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    Carbonic Anhydrase Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Carbonic anhydrase inhibitor; acetazolamide is used for high-altitude sickness, and as an adjunct treatment for glaucoma and epilepsy.

    COMMON BRAND NAMES

    Diamox, Diamox Sequels

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    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.

    Geriatric

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

    Children†

    8 to 30 mg/kg/day PO or 300 to 900 mg/m2/day, given in divided doses every 8 hours.

    Oral dosage (extended-release capsules)
    Adults

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

    Geriatric

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

    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.

    Geriatric

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

    Children†

    5 to 10 mg/kg IV every 6 hours for acute glaucoma. The maximum dosage is 1 g/day.

    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.

    Geriatric

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

    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.

    Geriatric

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

    Children†

    5 to 10 mg/kg IV every 6 hours for acute glaucoma. Maximum dosage is 1 g/day.

    For use as an alternative agent in the treatment of absence seizures.
    NOTE: The extended release preparation is not recommended for use as an anticonvulsant.
    Oral dosage (regular-release tablets only)
    Adults, Adolescents†, and Children†

    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.

    Geriatric

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

    Intravenous dosage
    Adults, Adolescents†, and Children†

    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.

    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 acute altitude sickness.
    Oral dosage
    Adults

    250 mg PO twice daily is recommended by clinical practice guidelines. Descent is the preferred initial treatment. When descent is not possible or effective, symptomatic treatment (e.g., analgesics and antiemetics), oxygen, and other treatments, including acetazolamide, should be considered. The FDA-approved dosage is 500 to 1,000 mg PO daily, in divided doses, for 48 hours while at high altitude or longer as necessary to control symptoms. In circumstances of rapid ascent, such as rescue or military operations, 1,000 mg PO daily, in divided doses, is recommended.

    Infants†, Children†, and Adolescents†

    2.5 mg/kg/dose PO every 8 to 12 hours (maximum: 250 mg/dose) is recommended by clinical practice guidelines. Descent is the preferred initial treatment, particularly for younger children and infants. When descent is not effective or not possible, symptomatic treatment (e.g., analgesics and antiemetics), oxygen, and other treatments, including acetazolamide, should be considered.

    For altitude sickness prophylaxis, including prevention of high altitude cerebral edema.
    Oral dosage
    Adults

    125 mg PO twice daily is recommended by clinical practice guidelines. Prophylactic medications should be considered in addition to slow ascent for moderate- to high-risk situations. Start prophylaxis with acetazolamide the day prior to ascent if possible; however, beneficial effects are still seen if started the day of ascent. Continue prophylaxis for 2 to 3 days after reaching the target altitude or until descent is initiated.. The FDA-approved dosage is 500 to 1,000 mg PO daily, in divided doses, beginning 24 to 48 hours before ascent and continuing for 48 hours while at high altitude. In circumstances of rapid ascent, such as rescue or military operations, 1,000 mg PO daily, in divided doses, is recommended. Although effective, higher prophylactic doses (i.e., 500 to 1,000 mg daily) may be associated with increased side effects such as paresthesias, urinary frequency, and dysgeusia.

    Infants†, Children†, and Adolescents†

    2.5 mg/kg/dose PO every 12 hours (maximum: 125 mg/dose) is recommended by clinical practice guidelines. 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, start prophylaxis with acetazolamide the day prior to ascent if possible; however, beneficial effects are still seen if started the day of ascent. Continue prophylaxis for 2 to 3 days after reaching the target altitude or until descent is initiated.

    For the treatment of edema secondary to congestive heart failure or drug therapy.
    Oral or Intravenous dosage
    Adults

    5 mg/kg or 250 to 375 mg PO/IV given in the morning. Give for 2 days and then allow 1 to 2 days drug-free or give on alternate days in order to maintain diuretic effect.

    Geriatric

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

    Children†

    5 mg/kg or 150 mg/m2 PO or IV given once daily.

    For use as an adjunctive agent to reverse metabolic alkalosis† in mechanically ventilated patients.
    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.
    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).

    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.

    Geriatric

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

    Children

    5 mg/kg IV, may be repeated 2 to 3 times daily if needed.

    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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1000 mg/day PO/IV.

    Geriatric

    1000 mg/day PO/IV.

    Adolescents

    Safety and efficacy have not been established; do not exceed the adult maximum dose of 1000 mg/day PO/IV.

    Children

    Safety and efficacy have not been established; do not exceed the adult maximum dose of 1000 mg/day PO/IV.

    Infants

    Safety and efficacy have not been established; however, doses up to 7.5 mg/kg/day PO have been used off-label for acute altitude sickness.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Acetazolamide is contraindicated in cases of marked liver disease or dysfunction. Acetazolamide is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy and electrolyte imbalance.

