Acetazolamide

Chloroprocaine should not be used when sulfonamide drugs are being employed. The para-aminobenzoic acid metabolite of chloroprocaine inhibits sulfonamide action.

Concomitant use with other carbonic anhydrase inhibitors is not advisable due to possible additive effects.

Patients receiving sulfonamides generally should not be treated with Mecamylamine HCl (ganglion blocker).

Methenamine mandelate should not be administered concurrently with sulfonamides due to insoluble precipitate formation in acid urine.

Should not be administered concomitantly due to possibility of augmented phototoxicity as sulfonamides are known photosensitizers.

See WARNINGS section for detailed interaction information.

Carbonic anhydrase inhibitor that may increase risk of lactic acidosis by decreasing serum bicarbonate and inducing metabolic acidosis.

Phototoxic agents that may cause severe phototoxic skin reaction (severe sunburn). Avoid for 24 hours before and after ALA administration.

Urinary alkalinizing agent that decreases amphetamine excretion by increasing non-ionized species, elevating blood levels and potentiating action.

Increased risk of methemoglobinemia when concurrently exposed to articaine.

Increased risk of developing methemoglobinemia when concurrently exposed to this antibiotic class.

Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide and toxicity due to renal tubule secretion competition.

Concurrent use can lead to high serum concentrations of acetazolamide and toxicity due to competition at renal tubule for secretion.

Concurrent use can lead to high serum acetazolamide concentrations and toxicity due to competition for renal tubule secretion.

Increased risk of methemoglobinemia when concurrently exposed to this antibiotic oxidizing agent with local anesthetics.

Increased risk of methemoglobinemia when local anesthetics are used concomitantly with antibiotics.

Increased risk of methemoglobinemia when concurrently exposed with bupivacaine.

Carbonic anhydrase inhibitor that may increase risk for lactic acidosis when used concomitantly.

Drugs that induce methemoglobinemia; concomitant use may increase risk for developing methemoglobinemia.

Concomitant use may increase risk of developing methemoglobinemia. Monitor closely.

Antibiotics associated with increased methemoglobinemia risk when used with ropivacaine.

Urinary alkalinizing agent that increases blood levels and potentiates amphetamine action. Co-administration should be avoided.

Urinary alkalinizing agent increases blood levels and potentiates amphetamine action, increasing risk of adverse effects.

Acetazolamide causes decreased serum bicarbonate and metabolic acidosis; concomitant use may increase risk of lactic acidosis.

Acetazolamide causes decreased serum bicarbonate and metabolic acidosis; concomitant use with TRIJARDY XR may increase risk of lactic acidosis.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk of lactic acidosis when used with SYNJARDY or SYNJARDY XR.

Increases risk of lactic acidosis due to decreased serum bicarbonate and metabolic acidosis when used with metformin.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk for lactic acidosis when used with glyburide and metformin hydrochloride.

Increased risk of methemoglobinemia when used concurrently with lidocaine.

Antibiotic class that may cause methemoglobinemia when used concomitantly with lidocaine patch 5%.

Antibiotic that increases risk of methemoglobinemia when used concurrently with lidocaine and capsaicin patch.

Antibiotic; increased risk of methemoglobinemia when concurrently exposed.

Increased risk of methemoglobinemia when used concurrently with lidocaine hydrochloride.

Antibiotic associated with increased methemoglobinemia risk when used concurrently.

Increased risk of methemoglobinemia when lidocaine is used concurrently with these antibiotic oxidizing agents.

Concurrent exposure increases risk of methemoglobinemia in patients administered local anesthetics.

Increased risk of methemoglobinemia; antibiotics associated with methemoglobinemia when used with local anesthetics.

Increased risk of methemoglobinemia when used with lidocaine.

Increased risk of methemoglobinemia when lidocaine is concurrently exposed to antibiotics.

Increased risk of methemoglobinemia when local anesthetics are concurrently exposed to antibiotics.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and induces metabolic acidosis, increasing risk of lactic acidosis with linagliptin and metformin.

Increased risk of methemoglobinemia when concurrently exposed to antibiotics.

Concurrent exposure increases risk of methemoglobinemia in patients administered mepivacaine.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and induces metabolic acidosis, increasing risk for lactic acidosis when used with metformin.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk of lactic acidosis with metformin.

Carbonic anhydrase inhibitor that may increase risk of lactic acidosis by decreasing serum bicarbonate and inducing metabolic acidosis.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk for lactic acidosis when used with metformin.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk for lactic acidosis when used with metformin.

These drugs may precipitate with formaldehyde in the urine, increasing the danger of crystalluria.

