Phenytoin CYPs induced

IRINOTECAN 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS -St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentrations of irinotecan and risk of 1 therapeutic efficacy. The effects may last for 3 weeks after discontinuation of CYP-inducer therapy Due to induction of CYP3A4-mediated metabolism of irinotecan Avoid concomitant use when ever possible if not, t dose of irinotecan by 50%... 

TeUthromycin is both a substrate and a strong inhibitor of CYP3A4. Coadministration of rifampin, a potent CYP inducer, decreases the serum concentrations of teUthromydn by 80%, whUe CYP3A4 inhibitors (e.g., itraconazole) increase peak serum concentrations. Serum concentrations of CYP3A4 substrates (e.g., pimozide, cisapride, midazolam, statins, cyclosporine, phenytoin) are increased by telithromycin. TeUthromycin also increases peak serum concentrations of metoprolol and digoxin. 

In other instances, a nontoxic parent compound is transformed by CYP into a reactive metabolite that is toxic to the mitochondria. This is seen with acetaminophen, which is transformed by CYP2E1 to the chemically reactive, N-acetyl-p-benzoquinone imine. The hepatic toxicity of acetaminophen is increased in alcoholics (Seef et al. 1986). Ethanol abuse increases CYP2E1 in the endoplasmic reticulum and in the mitochondria (Robin et al. 2005). The mitochondrial localization of CYP2E1 may lead to the in situ generation of reactive metabolites of acetaminophen in the mitochondria, where the metabolite may trigger MPT (Weis et al. 1992 Masubuchi et al. 2005). Mitochondria also contain other inducible CYPs, such as CYPlAl and CYP2B1 (Anandatheerthavarada et al. 1997 Sepuri et al. 2007). The concomitant administration of CYP-inducers, phenobarbital or phenytoin increases the hepatotoxicity of valproic acid, which is transformed by microsomal and mitochondrial CYPs and then p-oxidation enzymes into a reactive... 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

CYP 450 Drugs that induce liver enzymes (eg, phenytoin, carbamazepine, phenobarbital) increase the metabolism and clearance of zonisamide and decrease its half-life. Concurrent medication with drugs that induce or inhibit CYP3A4 would be expected to alter serum concentrations of zonisamide. Zonisamide is not expected to interfere with the metabolism of other drugs that are metabolized by cytochrome P450 isozymes. 

Clozapine is metabolized by hepatic CYP 1A2 and, to a lesser degree, CYP 3A3/4 therefore, the drug is subject to changes in serum concentration when combined with medications that inhibit or induce these enzymes. Serum clozapine levels increase with coadministration of fluvoxamine or erythromycin and decrease with coadministration of phenobarbital or phenytoin and with cigarette smoking (Byerly and DeVane 1996). These pharmacokinetic interactions are particularly important because of the dose-dependent risk of seizures. 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE CARBAMAZEPINE, PHENYTOIN L plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t phenytoin levels, but clinical significance uncertain. Carbamazepine plasma concentrations are also t These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Phenytoin and carbamazepine are powerful inducers of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2) the result is veiy low or undetectable plasma levels. Phenytoin extensively 1AUC of itraconazole by more than 90%. Inhibition of P-gp T bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessaiy to monitor phenytoin and carbamazepine levels... 

Phenobarbital is metabolized by CyP 2C19 to p-hydroxy-phenobarbital, which is largely excreted as the glucuronide (by UGT). When renal and hepatic function are decreased, patients experience decreased clearance of the drug. Alcohol, carbamazepine, other barbiturates, and rifampin induce oxidative enzymes (CyP 2C19 and 2C9) this induction results in increased metabolism of phenytoin, reduced serum concentration of phenobarbital, and a reduced pharmaco-... 

Tiagabine has an elimination half-Ufe of 7 to 9 hours. In patients receiving CyP 3A4 inducing anti-epileptic drugs (AEDs), the elimination half-life decreases to 4 to 7 hours. Phenytoin, phenobarbital, and carbamazepine are CyP 3A4 inducers. Valproic acid and gabapentin are not. Tiagabine is not considered to be a CyP 3A4 inducer. ... 

Although a less potent inducer of CYPs than rifampin, rifabutin does induce hepatic microsomal enzymes, with its administration decreasing the half-life of a number of different compounds, including zidovudine, prednisone, digi-toxin, quinidine, ketoconazole, propranolol, phenytoin, sulfonylureas, and warfarin. It has less effect than does rifampin on serum levels of indinavir and nelfinavir. 

Because benzodiazepines do not significantly induce the synthesis of hepatic CYPs, chronic benzodiazepine administration usually does not result in the accelerated metabolism of benzodiazepines or other substances. Cimetidine and oral contraceptives inhibit N-dealkylation and 3-hydroxylation of benzodiazepines, as do ethanol, isoniazid, and phenytoin to a lesser degree. These reactions usually are reduced to a greater extent in elderly patients and in patients with chronic liver disease than are those involving conjugation. 

Concurrent administration of any drug metabolized by CYP2C9 or CYP2C10 can increase the plasma concentration of phenytoin by decreasing its rate of metabolism. Conversely, drugs that induce hepatic CYPs can increase phenytoin catabolism. Thus, carbamazepine causes a decrease in phenytoin concentration and phenytoin reduces the concentration of carbamazepine. Interaction between phenytoin and phenobarbital is variable. 

Doxycycline at recommended doses does not accumulate significantly in patients with renal failure and thus is one of the safest of the tetracyclines in this setting. The drug is excreted in the feces. Its tj 2 may be significantly shortened by concurrent therapy with barbiturates, phenytoin, rifampin, or other inducers of hepatic CYPs. 

DRUG INTERACTIONS Chloramphenicol inhibits hepatic CYPs and thereby prolongs the half-hves of CYP substrates, including coumadin, phenytoin, chlorpropamide, HIV protease inhibitors, rifabutin, and tolbutamide. Severe toxicity and death have occurred due to these drug interactions. Concurrent administration ofphenobarbital or rifampin, which potently induce CYPs, shortens chloramphenicors t j and may result in subtherapeutic drug concentrations. 

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