    Renal Impairment

    CrCl 50—80 mL/min: Dosing interval >= 6 hours for IV or regular-release tablets. No dosage guidelines are available for sustained-release capsules.
    CrCl 10—50 mL/min: Dosing interval >= 12 hours for IV or regular-release tablets. No dosage guidelines are available for sustained-release capsules.
    CrCl < 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.

    STORAGE

    Diamox:
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store reconstituted product in refrigerator (36 to 46 degrees F)
    - Use within 12 hours after reconstitution
    Diamox Sequels:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Increasing the dose of acetazolamide does not increase the diuresis and may increase the incidence of CNS adverse events. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.
     
    Acetazolamide can be used for treatment or prevention of high altitude sickness. Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide is used, it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral edema.
     
    Acetazolamide interferes with the high-performance liquid chromatography (HPLC) method of assay for theophylline. Interference with the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods.

    Carbonic anhydrase inhibitor hypersensitivity, sulfonamide hypersensitivity

    Acetazolamide is contraindicated in patients with a history of acetazolamide hypersensitivity and should be avoided in patients with a history of carbonic anhydrase inhibitor hypersensitivity. Acetazolamide is a chemical sulfonamide possessing a structure and pharmacologic activity distinct from the bacteriostatic sulfonamides. Rarely, sulfonamides of any type can produce allergic reactions, some of which may be severe. A case of anaphylactic shock (30 minutes following acetazolamide for cataract surgery) has been reported in a patient with documented sulfonamide hypersensitivity. While the risk of cross-sensitivity between acetazolamide and antibacterial sulfonamides appears low, acetazolamide should be discontinued in any person who exhibits reactions suggestive of sulfonamide hypersensitivity. Rare fatalities have occurred due to severe hypersensitivity reactions to sulfonamides (see Adverse Reactions). Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of acetazolamide.

    Hepatic disease

    Acetazolamide should be avoided in patients with marked hepatic disease; these patients are more susceptible to electrolyte and acid/base imbalance. In addition, patients with cirrhosis are at an increased risk for hepatic encephalopathy.

    Acid/base imbalance, acidemia, adrenal insufficiency, anuria, dialysis, electrolyte imbalance, hyperchloremia, hypokalemia, hyponatremia, metabolic acidosis, renal disease, renal failure, renal impairment

    Acetazolamide is contraindicated in patients with electrolyte imbalance (e.g., hyponatremia, hypokalemia, hyperchloremia), acid/base imbalance (metabolic acidosis, acidemia), or adrenal insufficiency. Acetazolamide is contraindicated in patients with severe renal disease (renal failure, anuria). Dosage reduction is warranted in patients with renal impairment. Acetazolamide may potentiate acidosis and cause neurologic side effects in dialysis patients. Plasma chloride levels and excretion of sodium and potassium are altered during treatment, and these conditions can be exacerbated by the renal and metabolic effects of the drug.

    Closed-angle glaucoma

    Long-term administration of acetazolamide is contraindicated in patients with closed-angle glaucoma as acetazolamide may allow closure of the angle to occur while lowered intraocular pressure masks the worsening glaucoma.

    Emphysema, infection, pulmonary disease, respiratory acidosis

    Patients with pulmonary disease, including those with pulmonary infection, obstruction, emphysema, or respiratory acidosis should be monitored closely during treatment with acetazolamide because of the potential for respiratory acidosis.

    Agranulocytosis, bone marrow suppression

    Acetazolamide, as with other sulfonamide derivatives, can induce bone marrow suppression, agranulocytosis, aplastic anemia, and other blood dyscrasias so precaution is advised for early detection of such reactions. If they occur, the drug should be discontinued and appropriate therapy instituted.

    Sunlight (UV) exposure

    Like other sulfonamide derivatives, photosensitivity may occur with carbonic anhydrase inhibitors including acetazolamide. Some patients may be more sensitive to sunlight (UV) exposure while receiving acetazolamide. Patients should avoid prolonged exposure to sunlight or sunlamps, and to follow appropriate sun precautions.

    Pregnancy

    Acetazolamide is classified as FDA pregnancy risk category C. Acetazolamide has been shown to be teratogenic (defects in the limbs) in animals. There are not adequate and well-controlled studies in pregnant women. Acetazolamide should only be used if the benefit justifies the potential risk to the fetus.

    Breast-feeding

    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. 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.

    Driving or operating machinery

    Some adverse reactions to acetazolamide, such as drowsiness, fatigue, and myopia may impair the ability for driving or operating machinery.

