Carbamazepine plasma concentrations

Carbamazepine is an anti-epileptic, which may also be used in the treatment of trigeminal neuralgia. Monitoring of carbamazepine plasma concentrations is required if high doses are administered as carbamazepine tends to be an autoinducer, meaning that the half-life is shortened following repeated administration of the drug. 

Conversely, carbamazepine concentrations can increase when risperidone is added when risperidone 1 mg/day was added in eight patients taking carbamaze-pine (mean dose 625 mg/day) carbamazepine plasma concentrations increased from 6.7 pg/ml at baseline to 8.0 pg/ ml 2 weeks later (243). 

CARBAMAZEPINE ANTIFUNGALS - ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE 1 plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t carbamazepine plasma concentrations These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Carbamazepine is a powerful inducer of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2), and the result is very low or undetectable plasma levels. 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 use of the less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessary to monitor carbamazepine levels... 

Oxcarbazepine is a weaker enzyme inducer than carbamazepine. When it is substituted for carbamazepine, plasma concentrations of concomitant drugs, such as valproate and neuroleptic drugs, can rise, owing to deinduction, leading to potential toxicity (17,18). 

Grimsley SR, Jann MW, Carter JG, D Mello AP, D Souza MJ. Increased carbamazepine plasma concentrations after fluoxetine coadministration. Clin Pharmacol Ther( 991) 50,10-15. 

Carbamazepine Increased plasma concentrations of carbamazepine symptoms of carbamazepine toxicity... 

Dextropropoxyphene Carbarn azepine Increased plasma-concentration of carbamazepine... 

Tegretol consists of carbamazepine, which is an anti-epileptic drug. There is a clinically significant drug interaction between carbamazepine and clarithromycin (macrolide antibacterial agent) resulting in higher plasma concentrations of carbamazepine. 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

Carbamazepine is slowly absorbed from the GI tract, and peak plasma concentrations are achieved in 2-8... 

Carbamazepine is widely distributed in the cerebros-piral fluid (CSF), bile, and saliva (AHFS, 2000). Plasma concentrations for anticonvulsant effect are in the range of 4-14 pg/mL. Carbamazepine, like DVP, is highly bound to protein (over 90%). At plasma concentrations of 1-50 pg/mL, 75%-90% of the drug is bound to plasma proteins (Trimble and Thompson, 1984). When protein-binding capacity is altered, marked changes in the free fractions can happen. Carbamazepine rapidly crosses the placenta, accumulates in fetal tissues, and is distributed in breast milk (AHFS, 2000). 

Carbamazepine, phenytoin, rifampicin. Plasma concentration of theophylline... 

Ethosuximide Carbamazepine Reduced plasma concentration of ethosuximide. 

The anticonvulsant therapeutic range for plasma concentrations of carbamazepine is 4 to 12 pg/mL. Hematological assessment in patients on carbamazepine therapy is appropriate because aplastic anemia and agranulocytosis have been reported in association with its use. 

Inducers of CYP3A4 such as St. John s wort preparations (H. perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile ... 

Cardiac depressant effects may occur when verapamil or diltiazem is combined with a (p-adrenoceptor antagonoist or a cardiac glycoside. Nifedipine and verapamil are metabolised by cytochrome P-450 3A4. Inhibitors of this enzyme, e.g. HIV-protease inhibitors, cimetidine, fluoxetine, ketoconazole, erythromycin, will increase plasma levels and the dose should be carefully monitored. Conversely, enzyme inducers, e.g. carbamazepine, rifampicin, phenytoin, will decrease their plasma concentrations. 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

Another important thing to remember about a CYP450 inducer is what happens if the inducer is stopped. Thus, if one stops smoking, 1A2 substrate levels will rise. If one stops carbamazepine, the plasma concentrations will rise for any concomitantly administered drug that is a 3A4 substrate. 

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Carbamazepine + phenytoin, tricyclic antidepressants, typical neuroleptics, valproate, clonazepam, warfarin, nefazodone and propoxyphene —> reduced plasma concentration of carbamazepine due to increased metabolism. 

Incompatibilities of metoclopramide depend on drug concentration, pH, and temperature. It is incompatible with cephalosporins, chloramphenicol, sodium bicarbonate, doxorubicin, cisplatin, and cyclophosphamide. Caution should be exercised with simultaneous administration of metoclopramide with lithium, sym-pathomimetics, antidepressants, bromocriptine, and carbamazepine. Omperazole interacts with tolbutamide, clarithromycin, and phenytoin. Coadministration of rantidine and cisapride increases the plasma concentration of rantidine. Abuse of senna laxative has been reported and may cause hepatitis.176-178... 

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