May precipitate with formaldehyde in urine, increasing the danger of crystalluria.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Hepatotoxic products Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

Concurrent use with aspirin can lead to high serum acetazolamide concentrations and toxicity due to competition at renal tubule for secretion.

Increased risk of methemoglobinemia when penicillin is concurrently administered with sulfonamides (antibiotics).

Carbonic anhydrase inhibitor decreases serum bicarbonate and increases lactic acidosis risk with metformin. Requires more frequent monitoring.

Increased risk of methemoglobinemia when prilocaine is concurrently exposed to sulfonamides.

Increased risk of methemoglobinemia when used concurrently with prilocaine.

Concomitant use may increase risk of bone marrow suppression and folate deficiency.

Increased risk of developing methemoglobinemia when concurrently exposed to sulfonamides.

Carbonic anhydrase inhibitor causing metabolic acidosis. Concomitant use may increase risk of metformin-associated lactic acidosis.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and induces metabolic acidosis, increasing risk for lactic acidosis when used with JANUMET.

Concurrent use with acetazolamide increases the risk of renal calculus formation.

Methotrexate Avoid concurrent use Sulfonamides can also displace methotrexate from plasma protein binding sites and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations. Oral Hypoglycemics Monitor blood glucose more frequently Like other sulfonamide-containing drugs, BACTRIM potentiates the effect of oral hypoglycemic that are metabolized by CYP2C8 (e.g., pioglitazone, repaglinide, and rosiglitazone) or CYP2C9 (e.g., glipizide and glyburide) or eliminated renally via OCT2 (e.g., metformin).

Concurrent use as carbonic anhydrase inhibitor may increase severity of metabolic acidosis and increase risk of kidney stone formation.

Increased risk of methemoglobinemia when concurrently exposed.

Increased risk of methemoglobinemia when used concurrently with triethanolamine salicylate.

Increased risk of methemoglobinemia when used with Trubrexa Transdermal Patch.

These drugs may precipitate with formaldehyde in the urine, increasing the danger of crystalluria.

Concomitant carbonic anhydrase inhibitor use may increase severity of metabolic acidosis and risk of kidney stone formation or hyperammonemia. Monitor for metabolic acidosis worsening.

Drug Interactions Aspirin - See WARNINGS Acetazolamide modifies phenytoin metabolism with increased serum levels of phenytoin. By decreasing the gastrointestinal absorption of primidone, acetazolamide may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing, or changing the dose of acetazolamide in patients receiving primidone.

Acetazolamide modifies phenytoin metabolism with increased serum levels of phenytoin. By decreasing the gastrointestinal absorption of primidone, acetazolamide may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing, or changing the dose of acetazolamide in patients receiving primidone.

Acetazolamide may increase or decrease blood glucose levels. Consideration should be taken in patients receiving antidiabetic agents.

Sulfonamides may interfere with bactericidal effects of amoxicillin, though clinical significance is not well documented.

Acetazolamide decreases urinary excretion of amphetamine, potentially enhancing magnitude and duration of effect.

May interfere with the bactericidal effect of ampicillin.

Bromocriptine may increase the unbound fraction of highly protein-bound sulfonamides, potentially altering their effectiveness and risk for side effects.

May increase risk of methemoglobinemia when concurrently exposed with bupivacaine.

Increased risk of methemoglobinemia when concurrently exposed.

Increased risk of developing methemoglobinemia when concurrently exposed.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk for lactic acidosis when used with INVOKAMET. Consider more frequent monitoring.

CYP3A4 inhibitor that increases carbamazepine plasma levels. Close monitoring of carbamazepine levels and dosage adjustment may be required.

Acetazolamide may elevate cyclosporine levels.

Urinary alkalinizing agent increases non-ionized amphetamine concentration and decreases urinary excretion, potentiating effects.

Acetazolamide may increase the effects of other folic acid antagonists.

May potentiate hypoglycemic action of glyburide; patient should be closely observed for hypoglycemia.

Highly protein-bound drugs that may increase glucose-lowering effect of glimepiride, increasing susceptibility to hypoglycemia.

Sulfonamides may potentiate hypoglycemic action of glipizide. Patient should be observed closely for hypoglycemia when initiated or withdrawn.

Sulfonamides may potentiate the hypoglycemic action of glipizide. Patient should be observed closely for hypoglycemia.

Carbonic anhydrase inhibitor that decreases serum bicarbonate and may increase risk for lactic acidosis with glyburide-metformin.

May decrease thyroid hormone secretion, which may result in hypothyroidism when used with levothyroxine.

