Font size

Home	About Taxotere®	Dosage Administration	Professional Resources	Consumer
	Important Safety Info. Clinical Pharmacology Adverse Events	Premedication Dosing Guidelines Preparation Administration Handling	Useful Patient Web Sites Patient Education Nurses' Resources Reimbursement

> Home > About Taxotere® > Clinical Pharmacology

Important Safety Information

Clinical Pharmacology

Mechanism Of Action

Pharmacokinetics Profile

Drug Interactions

Adverse Events

Metastatic Breast Cancer

Early-Stage Breast Cancer

Advanced NSCLC

Metastatic Androgen Independent Prostate Cancer

IMPORTANT SAFETY INFORMATION including BOXED WARNING

WARNING
The incidence of treatment-related mortality associated with Taxotere® therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Taxotere® as a single agent at a dose of 100 mg/m2 (see WARNINGS section of the prescribing information)

Continued below

Taxotere^® (docetaxel) Injection Concentrate: Clinical pharmacology

Unique chemical structure^1-3

Taxotere^® has a hydroxyl group. This extra hydroxyl group (1 in figure below) leads to greater water solubility, obviating the need to use Cremophor^® as a solvent
Taxotere^® has C-13 side-chain variations and a unique ester side chain (2 in figure below)

The chemical structure of Taxotere^®⁴

Cremophor^® free⁴

Taxotere^®, which is formulated with polysorbate 80, is Cremophor^® free
- Taxotere^®¹ must not be given to patients who have a history of severe hypersensitivity reactions to Taxotere^® or to other drugs formulated with polysorbate 80
- All patients receiving Taxotere^® should be premedicated with oral corticosteroids such as dexamethasone 16 mg/day (eg., 8 mg BID) in order to reduce the incidence and severity of fluid retention, as well as the severity of hypersensitivity reactions

Protein bound^4,5

Animal studies have demonstrated that albumin accumulates in tumors, thus boosting albumin-bound drug delivery and uptake into tumor cells
In vitro studies showed that Taxotere^® is about ≈94% protein bound
- Albumin is a principal protein involved

Linear pharmacokinetics²

Taxotere^® has a linear pharmacokinetic profile

The following pages provide detailed information on the clinical pharmacology of Taxotere^®:

IMPORTANT SAFETY INFORMATION

WARNINGS:

The incidence of treatment-related mortality associated with Taxotere® therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Taxotere® as a single agent at a dose of 100 mg/m²
Taxotere® should not be given to patients with bilirubin >upper limit of normal (ULN), or to patients with AST and/or ALT>1.5 X ULN concomitant with alkaline phosphatase >2.5 X ULN
- Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death
- Patients with isolated elevations of transaminase >1.5 X ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death
- Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of Taxotere® therapy
Taxotere® therapy should not be given to patients with neutrophil counts of <1500 cells/mm³
- In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood cell counts should be performed on all patients receiving Taxotere®
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received the recommended 3-day dexamethasone premedication
- Hypersensitivity reactions require immediate discontinuation of Taxotere® infusion and administration of appropriate therapy
Taxotere® must not be given to patients who have a history of severe hypersensitivity reactions to Taxotere® or to other drugs formulated with polysorbate 80
Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone premedication regimen. It was characterized by one or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites)

Neutropenia (<2,000 neutrophils/mm³) occurs in virtually all patients given 60-100 mg/m² of Taxotere® and grade 4 neutropenia (<500 cells/mm³) occurs in 85% of patients given 100 mg/m² and 75% of patients given
60 mg/m²
Patients should be premedicated with oral corticosteroids prior to each Taxotere® administration to reduce the incidence and severity of fluid retention. Patients with pre-existing effusions should be closely monitored from the first dose for possible exacerbation of the effusions
Treatment-related acute myeloid leukemia (AML) or myelodysplasia has occurred in patients given anthracyclines and/or cyclophosphamide, including use with Taxotere® in adjuvant therapy of breast cancer
Localized erythema of the extremities with edema followed by desquamation has been observed
- In case of severe skin toxicity, an adjustment in dosage is recommended
Severe neurosensory symptoms (paresthesia, dysesthesia, pain) were observed in 5.5% (53/965) of metastatic breast cancer patients, and resulted in treatment discontinuation in 6.1%
- When these symptoms occur, dosage must be adjusted; if symptoms persist, treatment should be discontinued
Severe asthenia was reported in 14.9% (144/965) of metastatic breast cancer patients, but led to treatment discontinuation in only 1.8%
- Symptoms of fatigue and weakness may last a few days up to several weeks and may be associated with deterioration of performance status in patients with progressive disease
Taxotere® can cause fetal harm when administered to pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Taxotere®
The most common adverse reactions across all Taxotere® indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions and myalgia
In patients treated with TCF for gastric cancer, the incidence of serious adverse events was higher in patients ≥65 years than in younger patients. Adverse events (all grades) occurring at rates ≥10% higher in elderly patients included lethargy, stomatitis, diarrhea, dizziness, edema, and febrile neutropenia/neutropenic infection.
Taxotere® should be administered in a facility equipped to manage possible complications (e.g. anaphylaxis)

Please click here for Taxotere full prescribing information, including boxed WARNING.

Taxotere® (docetaxel) Injection Concentrate Indications

Breast Cancer
TAXOTERE® is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy
TAXOTERE® in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer

Advanced Non-Small Cell Lung Cancer
TAXOTERE®, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy
TAXOTERE® in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic NSCLC who have not previously received chemotherapy for this condition.

Metastatic Androgen-Independent Prostate Cancer
TAXOTERE® in combination with prednisone is indicated for the treatment of patients with androgen-independent (hormone-refractory) metastatic prostate cancer.

Advanced Gastric/GE Junction Cancer
TAXOTERE® in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.

Locally Advanced Head and Neck Cancer
TAXOTERE® in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

Cremophor is a registered trade mark of BASF Aktiengensellschoft.

References

Ringel I, Horwitz SB. Studies with RP 56976 (Taxotere^®): a semisynthetic afalogue of Taxol. J Natl Cancer Inst. 1991;83:288-291.
Eisenhauer EA, Vermorken JB. The taxoids: comparative clinical pharmacology and therapeutic potential. Drugs. 1998;55:5-30.
Bissery M-C, Nohynek G, Sanderink G-J, Lavelle F. Docetaxel (Taxotere^®): a review of preclinical and clinical experience. Part 1: preclinical experience. Anticancer Drugs. 1995;6:339-355.
Taxotere^® Prescribing Information. Bridgewater, NJ: sanofi-aventis U.S. LLC; May 2010.
Wunder A, Müller-Ladner U, Stelzer EHK, et al. Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol. 2003;170(9):4793-4801.

Taxotere® (docetaxel) Injection Concentrate: Clinical pharmacology

Unique chemical structure1-3

The chemical structure of Taxotere®4

Cremophor® free4

Protein bound4,5