acetazolamide or methazolamide can induce osteomalacia in patients being concomitantly treated with hydantoin anticonvulsants. The carbonic anhydrase inhibitors increase the rate of urinary calcium excretion; phenytoin increases the metabolism of the D vitamins. When combined, the effects on bone catabolism can be additive.
Fexofenadine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Flecainide: (Moderate) Carbonic anhydrase inhibitors can decrease the urinary excretion and enhance the clinical effects of flecainide. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption into the systemic circulation.
Fosphenytoin: (Minor) Acetazolamide or methazolamide can induce osteomalacia in patients being concomitantly treated with hydantoin anticonvulsants. The carbonic anhydrase inhibitors increase the rate of urinary calcium excretion; phenytoin increases the metabolism of the D vitamins. When combined, the effects on bone catabolism can be additive.
Furosemide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Glimepiride: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Glipizide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Glipizide; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Glyburide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Glyburide; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Guaifenesin; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol.
Hydantoins: (Minor) Acetazolamide or methazolamide can induce osteomalacia in patients being concomitantly treated with hydantoin anticonvulsants. The carbonic anhydrase inhibitors increase the rate of urinary calcium excretion; phenytoin increases the metabolism of the D vitamins. When combined, the effects on bone catabolism can be additive.
Hydrocodone; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as acetazolamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Ibuprofen; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Incretin Mimetics: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Insulins: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Ipratropium; Albuterol: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
Levalbuterol: (Moderate) Albuterol may cause additive hypokalemia when coadministered with carbonic anhydrase inhibitors. These combinations can lead to symptomatic hypokalemia and associated ECG changes in some susceptible individuals. Monitoring of potassium levels would be advisable.
Linagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Linagliptin; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Lisdexamfetamine: (Moderate) Urinary alkalinizers, such as acetazolamide and methazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations. Urinary alkalinizers increase the proportion of non-ionized metabolites of the amphetamine molecule, resulting in decreased renal excretion of these compounds. Alkaline urine will significantly increase the half-life of lisdexamfetamine.
Lithium: (Moderate) Carbonic anhydrase inhibitors interfere with lithium reabsorption at the proximal tubule, the primary site of lithium reabsorption. Thus, lithium serum concentrations are likely to decrease during administration of carbonic anhydrase inhibitors. In one small study evaluating the pharmacokinetic effects of several different medications on a single 600 mg dose of lithium carbonate, administration of acetazolamide resulted in a 31% increase in lithium clearance. If carbonic anhydrase inhibitor therapy is needed during lithium administration, monitoring of lithium concentrations is recommended, along with clinical monitoring for evidence of a decrease in lithium efficacy. Patients should promptly report persistent changes in moods or behaviors.
Loop diuretics: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Loratadine; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Magnesium Hydroxide: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
Magnesium Salts: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia. (Minor) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
Mannitol: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Mecamylamine: (Major) Acetazolamide can decrease excretion of mecamylamine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of mecamylamine can be prolonged or enhanced.
Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Memantine: (Moderate) Systemic carbonic anhydrous inhibitors have the potential to increase urine pH, and potentially reduce the renal clearance of memantine. The clearance of memantine is reduced by about 80% under alkaline urine conditions at pH 8. Increases in urinary pH may decrease elimination of memantine, resulting in drug accumulation and potential toxicity.
Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Metformin; Repaglinide: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Acetazolamide has rarely caused hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to drug-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between acetazolamide and repaglinide. Diabetic patients should be monitored for a loss of blood glucose control.
Metformin; Rosiglitazone: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Metformin; Saxagliptin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Metformin; Sitagliptin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Methadone: (Moderate) Carbonic anhydrase inhibitors can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed.
Methamphetamine: (Moderate) Urinary alkalinizers, such as acetazolamide, result in decreased renal excretion of amphetamines. Monitor for amphetamine-related side effects. Avoid concomitant use in amphetamine overdose situations. Urinary alkalinizers increase the proportion of non-ionized metabolites of the amphetamine molecule, resulting in decreased renal excretion of these compounds. Alkaline urine will significantly increase the half-life of methamphetamine.
Methazolamide: (Contraindicated) The combination of acetazolamide and methazolamide would constitute duplicate therapy. Additive hypokalemic effects may occur with if two carbonic anhydrase inhibitors are coadministered.
Methenamine: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Acid Phosphate: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methenamine; Sodium Salicylate: (Major) The therapeutic action of methenamine requires an acidic urine. Acetazolamide can alkalinize the urine, thereby decreasing the effectiveness of methenamine. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form; concurrent use of methenamine and urinary alkalizers is not recommended.
Methohexital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Mexiletine: (Major) If acidifying or alkalinizing agents, such as carbonic anhydrase inhibitors, are administered concomitantly with mexiletine, urinary excretion and plasma half-life of the antiarrhythmic can be altered. Elimination of mexiletine is decreased when the urine is alkaline and increased when it is acidic. Dosage adjustments should be made as necessary.
Miglitol: (Minor) Acetazolamide has rarely caused hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to drug-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between acetazolamide and miglitol. Diabetic patients should be monitored for a loss of blood glucose control.
Mivacurium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Naproxen; Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Nateglinide: (Minor) Acetazolamide has rarely caused hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to drug-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between acetazolamide and all antidiabetic agents, such as nateglinide. Diabetic patients should be monitored for a loss of blood glucose control.
Nifedipine: (Moderate) Nifedipine can have additive hypotensive effects with other antihypertensive agents (including carbonic anhydrase inhibitors). This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Nitrates: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
Omeprazole; Sodium Bicarbonate: (Minor) Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation via calcium phosphate supersaturation.
Pancuronium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Pentobarbital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Phenobarbital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Phentermine; Topiramate: (Major) Avoid concurrent use of acetazolamide or methazolamide with topiramate. Topiramate is a weak carbonic anhydrase inhibitor. Concomitant use of topiramate with acetazolamide or methazolamide may create a physiological environment that increases the risk of renal stone formation associated with topiramate use. Additionally, through an additive effect, the use of topiramate with agents that may increase the risk for heat-related disorders (acetazolamide and methazolamide), may lead to oligohidrosis, hyperthermia and heat stroke.
Phenytoin: (Minor) Acetazolamide or methazolamide can induce osteomalacia in patients being concomitantly treated with hydantoin anticonvulsants. The carbonic anhydrase inhibitors increase the rate of urinary calcium excretion; phenytoin increases the metabolism of the D vitamins. When combined, the effects on bone catabolism can be additive.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT pr

olongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Pioglitazone: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Pioglitazone; Glimepiride: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Pioglitazone; Metformin: (Moderate) Carbonic anhydrase inhibitors such as acetazolamide frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of acetazolamide with metformin may increase the risk for lactic acidosis; consider more frequent monitoring. Carbonic anhydrase inhibitors may also alter blood sugar; both hyperglycemia and hypoglycemia have been described. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction. (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Potassium-sparing diuretics: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Pramlintide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Primidone: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
Pseudoephedrine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Pseudoephedrine; Triprolidine: (Moderate) Acetazolamide and methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if acetazolamide or methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Quetiapine: (Moderate) Caution is advisable during concurrent use of quetiapine and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
Quinidine: (Major) Acetazolamide can decrease excretion of quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of quinidine can be prolonged or enhanced.
Quinine: (Moderate) Use caution if using carbonic anhydrase inhibitors and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Repaglinide: (Minor) Acetazolamide has rarely caused hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to drug-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between acetazolamide and repaglinide. Diabetic patients should be monitored for a loss of blood glucose control.
Rocuronium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Rosiglitazone: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Salicylates: (Major) Avoid the coadministration of high-dose salicylates and carbonic anhydrase inhibitors whenever possible. There were reports of anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death with high-dose aspirin and acetazolamide. Two mechanisms could cause increased acetazolamide concentrations, resulting in CNS depression and metabolic acidosis: first, competition with aspirin for renal tubular secretion and, second, displacement by salicylates from plasma protein binding sites. Additionally, carbonic anhydrase inhibitors alkalinize urine and increase the excretion of normal doses of salicylates; decreased plasma salicylate concentrations may or may not be clinically significant.
Saxagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Secobarbital: (Minor) Acetazolamide can induce osteomalacia in patients treated chronically with barbiturates. Potential mechanisms for this interaction include a carbonic anhydrase inhibitor induced increase in the urinary excretion of calcium and an increase in barbiturate effects resulting from metabolic acidosis. Acetazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates.
SGLT2 Inhibitors: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Sitagliptin: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Sodium Bicarbonate: (Minor) Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation via calcium phosphate supersaturation.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as carbonic anhydrase inhibitors may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Minor) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia.
Sotalol: (Major) Diuretics should be used cautiously with sotalol and should be accompanied by close monitoring of electrolyte balance because hypokalemia and hypomagnesemia have been associated with an increased risk of proarrhythmia.
Succinylcholine: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Sulfonylureas: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Thiazide diuretics: (Moderate) Acetazolamide promotes electrolyte excretion including hydrogen ions, sodium, and potassium. It can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Thiazolidinediones: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Tolazamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Tolbutamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Topiramate: (Major) Avoid concurrent use of acetazolamide or methazolamide with topiramate. Topiramate is a weak carbonic anhydrase inhibitor. Concomitant use of topiramate with acetazolamide or methazolamide may create a physiological environment that increases the risk of renal stone formation associated with topiramate use. Additionally, through an additive effect, the use of topiramate with agents that may increase the risk for heat-related disorders (acetazolamide and methazolamide), may lead to oligohidrosis, hyperthermia and heat stroke.
Torsemide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Trazodone: (Moderate) Trazodone can lower the seizure threshold of anticonvulsants, although the overall risk is low at therapeutic doses. Patients may require increased concentrations of anticonvulsants to achieve equivalent effects if trazodone is added.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Urea: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
Vecuronium: (Moderate) Nondepolarizing neuromuscular blockers when combined with carbonic anhydrase inhibitors may lead to prolonged respiratory depression. This action is due to enhanced neural blockade as a result of potential hypokalemia from the carbonic anhydrase inhibitor. Serum potassium concentrations should be checked and adjusted prior to the administration of nondepolarizing neuromuscular blockers.
Vorinostat: (Moderate) Use vorinostat and carbonic anhydrase inhibitors together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Carbonic anhydrase inhibitors increase the excretion of some electrolytes including potassium; electrolyte abnormalities such as hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Zonisamide: (Moderate) Monitor for the appearance or worsening of metabolic acidosis if zonisamide is given concomitantly with other carbonic anhydrase inhibitors. Concomitant use of zonisamide with another carbonic anhydrase inhibitor may increase the severity of metabolic acidosis and may also increase the risks of hyperammonemia, encephalopathy, and kidney stone formation. Monitor serum ammonia concentrations if signs or symptoms of encephalopathy occur. Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued and may resolve or decrease in severity with a decrease of the daily dose.

