Paclitaxel Concentrate Injection and Zykadia

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.

Consumer information for this interaction is not currently available.MONITOR: Coadministration with inhibitors of CYP450 2C8 and/or 3A4 may increase the plasma concentrations of paclitaxel, which has been found in vitro to be a substrate of these isoenzymes. Formal clinical drug interaction studies have not been conducted. However, in a case report involving a 77-year-old woman with HER2-positive invasive ductal breast cancer on long-term amiodarone therapy, 4 cycles of paclitaxel (80 mg/m2 weekly) and trastuzumab led to development of increasing abdominal discomfort and skin lesions and a diagnosis of paclitaxel-induced skin toxicity. Switching to reduced dose docetaxel (100 mg or 75 mg/m2 weekly) led to the development of severe skin and mucosal toxicity, requiring hospitalization 8 days after the first docetaxel dose was administered. Analysis of two blood samples taken 9 and 10 days after docetaxel administration showed an approximately fivefold increase in its AUC as well as the presence of paclitaxel in unquantifiable levels, 20 and 21 days after it was last administered. The authors of this case study propose that, in addition to CYP450 3A4 inhibition, CYP450 2C8 and P-glycoprotein inhibition due to amiodarone may also contribute to the interaction. MANAGEMENT: Clinicians should consider the potential for interaction with drugs that inhibit CYP450 2C8 and/or 3A4 and monitor for evidence of dose-related toxicities of paclitaxel during coadministration, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy. References Starr SP, Hammann F, Gotta V, et al. "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol 450 (2016): 22-27 Cerner Multum, Inc. "Australian Product Information." O 0 Bergmann TK, Filppula AM, Launiainen T, Nielsen F, Backman J, Brosen K "Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma." Br J Clin Pharmacol (2015): Spencer CM, Faulds D "Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer." Drugs 48 (1994): 794-847 "Product Information. Taxol (paclitaxel)." Bristol-Myers Squibb, Princeton, NJ. "Product Information. Abraxane (paclitaxel protein-bound)." American Pharmaceutical Partners, Schaumberg, IL. Bun SS, Ciccolini J, Bun H, Aubert C, Catalin J "Drug interactions of paclitaxel metabolism in human liver microsomes." J Chemother 15 (2003): 266-74 Jamis-Dow CA, Klecker RW, Katki AG, Collins JM "Metabolism of Taxol by human liver microsomes and effect of inhibitors (Meeting abstract)." Proc Annu Meet Am Assoc Cancer Res 34 (1993): a21981993 View all 8 references

MONITOR: Coadministration with inhibitors of CYP450 2C8 and/or 3A4 may increase the plasma concentrations of paclitaxel, which has been found in vitro to be a substrate of these isoenzymes. Formal clinical drug interaction studies have not been conducted. However, in a case report involving a 77-year-old woman with HER2-positive invasive ductal breast cancer on long-term amiodarone therapy, 4 cycles of paclitaxel (80 mg/m2 weekly) and trastuzumab led to development of increasing abdominal discomfort and skin lesions and a diagnosis of paclitaxel-induced skin toxicity. Switching to reduced dose docetaxel (100 mg or 75 mg/m2 weekly) led to the development of severe skin and mucosal toxicity, requiring hospitalization 8 days after the first docetaxel dose was administered. Analysis of two blood samples taken 9 and 10 days after docetaxel administration showed an approximately fivefold increase in its AUC as well as the presence of paclitaxel in unquantifiable levels, 20 and 21 days after it was last administered. The authors of this case study propose that, in addition to CYP450 3A4 inhibition, CYP450 2C8 and P-glycoprotein inhibition due to amiodarone may also contribute to the interaction.

MANAGEMENT: Clinicians should consider the potential for interaction with drugs that inhibit CYP450 2C8 and/or 3A4 and monitor for evidence of dose-related toxicities of paclitaxel during coadministration, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy.

Paclitaxel Concentrate Injection

Generic Name: paclitaxel

Brand name: Onxol, Taxol

Synonyms: Paclitaxel, PACLitaxel (Conventional)

What is Paclitaxel Concentrate Injection?

Zykadia

Generic Name: ceritinib

Brand name: Zykadia

Synonyms: n.a.

What is Zykadia?