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Cordarone and Taxotere

Determining the interaction of Cordarone and Taxotere and the possibility of their joint administration.

Check result:
Cordarone <> Taxotere
Relevance: 20.12.2022 Reviewer: Shkutko P.M., M.D., in

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:

Amiodarone may significantly increase the blood levels of DOCEtaxel. This may increase the risk of side effects such as nausea, vomiting, diarrhea, mouth sores, fluid retention, nerve pain, numbness, tingling, muscle pain or weakness, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. 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 to safely use both medications. You should contact your doctor if you develop paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. 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.

Professional:

GENERALLY AVOID: Coadministration with amiodarone or dronedarone may significantly increase the plasma concentrations of docetaxel. The proposed mechanism is inhibition of the CYP450 3A4 and P-glycoprotein (P-gp)-mediated elimination of docetaxel by amiodarone and dronedarone. The interaction was described in a case report involving a 77-year-old woman with HER2-positive invasive ductal breast cancer on long-term amiodarone therapy who developed increasing abdominal discomfort and skin lesions during 4 cycles of paclitaxel (80 mg/m2 weekly) and trastuzumab. A subsequent switch to 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. In another case report, a 79-year-old man was hospitalized with fever, diarrhea, and grade 4 stomatitis and neutropenia after receiving a third cycle of docetaxel (35 mg/m2 on days 1 and 8 every 21 days) for metastatic androgen-independent prostate cancer while on dronedarone therapy (400 mg twice daily), which had been commenced 24 days earlier due to recurrence of atrial fibrillation. Docetaxel was still detectable in a plasma sample taken 24 days after it was last administered, at a concentration of approximately 2.4 ng/mL, even though its terminal half-life is about 12 hours. Unfortunately, the patient died after deterioration of his condition and multiple infectious complications.

MANAGEMENT: The use of docetaxel in combination with amiodarone or dronedarone should generally be avoided. If concomitant use is required, reduced dosage of docetaxel should be considered. Patients should also be closely monitored for the development of docetaxel toxicity such as myelosuppression, stomatitis, neurotoxicity (e.g., paraesthesia, dysesthesia, pain), myalgia asthenia, fluid retention, nausea, vomiting, and diarrhea.

References
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
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  • McInnes GT, Brodie MJ "Drug interactions that matter: a critical reappraisal." Drugs 36 (1988): 83-110
  • "Product Information. Taxotere (docetaxel)." Rhone-Poulenc Rorer, Collegeville, PA.
  • Vodovar D, Arnaout M, Mongardon N, et al. "Severe docetaxel overdose induced by pharmacokinetic interaction with dronedarone." J Clin Oncol 29 (2011): e694-5
  • Cerner Multum, Inc. "Australian Product Information." O 0
  • Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther 5 (2006): 833-9
  • Yong WP, Wang LZ, Tham LS, et al. "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol 62 (2008): 243-51
  • Aronson JK, Grahame-Smith DG "Clinical pharmacology: adverse drug interactions." Br Med J 282 (1981): 288-91
Cordarone

Generic Name: amiodarone

Brand name: Cordarone, Pacerone, Nexterone

Synonyms: n.a.

Taxotere

Generic Name: docetaxel

Brand name: Taxotere, Docefrez

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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