Acetazolamide/Acetazolamide Sodium/Diamox Intravenous Inj Pwd F/Sol: 500mg
Acetazolamide/Diamox Oral Tab: 125mg, 250mg
Acetazolamide/Diamox/Diamox Sequels Oral Cap ER: 500mg

Adults

1,000 mg/day PO/IV is the FDA-approved max; up to 4,000 mg/day PO has been used off-label.

Geriatric

1,000 mg/day PO/IV is the FDA-approved max; up to 4,000 mg/day PO has been used off-label.

Adolescents

Safety and efficacy have not been established for the regular-release tablets or injection; maximum dose recommendations vary depending on the indication. 1,000 mg/day PO is the FDA-approved max dose for the extended-release capsule. The following max doses have been used off-label for the regular-release tablet and/or injection: for the management of glaucoma and seizures, up to 30 mg/kg/day PO (Max: 1,000 mg/day); for the reversal of metabolic alkalosis, up to 20 mg/kg/day IV/PO (Max: 1000 mg/day); for the prevention and treatment of altitude sickness, up to 5 mg/kg/day PO (Max: 250 mg/day) and 7.5 mg/kg/day PO (Max: 750 mg/day), respectively; for the treatment of pseudotumor cerebri, up to 100 mg/kg/day PO (Max: 2,000 mg/day).

Children

Children 12 years: Safety and efficacy have not been established for the regular-release tablets or injection; maximum dose recommendations vary depending on the indication. 1,000 mg/day PO is the FDA-approved max dose for the extended-release capsule. The following max doses have been used off-label for the regular-release tablet and/or injection: for the management of glaucoma and seizures, up to 30 mg/kg/day PO (Max: 1,000 mg/day); for the reversal of metabolic alkalosis, up to 20 mg/kg/day IV/PO; for the prevention and treatment of altitude sickness, up to 5 mg/kg/day PO (Max: 250 mg/day) and 7.5 mg/kg/day PO (Max: 750 mg/day), respectively; for the treatment of pseudotumor cerebri, up to 100 mg/kg/day PO (Max: 2,000 mg/day).
Children 1 to 11 years: Safety and efficacy have not been established; maximum dose recommendations vary depending on the indication. For the management of glaucoma and seizures, doses up to 30 mg/kg/day PO (Max: 1,000 mg/day) have been used. For the reversal of metabolic alkalosis, doses up to 20 mg/kg/day IV/PO have been used. For the prevention and treatment of altitude sickness, doses up to 5 mg/kg/day PO (Max: 250 mg/day) and 7.5 mg/kg/day PO (Max: 750 mg/day), respectively, have been recommended. For the treatment of pseudotumor cerebri, doses up to 100 mg/kg/day PO (Max: 2,000 mg/day) have been used.