    Children, growth inhibition, infants, neonates

    Growth inhibition has been reported in pediatric patients receiving long-term acetazolamide therapy and is believed to occur secondary to chronic acidosis. Periodic monitoring of serum electrolytes is recommended. Monitor growth in neonates, infants, and children who present with acid-base imbalance on chronic maintenance therapy.

    Geriatric

    Geriatric patients may be more likely to develop hyperchloremic non-anion gap metabolic acidosis during treatment with acetazolamide; a reduced dosage may be needed due to an age-related decline in renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, some anticonvulsants may be used to treat disorders other than seizures. The need for indefinite continuation in treating any condition should be based on confirmation of the condition and its potential cause(s). Determining effectiveness and tolerability through evaluation of symptoms should be used to adjust doses. Therapeutic drug monitoring is not required or available for most anticonvulsants, including acetazolamide. Anticonvulsants may cause cause nausea/vomiting, dizziness, ataxia, somnolence/lethargy, incoordination, blurred or double vision, restlessness, toxic encephalopathy, anorexia, and headaches; these effects can increase the risk for falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

    ADVERSE REACTIONS

    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
    myopia / Delayed / Incidence not known
    growth inhibition / 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
    flushing / Rapid / Incidence not known
    injection site reaction / Rapid / Incidence not known
    tinnitus / Delayed / Incidence not known
    purpura / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acarbose: 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; Butalbital: 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.
    Acetaminophen; Butalbital; Caffeine: 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.
    Acetaminophen; Butalbital; Caffeine; Codeine: 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.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: 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: 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: 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.
    Acetohexamide: 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.
    Acrivastine; Pseudoephedrine: 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: 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; Ipratropium: 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: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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: Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects of either agent.
    Aluminum Hydroxide; Magnesium Hydroxide: 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: 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.
    Ammonium Chloride: Carbonic anhydrase inhibitors increase the risk of developing systemic acidosis if administered with ammonium chloride.
    Amobarbital: 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: 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: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amphetamine; Dextroamphetamine Salts: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amphetamine; Dextroamphetamine: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amphotericin B cholesteryl sulfate complex (ABCD): Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
    Amphotericin B lipid complex (ABLC): Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
    Amphotericin B liposomal (LAmB): Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
    Amphotericin B: Acetazolamide can potentiate hypokalemia and therefore can increase the risk of hypokalemia caused by amphotericin B.
    Arsenic Trioxide: Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities include acetazolamide. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms.
    Aspirin, ASA; Butalbital; Caffeine: 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; Butalbital; Caffeine; Codeine: 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.
    Atracurium: 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.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: 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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: 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.
    Barbiturates: 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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: 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: 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: Urinary alkalinizers, such as acetazolamide diminish the urinary excretion of amphetamines. Acetazolamide can increase the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of benzamphetamine will be prolonged in the presence of acetazolamide. This drug combination should be avoided, especially in amphetamine overdose situations.
    Brompheniramine; Hydrocodone; Pseudoephedrine: 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: 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: 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: 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: 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: 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 Carbonate; Magnesium Hydroxide: 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.
    Calcium Phosphate, Supersaturated: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function.
    Carbamazepine: 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.
    Carbetapentane; Pseudoephedrine: 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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: 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.
    Carbinoxamine; Pseudoephedrine: 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.
    Central-acting adrenergic agents: 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: 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: 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; Dihydrocodeine; Pseudoephedrine: 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; Guaifenesin; Hydrocodone; Pseudoephedrine: 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; Hydrocodone; Pseudoephedrine: 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: 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: 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: 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: 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: 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: Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and acetazolamide.
    Clozapine: Caution is advisable during concurrent use of clozapine and acetazolamide. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Concurrent use of clozapine and medications known to cause electrolyte imbalance may increase the risk of QT prolongation.
    Colesevelam: Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam.
    Corticosteroids: 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: Acetazolamide may increase serum cyclosporine concentrations. If cyclosporine and acetazolamide are to be coadministered, monitor the patient for cyclosporine toxicity.
    Dapagliflozin; Metformin: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function.
    Desloratadine; Pseudoephedrine: 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: 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: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: 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: 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: 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: 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: 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.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: 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.
    Donepezil; Memantine: 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.
    Doxacurium: 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.
    Droperidol: 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: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function.
    Ephedrine: 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: Further reductions in blood pressure may occur when epoprostenol is administered with other antihypertensive agents.
    Ethacrynic Acid: 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: 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: 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: 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: 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: 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.
    Gallium Ga 68 Dotatate: 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: 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.
    Glimepiride; Pioglitazone: 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. 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.
