Particularly true if substrate drug depends on only one CYP450 enzyme for metabolismīecause they are known to cause clinically significant CYP450 drug interactions, always use caution when adding the following substances to medications that patients are taking: amiodarone (Cordarone), antiepileptic drugs, antidepressants, antitubercular drugs, grapefruit juice, macrolide and ketolide antibiotics, nondihydropine calcium channel blockers, or protease inhibitors.Īre either potent inhibitors or inducers of CYP450 enzymesĪmiodarone (Cordarone), cimetidine (Tagamet), ciprofloxacin (Cipro), fluvoxamine (Luvox ‡)Ĭarbamazepine (Tegretol), phenobarbital, rifampin (Rifadin), tobaccoĬaffeine, clozapine (Clozaril), theophyllineĪmiodarone, fluconazole (Diflucan), fluoxetine (Prozac), metronidazole (Flagyl), ritonavir (Norvir), trimethoprim/sulfamethoxazole (Bactrim, Septra)Ĭarbamazepine, phenobarbital, phenytoin (Dilantin), rifampinĬarvedilol (Coreg), celecoxib (Celebrex), glipizide (Glucotrol), ibuprofen (Motrin), irbesartan (Avapro), losartan (Cozaar) Severe toxicity can result if CYP450 enzyme–inhibiting drugs are added to the following medications: atypical antipsychotics, benzodiazepines, cyclosporine (Sandimmune), statins, or warfarin (Coumadin). Well-recognized cause of clinically significant drug interactions Patients should be monitored closely for the development of adverse drug effects or therapeutic failures when a potent CYP450 enzyme inhibitor or inducer is added to drugs metabolized by one or more CYP450 enzymes. Studies demonstrate a link between adverse effects and variant CYP450 alleles Genetic variations in CYP450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal doses. Large, prospective trials needed to demonstrate that genotype testing improves outcomes and is cost-effective Genotype testing may predict persons who are poor metabolizers or are nonresponsive to drugs metabolized by CYP450 enzymes. Although genotype tests can determine if a patient has a specific enzyme polymorphism, it has not been determined if routine use of these tests will improve outcomes. Knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inhibiting and inducing drugs, can help minimize the possibility of adverse drug reactions and interactions. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Genetic variability (polymorphism) in these enzymes may influence a patient's response to commonly prescribed drug classes, including beta blockers and antidepressants. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. Cytochrome P450 enzymes are essential for the metabolism of many medications.
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