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Table 4 Drug classes, precipitant and object drugs, mechanisms and recommendations for clinically significant pDDIs

From: Important drug classes associated with potential drug–drug interactions in critically ill patients: highlights for cardiothoracic intensivists

Drug classes Precipitant drugsa Object drugsa Mechanisms Recommendations
Anti-infective agents Itraconazole Tacrolimus Metabolism (inh) Monitor tacrolimus concentration
Diltiazem Metabolism (inh) Monitor diltiazem toxic effects
Digoxin Absorption Monitor digoxin concentration
Atorvastatin Metabolism (inh) Reduce dose, monitor toxic effects
Clarithromycin Metabolism (inh)b Monitor toxic effect of clarithromycin/itraconazole
Methylprednisolone Metabolism (inh) Reduce dose, monitor corticosteroid toxicity
Voriconazole Tacrolimus Metabolism (inh) Reduce dose, monitor tacrolimus concentration
Cyclosporine Metabolism (inh) Reduce dose, monitor cyclosporine concentration
Diltiazem Metabolism (inh) Monitor diltiazem toxic effects
Methylprednisolone Metabolism (inh) Reduce dose, monitor corticosteroid toxicity
Methadone Metabolism (inh) Monitor methadone toxic effects
Midazolam Metabolism (inh) Monitor midazolam toxic effects
Ciprofloxacin Theophylline Metabolism (inh) Reduce dose, monitor theophylline toxic effects
Erythromycin Additive Avoid combination
Formoterol Additive Avoid combination
Granisetron Additive Avoid combination
Voriconazole Additive Avoid combination
  Rifampin Itraconazole Metabolism (ind/inh)b Avoid combination/monitor for clinical response to itraconazole
Clarithromycin Metabolism (ind/inh)b Monitor for clarithromycin therapeutic effects/rifampin toxic effects
Cyclosporine Metabolism (ind) Consider an alternative, monitor cyclosporine serum concentrations
Midazolam Metabolism (ind) Monitor midazolam therapeutic effects
Dapsone Metabolism (ind) Monitor for dapsone therapeutic effects and methemoglobinemia
Erythromycin Amlodipine Metabolism (inh) Consider an alternative, monitor toxic effects
Carbamazepine Metabolism (inh) Consider an alternative, monitor toxic effects
Dexamethasone Metabolism (inh) Monitor corticosteroids toxic effects
Prednisolone Metabolism (inh) Monitor corticosteroids toxic effects
Posaconazole Midazolam Metabolism (inh) Consider an alternative, monitor toxic effects
Isoniazid Metoprolol Metabolism (inh) Consider an alternative, monitor response
Valganciclovir Lamivudine Additive Monitor hematologic toxicity
Clarithromycin Midazolam Metabolism (inh) Consider an alternative, monitor for toxic effects
Central nervous system agents Carbamazepine Phenytoin Metabolism (ind)b Monitor for phenytoin/carbamazepine serum concentrations
Clonazepam Metabolism (ind) Consider an alternative
Warfarin Metabolism (ind) Monitor therapeutic effects
Citalopram Metabolism (ind/inh)b Monitor citalopram therapeutic effects/carbamazepine toxic effects
Fluvoxamine Metabolism (ind/inh)b Monitor fluvoxamine therapeutic effects/carbamazepine toxic effects
  Imipramine Metoprolol Metabolism (inh) Consider an alternative, monitor response
Citalopram Metabolism (inh)b Consider an alternative, monitor toxic effects of imipramine/citalopram
Quetiapine fumarate Haloperidol Additive Avoid combination
Carbidopa and levodopa Antagonistic Consider an alternative
Phenytoin Amlodipine Metabolism (ind/inh)b Monitor amlodipine therapeutic effects/phenytoin toxicity
Indomethacin Acetylsalicylic acid Additive Monitor bleeding, avoid regular use of indomethacin
Cyclosporine Additive Consider an alternative, monitor nephrotoxicity
Furosemide Antagonistic Monitor therapeutic effect
Valproic acid Lorazpam Metabolism (inh) Monitor lorazepam toxic effects
Electrolytic, caloric, and water balance Sodium polystyrene sulfate Calcium carbonate Antagonistic Separate doses by 2 or more hours, monitor metabolic alkalosis
Zinc sulfate Ofloxacin Absorption Separate doses by 2 or more hours
Magnesium sulfate Ciprofloxacin Absorption Separate doses by 2 or more hours
Calcium carbonate Isoniazid Absorption Separate doses by 2 or more hours
Levofloxacin Absorption Separate doses by 2 or more hours
Mycophenolate Absorption Separate doses by 2 or more hours
Autonomic drugs Atracurium Methylprednisolone Additive Monitor neuromuscular adverse effects
Prednisolone Additive Monitor neuromuscular adverse effects
Dexamethasone Additive Monitor neuromuscular adverse effects
Hydrocortisone Additive Monitor neuromuscular adverse effects
Cisatracurium Prednisolone Additive Monitor neuromuscular adverse effects
Cardiovascular drugs Amiodarone Digoxin Excretion Reduce digoxin dosage, monitor serum concentration
Metoprolol Metabolism (inh) Consider an alternative, monitor response
Gemfibrozil Atorvastatin Metabolism (inh) Avoid combination
Metoprolol Epinephrine Additive Monitor pressor effects of epinephrine
Blood formation, coagulation, …… Acetylsalicylic acid Warfarin Additive Monitor bleeding
Ferrous sulfate Ofloxacin Absorption Separate doses by 4 or more hours
Levothyroxine Absorption Separate doses by 2 or more hours
Gastrointestinal drugs Pantoprazole Itraconazole Absorption Administer itraconazole with an acidic beverage, monitor response
Ranitidine Itraconazole Absorption Administer itraconazole with an acidic beverage, monitor response
Hormones and synthetic substitutes Dexamethasone Clarithromycin Metabolism (ind/inh)b Consider alternative antimicrobial therapy/monitor for dexamethasone toxic effects
Itraconazole Metabolism (ind) Avoid combination, monitor for therapeutic effects
Miscellaneous Cyclosporine Atorvastatin Metabolism (inh) Avoid combination
Mycophenolate Excretion Monitor mycophenolate dosing and response to therapy
  1. inh Inhibition, ind induction
  2. aThe precipitant drug causes the interaction and the object drug is affected by the interaction
  3. bBoth medications act on each other