Infants

Safety and efficacy have not been established; maximum dose recommendations vary depending on the indication. For the management of glaucoma, doses up to 30 mg/kg/day PO have been used. For the reversal of metabolic alkalosis, doses up to 20 mg/kg/day IV/PO have been used. For the prevention and treatment of altitude sickness doses up to 5 mg/kg/day PO and 7.5 mg/kg/day PO, respectively, have been recommended. For the treatment of pseudotumor cerebri, doses up to 100 mg/kg/day PO have been used.

Neonates

Safety and efficacy have not been established; however, doses up to 20 mg/kg/day IV/PO have been used off-label for the reversal of metabolic alkalosis.

Mechanism of Action: Carbonic anhydrase is an enzyme responsible for forming hydrogen and bicarbonate ions from carbon dioxide and water. By inhibiting this enzyme, acetazolamide reduces the availability of these ions for active transport. Hydrogen ion concentrations in the renal tubule lumen are reduced by acetazolamide, leading to an alkaline urine and an increased excretion of bicarbonate, sodium, potassium, and water. A reduction in plasma bicarbonate results in metabolic acidosis, which rapidly reverses the diuretic effect. Reduced intraocular pressure (IOP) is the result of a 50—60% reduction in aqueous humor production by acetazolamide and is likely due to decreased bicarbonate ion concentrations in ocular fluid.The anticonvulsant activity of acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which increases carbon dioxide tension and inhibits neuronal transmission. The successful treatment of altitude sickness involves production of respiratory and metabolic acidosis, which increases ventilation and binding of oxygen to hemoglobin. This occurs because the drug decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension.

Acetazolamide is available for oral and intravenous administration; intramuscular administration is not recommended. Acetazolamide is approximately 90% bound to plasma proteins and is widely distributed, especially to those tissues where the carbonic anhydrase enzyme is present in high concentrations (e.g., renal cortex and erythrocytes). Acetazolamide is not metabolized and is eliminated renally via both active tubular secretion and passive reabsorption.

Oral Route

Acetazolamide is rapidly absorbed from the GI tract, and peak serum concentrations for the tablets and extended-release capsules are achieved in 2—4 hours and 8—12 hours, respectively. When used for glaucoma, the onset of action for the tablets is about 1.5—2 hours, and the peak effect on IOP is achieved within 2—12 hours, depending on the formulation used. The half-life of the tablets is 10—15 hours. Following administration of the tablet preparation, 90—100% of a dose is excreted within 24 hours. Approximately 47% of an extended-release dose is eliminated renally within 24 hours.

Intravenous Route

The onset of action following IV administration of acetazolamide is about 2 minutes, reaching a peak effect in 15 minutes and lasting 4—5 hours. Acetazolamide is eliminated renally. Following administration of the IV preparation, 90—100% of a dose is excreted within 24 hours.

Intramuscular Route

The intramuscular route of administration is not recommended due to the alkalinity of the injection, which causes pain. Data regarding the pharmacokinetics specific to intramuscular administration are not available, but the duration of action is expected to be similar to the intravenous route. Acetazolamide is eliminated renally, with 90—100% of a parenteral dose excreted within 24 hours.

Pregnancy

There are no adequate and well-controlled studies on acetazolamide therapy in pregnancy. Acetazolamide has been shown to be teratogenic (defects in the limbs) to hamsters, mice, rabbits, and rats following both oral and parenteral administration. Published data on the risk of acetazolamide therapy during pregnancy are unclear. There have been case reports of neonatal sacrocoocygeal teratoma, metabolic acidosis, hypocalcemia, hypomagnesemia, renal tubular acidosis, and low birth weight following in utero exposure to acetazolamide. Other reports did not identify any adverse fetal effects or increased risk to the infant. Acetazolamide should only be used if the benefit justifies the potential risk to the fetus. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to acetazolamide; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.

According to the manufacturer, because of the potential for adverse reactions in nursing infants from acetazolamide, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother. Following 4 to 5 days of acetazolamide extended-release capsules 500 mg twice daily (started on postpartum day 6), a mother's breast milk concentration was 1.3 to 2.1 mcg/mL and her maternal plasma concentration was 5.2 to 6.4 mcg/mL; both levels were drawn 1 to 7 hours after an acetazolamide dose. Infant plasma levels were 0.2 to 0.6 mcg/mL at 2 to 12 hours after breast-feeding. The infant did not experience any adverse effects; however, breast-feeding was discontinued after 1 week. In a report of 2 newborns experiencing metabolic acidosis following in utero exposure to acetazolamide 500 mg three times daily, the maternal breast milk acetazolamide concentration was 4.2 mcg/mL 1 to 3 days after birth. The metabolic acidosis resolved in both newborns despite continued breast-feeding. However, content experts and the American Academy of Pediatrics consider acetazolamide to be usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.