    Glimepiride; Rosiglitazone: 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. 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: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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; Hydrocodone; Pseudoephedrine: 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.
    Guaifenesin; Pseudoephedrine: 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.
    Halofantrine: Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided when feasible in those patients receiving potassium-wasting diuretic therapies including carbonic anhydrase inhibitors. Electrolyte imbalances may occur while on these diuretics, which may in turn predispose patients to the cardiac effects of halofantrine.
    Haloperidol: QT prolongation has been observed during haloperidol treatment. Use of haloperidol and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of haloperidol and acetazolamide.
    Hydantoins: 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; Potassium Guaiacolsulfonate; Pseudoephedrine: 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.
    Hydrocodone; Pseudoephedrine: 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: 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: 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: 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: Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
    Inamrinone: Hypokalemia may occur due to excessive diuresis during inamrinone therapy. Fluid and electrolyte changes and renal function should be carefully monitored during inamrinone therapy.
    Incretin Mimetics: 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: 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.
    Irinotecan: Volume depletion due to irinotecan-induced vomiting or diarrhea can be exacerbated by diuretics. Withholding diuretics during irinotecan dosing, especially during periods of active vomiting or diarrhea, may be desirable.
    Kava Kava, Piper methysticum: Any substances that act on the CNS, including anticonvulsants, may have a pharmacodynamic interaction with kava kava.
    Levalbuterol: 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.
    Levomethadyl: Acetazolamide can potentiate hypokalemia. Patients receiving acetazolamide concurrently with levomethadyl are at an increased risk for cardiac toxicity if hypokalemia develops during treatment.
    Linagliptin: 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: Concurrent use of amphetamines and urinary alkalinizers, such as acetazolamide and methazolamide, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some agents for blood pressure. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Alkalinizing medications should be avoided in amphetamine overdose.
    Lithium: 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: 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: 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: 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: 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. 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 Sulfate; Potassium Sulfate; Sodium Sulfate: 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: 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.
    Mefloquine: 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: 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.
    Mephobarbital: 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.
    Metformin: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function.
    Metformin; Pioglitazone: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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; Repaglinide: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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. Carbonic anhydrase inhibitors frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase. Monitor electrolytes and renal function. 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: 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: Avoid the concomitant use of acetazolamide and methamphetamine, especially in amphetamine overdose situations. Acetazolamide is a urinary alkalinizer and, thus, will diminish the urinary excretion of amphetamines. 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: The combination of acetazolamide and methazolamide would constitute duplicate therapy. Additive hypokalemic effects may occur with if two carbonic anhydrase inhibitors are coadministered.
    Methenamine: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Norfloxacin: Carbonic anhydrase inhibitors cause urine alkalinization and may promote crystalluria if coadministered with norfloxacin.
    Octreotide: 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: Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation via calcium phosphate supersaturation.
    Pancuronium: 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: 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: 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: 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: 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: Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Use of pimozide and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of pimozide and acetazolamide. According to the manufacturer, potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
    Pioglitazone: 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: 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: 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: 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: 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: QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance. Therefore, caution is advisable during concurrent use of quetiapine and acetazolamide.
    Quinidine: 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: Quinine and its metabolites are primarily excreted by the kidneys, and excretion is decreased when the urine is alkaline. Alkalinization of the urine by drugs such as acetazolamide and methazolamide can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Repaglinide: 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.
    Reserpine: The concomitant administration of reserpine with diuretics or other antihypertensive agents can result in additive hypotensive effects. This interaction may be desirable, but dosages should be adjusted accordingly.
    Rocuronium: 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: 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: 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: 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: 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: 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.
    Simvastatin; Sitagliptin: 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: 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: 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: 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.
    Sotalol: 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: 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: 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: 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: 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.
    Thiopental: 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.
    Tolazamide: 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: 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: Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Topiramate: 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: 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: 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: Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
    Tubocurarine: 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.
    Urea: 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: 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: 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.
    Warfarin: Per the prescribing information for warfarin sodium, concomitant use of carbonic anhydrase inhibitors (or other diuretics) and warfarin may result in an increased or decreased PT/INR. Patients should be monitored for changes in the INR when either of these drugs is initiated or discontinued, or if the dosage is changed.
    Ziconotide: Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
    Zonisamide: Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution with other drugs that may also predispose patients to heat-related disorders like carbonic anhydrase inhibitors.

    PREGNANCY AND LACTATION

    Pregnancy

    Acetazolamide is classified as FDA pregnancy risk category C. Acetazolamide has been shown to be teratogenic (defects in the limbs) in animals. There are not adequate and well-controlled studies in pregnant women. Acetazolamide should only be used if the benefit justifies the potential risk to the fetus.

    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. 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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.