Antibiotic class that increases risk of methemoglobinemia when used concomitantly with lidocaine and tetracaine.

Acetazolamide increases lithium excretion, potentially decreasing lithium levels.

Examples: metronidazole Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents Clinical Impact: Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion. Examples: acetazolamide, theophylline, sodium bicarbonate Methyldopa, Phenytoin and Carbamazepine Clinical Impact: Concomitant use may increase risk of toxic effects of these drugs Intervention: Monitor patients closely for symptoms of toxicity of methyldopa, phenytoin, and carbamazepine.

Can lower serum lithium concentrations by increasing urinary lithium excretion. Recommend frequent monitoring and dosage adjustment.

Increased risk of methemoglobinemia when concurrently exposed to antibiotics with bupivacaine.

Acetazolamide may prevent the urinary antiseptic effect of methenamine.

Bacteriostatic antibacterial may antagonize the bactericidal effect of penicillin and may compete for renal tubular secretion. Concurrent use should be avoided.

Bacteriostatic antibiotic may antagonize bactericidal effect of penicillin; also competes for renal tubular secretion and prolongs penicillin serum half-life.

May antagonize the bactericidal effect of penicillin and may compete for renal tubular secretion. Concurrent use should be avoided.

Acetazolamide modifies phenytoin metabolism increasing serum levels, which may increase osteomalacia occurrence in patients on chronic therapy.

Concomitant use may increase the risk of photosensitivity reaction. Avoid concomitant use with other photosensitizing agents.

Acetazolamide decreases gastrointestinal absorption of primidone, reducing serum concentrations and potentially decreasing anticonvulsant effect.

Probenecid significantly increases total sulfonamide plasma levels by decreasing renal excretion of conjugated sulfonamides; monitor plasma concentrations during prolonged coadministration.

Probenecid decreases renal excretion of conjugated sulfonamides, significantly increasing total sulfonamide plasma levels; monitor concentrations during prolonged coadministration.

Acetazolamide reduces urinary excretion of quinidine and may enhance its effect.

Other photosensitizing agents that could increase the potential for skin photosensitivity reactions.

May interfere with the bactericidal effects of penicillin in vitro; clinical significance is not well documented.

Examples: Acetazolamide, methazolamide Methotrexate Clinical Impact: Aspirin may enhance the toxicity of methotrexate by displacing it from its plasma protein binding sites and/or reducing its renal clearance.

Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).

Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. Drugs that may increase the risk of hypoglycemia: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).

Table 5: Clinically Significant Drug Interactions with TRESIBA Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors.

Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

Table 6: Clinically Significant Drug Interactions with LEVEMIR Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors.

7 DRUG INTERACTIONS Table 6 includes clinically significant drug interactions with BASAGLAR Table 6: Clinically Significant Drug Interactions with BASAGLAR Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).

Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics.

Table 8: Clinically Significant Drug Interactions with REZVOGLAR Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics.

Table 8: Clinically Significant Drug Interactions with Insulin Glargine-yfgn Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors.

7 DRUG INTERACTIONS Table 6: Clinically Significant Drug Interactions with APIDRA Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.

7 DRUG INTERACTIONS Table 1: Clinically Significant Drug Interactions with HUMULIN N Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when HUMULIN N is co-administered with these drugs.

Table 2: Clinically Significant Drug Interactions with ADMELOG Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).

Clinically Significant Drug Interactions with LYUMJEV Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics.

Intervention: Patients simultaneously receiving naproxen tablets or naproxen sodium tablets and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.

Intervention: Patients simultaneously receiving naproxen oral suspension and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.

Intervention: Patients simultaneously receiving naproxen sodium and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.

7.4 Drugs Affecting Glucose Metabolism The following are examples of medications that may increase the susceptibility to hypoglycemia when administered with SYMLIN: anti-diabetic products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics.

Urinary alkalizers (acetazolamide, sodium bicarbonate) Urinary alkalinizing agents may increase plasma quinine concentrations.

Urinary Alkalizers (Acetazolamide, Sodium Bicarbonate) Urinary alkalinizing agents may increase plasma quinine concentrations.

Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide Intervention: Repaglinide dose increases and increased frequency of glucose monitoring may be required when co-­administered.

Drug Interactions Administration of a sulfonamide may increase the effect of oral anticoagulants and methotrexate, probably by displacement of these drugs from binding sites on plasma albumin. Conversely, agents such as indomethacin, probenecid and salicylates may displace sulfonamides from plasma albumin and increase the concentrations of free drug in plasma.

7 DRUG INTERACTIONS The table below presents clinically significant drug interactions with KIRSTY Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics ( 7 ).