Irinotecan drug interactions

As an inhibitor of CYP3A4 and CYP2C9, the potential for drug-drug interactions with atazanavir is great (Tables 49-3 and 49-4). Atazanavir AUC is reduced by 76% when combined with omeprazole thus, the combination is to be avoided. In addition, co-administration of atazanavir with other drugs that inhibit UGT1A1, such as indinavir and irinotecan, is contraindicated because of enhanced toxicity. Tenofovir and efavirenz should not be -administered with atazanavir unless ritonavir is added to boost levels. 

The possible impact of co-administered chemotherapies and radiation therapy on the PK of cetuximab was furthermore assessed using the population PK approach, as described in Section 14.6. The co-administered chemotherapies included cisplatin, carboplatin, paclitaxel, doxorubicin, irinotecan, and gemcitabine. The results of the analysis indicate that neither the co-administered chemotherapies nor radiation therapy had a significant impact on the PK of cetuximab. This finding suggests that the potential for PK-based drug-drug interactions with cetuximab is low. 

Further drug interactions occur if constitutive SN-38 glucuronidation capacity is modified. For example, phe-nobarbital may induce UGT lA activity, whereas valproic acid may inhibit it. Thus, co-administration can alter the clearance of irinotecan. 

Because both topotecan and irinotecan are metabolized by CYP3A4, the potential for drug-drug interactions must be evaluated. Reduced clearance was noted when azole antifungal agents and cyclosporine were coadministered with irinotecan, and accelerated clearance... 

Charasson V, Haaz M-C, Robert J. Determination of drug interactions occurring with the metabolic pathways of irinotecan. DrugMetab Dispos (2002) 30, 731-3. 

C. A., Sugiyama, Y., The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites, Drug Metab. Pharmacokinet. 2002, 17, 23-33. 

Hanioka N, Ozawa S, Jinno H, et al. Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-lO-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes. Drug Metab Dispos 2002 30(4) 391-6. 

The UK manufacturer of aprepitant recommends caution when it is used with antineoplastics that are metabolised by CYP3A4, particularly irinotecan, because of the possibility of increased toxicity with this drug. They also mention that etoposide, vinoreibine, docetaxel, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, were given without dosage adjustment for potential interactions, but as this was not a formal interaction study they recommend caution. However, with intravenous docetaxel, it appears that no important changes in pharmacokinetics occur, and therefore dosage adjustments are unlikely to be needed for this drug,... 

Cetuximab is used with irinotecan in the treatment of metastatie eoloreetal eaneer. In a study 14 patients with advanced EGFR (epidermal growth fae-tor responsive) positive adenocarcinoma were given either irinoteean 350 mg/m every 3 weeks and cetuximab 400 mg/m at week 2 then 250 mg/m eaeh week or cetuximab each week starting at week 1 and irinotecan starting at week 4. There was at least a 1 hour period between the end of the cetuximab infusion and the start of the irinotecan infusion. No evidence was found of a pharmacokinetic interaction between eetuximab and irinotecan, nor was there any significant increase in serious toxieities for the combination, when compared with treatment with either drug alone. ... 

Mross K, Steinbild S, Baas F, Reil H Buss P, Mersmann S, Voliotis D, Schwartz B, Brendel E. Drug-dnig interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients widi solid tumors. Int J ClinPharmacol 77i r(2003) 41,618-19. 

Hajan R, Guan HT (2013) Speetrophotometric studies on the thermodynamics of the ds-DNA interaction with irinotecan for a better understanding of anticancer drug-DNA interactions. J Spectrosc. ID 380352. http //dx.doi.org/10.1155/2013/380352... 

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