Irinotecan and Tegretol

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

CarBAMazepine may significantly reduce the blood levels of irinotecan, which may make the medication less effective in treating your cancer. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of irinotecan and its pharmacologically active metabolite, SN-38. Irinotecan is partially metabolized by CYP450 3A4 to inactive substances, and induction of this process results in less of the drug available for conversion to SN-38 via hepatic carboxylesterases. Available data also suggest induction of other enzymatic pathways (e.g., UGT1A1; carboxylesterases) and drug transporters (e.g., multispecific organic anion transporter, or MRP2; mitoxantrone-resistance half transporter protein, or MXR) that may be involved in the clearance of irinotecan and/or SN-38, although the extent to which they contribute to the interaction is unknown. In a study of patients with malignant glioma, irinotecan clearance was 61% greater in the group receiving enzyme-inducing anticonvulsants (n=34) than in the group receiving other anticonvulsants (n=22). In a study of pediatric high-grade glioma patients, a 1.5-fold increase in the median clearance of irinotecan and a 20-fold decrease in the median systemic exposure to SN-38 were observed in patients receiving enzyme-inducing anticonvulsants compared to those not receiving the anticonvulsants. Patients receiving enzyme-inducing anticonvulsants in these studies also experienced milder toxicities or tolerated higher dosages of irinotecan. In a phase II clinical trial, patients receiving irinotecan for malignant glioma had an unusually low incidence of toxicity, and AUCs of irinotecan and SN-38 were 40% and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer. A pharmacokinetic interaction was suspected, as more than 90% of the glioma patients received concomitant enzyme-inducing anticonvulsants and/or dexamethasone, while the colorectal cancer patients did not. In a pediatric case study, irinotecan pharmacokinetics were determined in a 15-year-old boy on day 1 of two treatment cycles (50 mg/m2 daily for 5 days every 21 days)--one before and one after the addition of phenytoin. Irinotecan clearance increased by 168% and the AUC of irinotecan and SN-38 decreased by 63% and 60%, respectively, in the presence of phenytoin. Similarly, in a 14-year-old girl receiving irinotecan daily for 5 days on two consecutive weeks every 21 days for two cycles, pharmacokinetic studies on day 8 of each cycle showed that irinotecan clearance decreased by 42% and the AUC of irinotecan and SN-38 increased by 76% and 138%, respectively, following discontinuation of phenytoin just prior to cycle 2.

MANAGEMENT: Concomitant use of irinotecan with potent CYP450 3A4 inducers should generally be avoided. Consideration should be given to substituting nonenzyme-inducing agents at least one to two weeks prior to initiation of irinotecan therapy whenever possible.

Irinotecan

Generic Name: irinotecan

Brand name: Camptosar

Synonyms: Irinotecan (Conventional)

What is Irinotecan?

Tegretol

Generic Name: carbamazepine

Brand name: Carbatrol, Epitol, Equetro, Tegretol, Tegretol XR, Tegretol, Tegretol XR

Synonyms: n.a.

What is Tegretol?