title: Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors.
abstract: BACKGROUND
  Carbonic anhydrase inhibitors (CAIs) of the sulfonamide and sulfamate type are clinically used drugs as diuretics, antiglaucoma, antiepileptic, antiobesity and anti-high altitude disease agents. Anticancer agents based on CAIs are also in clinical development for the management of hypoxic, metastatic tumors. Acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide are mainly used as antiglaucoma drugs, sulthiame, topiramate and zonisamide as antiepileptic/antiobesity agents, celecoxib and polmacoxib are dual carbonic anhydrase/cycloxygenase inhibitors. Girentuximab, a monoclonal antibody and SLC-0111, a sulfonamide inhibitor, are in clinical trials as anticancer agents.
  
  
  METHODS
  The drug interactions with many classes of pharmacological agents are reviewed. Some of these drugs, such as acetazolamide, topiramate and celecoxib show a large number of interactions with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, antiepileptics, immunosupressants, anticholinesterase drugs, β-blockers, anesthetics, oral contraceptives, anticancer agents, antifungals, anti-mycobacterials, lithium, metformin and clopidogrel.
  
  
  CONCLUSIONS
  The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high. There are also synergistic effects between CAIs and some NSAIDs, anticancer agents and benzodiazepines for the management of cystoid macular edema, some tumor types and neuropathic pain, respectively.
authors.affiliation: a Polo Scientifico, NEUROFARBA Department, Section of Pharmaceutical and Nutriceutical Sciences , Università degli Studi di Firenze , 50019 Sesto Fiorentino , Florence , Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D000068579:Celecoxib / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000075202:Contraindications; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D008704:Methazolamide / Q000627:therapeutic use; D010634:Phenobarbital / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013451:Sulfonic Acids / Q000627:therapeutic use; D013843:Thiazines / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D000077236:Topiramate; D000078305:Zonisamide; D000096926:Benzenesulfonamides
chemical_list: D000086:Acetazolamide; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D000911:Antibodies, Monoclonal; D000927:Anticonvulsants; D000970:Antineoplastic Agents; D001569:Benzodiazepines; D002257:Carbonic Anhydrase Inhibitors; D000068579:Celecoxib; D005632:Fructose; D007555:Isoxazoles; D008704:Methazolamide; D010634:Phenobarbital; D000077145:Sulfanilamide; D013424:Sulfanilamides; D013449:Sulfonamides; D013451:Sulfonic Acids; D013843:Thiazines; D013876:Thiophenes; D000077236:Topiramate; D000078305:Zonisamide; C106533:G250 monoclonal antibody; C000935:dichlorophenobarbital; C111827:brinzolamide; C062765:dorzolamide; C005741:sulfamic acid; C084593:sulthiame; D000096926:Benzenesulfonamides
keywords: acetazolamide; brinzolamide; carbonic anhydrase; celecoxib; dorzolamide; inhibitor; methazolamide; sultiame; topiramate; zonisamide