No formal drug-drug interaction studies have been performed.
Intravenous Pertuzumab: A sub-study in 37 patients in the pivotal trial CLEOPATRA showed no evidence of drug-drug interaction between pertuzumab and trastuzumab and between pertuzumab and docetaxel. In addition, no clinically relevant pharmacokinetic interaction of co-administered docetaxel or trastuzumab on pertuzumab was evident, based on the population pharmacokinetics analysis. This lack of drug-drug interaction was confirmed by pharmacokinetic data from the NEOSPHERE and APHINITY studies.
Five studies evaluated the effects of pertuzumab on the pharmacokinetics of coadministered cytotoxic agents, docetaxel, paclitaxel, gemcitabine, capecitabine, carboplatin, and erlotinib. There was no evidence of any pharmacokinetics interaction between pertuzumab and any of these agents. The pharmacokinetics of pertuzumab in these studies was comparable to those observed in single-agent studies.
Intravenous trastuzumab: There have been no formal drug interaction studies performed with trastuzumab in humans. Clinically significant interactions between trastuzumab and the concomitant medications used in clinical trials have not been observed.
In studies where trastuzumab was administered in combination with docetaxel, carboplatin, or anastrozole, the pharmacokinetics of these medications was not altered nor was the pharmacokinetics of trastuzumab altered.
Concentrations of paclitaxel and doxorubicin (and their major metabolites 6-α hydroxyl-paclitaxel, POH, and doxorubicinol, DOL) were not altered in the presence of trastuzumab. However, trastuzumab may elevate the overall exposure of one doxorubicin metabolite, (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite is unclear. No changes were observed in trastuzumab concentrations in the presence of paclitaxel and doxorubicin.
The results of a drug interaction substudy evaluating the pharmacokinetics of capecitabine and cisplatin when used with or without trastuzumab suggested that the exposure to the bioactive metabolites (e.g. 5-FU) of capecitabine was not affected by concurrent use of cisplatin or by concurrent use of cisplatin plus trastuzumab. However, capecitabine itself showed higher concentrations and a longer half-life when combined with trastuzumab. The data also suggested that the pharmacokinetics of cisplatin were not affected by concurrent use of capecitabine or by concurrent use of capecitabine plus trastuzumab.