Taxotere

Aseptically withdraw the required amount of TAXOTERE premix solution (10 mg docetaxel/mL) with a calibrated syringe and inject the required volume of premix solution into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 to 0.74 mg/mL. If a dose greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.

TAXOTERE infusion solution should be aseptically administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.

Contact of the undiluted concentrate with plasticized PVC equipment or devices used to prepare solution for infusion is not recommended. In order to minimize patient exposure to plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, TAXOTERE infusion solution should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.

For prostate cancer, given the concurrent use of prednisone or prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the TAXOTERE infusion.

If the vials are stored under refrigeration, allow the required number of TAXOTERE concentrate and diluent vials to stand at room temperature for approximately 5 minutes.

After reconstitution, the TAXOTERE premix is stable for 8 hours at room temperature or between 2 and 8°C (see Storage and Stability).

Like many other chemotherapeutic agents, careful monitoring of neutrophil counts are an essential part of TAXOTERE therapy. TAXOTERE should not be administered until the neutrophil count is at least 1500 cells/mm³. Patients who experience either febrile neutropenia, severe neutropenia (neutrophil <500 cells/mm³ for more than one week), severe or cumulative cutaneous reaction, or severe neurosensory signs and/or symptoms during TAXOTERE therapy should have the dosage of TAXOTERE reduced from 100 mg/m² to 75 mg/m². When TAXOTERE is given in combination, the dose of TAXOTERE should be reduced from 75 mg/m² to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued. Alternatively, prophylactic G-CSF may be used in patients with either prior febrile neutropenia or severe infection in order to maintain dose intensity (see Warnings and Precautions).

Patients who receive adjuvant therapy for breast cancer and who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their TAXOTERE dose reduced to 60 mg/m². If G-CSF is not used, the TAXOTERE dose should be reduced from 75 to 60 mg/m².

In order to reduce the incidence and severity of fluid retention, all patients should be pretreated with oral corticosteroids. The recommended premedication should consist only of oral corticosteroids, such as dexamethasone 16 mg per day (e.g. 8 mg BID), for 3 days starting one day prior to each TAXOTERE administration. Antihistamines have not been shown to be useful in controlling fluid retention.

The recommended dosage of TAXOTERE (docetaxel for injection) is 100 mg/m² administered as a one-hour infusion every 3 weeks. When used in combination, TAXOTERE is administered at the recommended dosage of 75 mg/m².

Based on the population pharmacokinetics, there are no special instructions for the use in the elderly (see Warnings and Precautions).

The recommended dosage of TAXOTERE is 75 mg/m² administered as a one-hour infusion every 3 weeks. Concomitant treatment with prednisone or prednisolone 5 mg orally twice daily is administered continuously.

Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities. See Dosing Adjustment. In addition to G-CSF, the prophylactic use of antibiotics may provide additional benefit.

TAXOTERE must be administered intravenously. It is extremely important that the intravenous needle or catheter be properly positioned before any TAXOTERE is injected. Leakage into surrounding tissue during intravenous administration of TAXOTERE may cause considerable irritation, local tissue necrosis and/or thrombophlebitis. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should be introduced into another vein.

Please refer to the Special Handling Instructions as well.

In order to reduce the incidence of febrile neutropenia and infections, the prophylactic use of antibiotics is recommended to patients treated for head and neck cancer. The treatment should consist of oral fluroquinolone antibiotics, or equivalent oral or intravenous antibiotics, for 10 days starting on day 5 of each cycle of TAXOTERE administration.

Based on pharmacokinetic data obtained with TAXOTERE at 100 mg/m² as single agent, patients who have both elevations of transaminase values (ALT and/or AST) greater than 1.5 times the upper limit of normal (ULN) range and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of TAXOTERE is 75 mg/m². For those patients with serum bilirubin greater than ULN and/or ALT and AST greater than 3.5 times ULN associated with alkaline phosphatase greater than 6 times ULN, TAXOTERE should not be used unless strictly indicated. There are no data available in patients with hepatic impairment treated with TAXOTERE combination (see Warnings and Precautions).

The TAXOTERE (docetaxel for injection) dose is 75 mg/m² administered 1-hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 courses (see also Dosing Adjustment).

TAXOTERE concentrated solution requires dilution prior to administration. Please follow the preparation instructions provided below.

Cases of renal insufficiency, including renal failure, have been reported in clinical trials with docetaxel, and they are typically associated with concomitant nephrotoxic drugs.

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with TAXOTERE. In some cases, multiple factors such as concomitant infections, concomitant medications and underlying disease may have contributed to the development of these effects.

In 251 patients who received TAXOTERE in combination with capecitabine, 68% had grade 3 or 4 neutropenia, 2.8% had grade 3 or 4 thrombocytopenia and 9.6% had grade 3 or 4 anemia.

hypersensitivity (1.20).

Rare cases of lacrimation with or without conjunctivitis have been reported and very rarely cases of lacrimal duct obstruction resulting in excessive tearing have been reported primarily in patients receiving other anti-tumor agents concomitantly. Rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring during drug infusion and in association with hypersensitivity reactions have been reported. These were reversible upon discontinuation of the infusion.

Acute respiratory distress syndrome, interstitial pneumonia, pulmonary fibrosis and radiation recall phenomena have rarely been reported. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.

Very rare cases of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been reported in association with TAXOTERE when used in combination with other chemotherapy agents and/or radiotherapy.

ataxia (0.39), syncope (1.20), taste loss (0.80), polyneuropathy (0.39), migraine (0.39).

In patients treated by docetaxel as single agent, at 100 mg/m², the median cumulative dose to treatment discontinuation was more than 1000 mg/m² and the median time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and severe retention is delayed (median cumulative dose: 818.9 mg/m²) in patients with premedication compared with patients without premedication (median cumulative dose: 489.7 mg/m²); however, it has been reported in some patients during early courses of therapy. Fluid retention has not been accompanied by oliguria or hypotension, and was slowly reversible after TAXOTERE treatment was stopped.

neutropenic sepsis (2.39), lower respiratory tract infection nos (0.39), pharyngitis (0.39), otitis media (0.39), sepsis (0.39), bronchopneumonia (0.39).

The following events were observed to be ongoing at the median follow-up time of 55 months: alopecia (22/687), amenorrhea (133/233), neurosensory (9/73) and peripheral edema (18/112).

Ear and labyrinth disorders include rare cases of ototoxicity, hearing disorders and/or hearing loss which have been reported, including cases associated with other ototoxic drugs.

rigors (0.39), injection site infection (0.39), neuralgia (0.39).

Rare cases of convulsion or transient loss of consciousness have been observed with TAXOTERE administration. These reactions sometimes appear during the infusion of the drug.

More cardiovascular events were reported in the TAC arm than in the FAC arm: treatment related dysrhythmias, all grades (3.9% vs 2.9%), treatment related hypotension, all grades (1.5% vs 0.5%) and clinically significant treatment-emergent congestive heart failure (CHF), cardiac function grade 3-4 (1.6% vs 0.5%). One TAC-treated patient died due to heart failure. While left ventricular ejection fraction (LVEF) was measured at baseline as a study requirement in the TAX316 study, repeat measurements were not performed unless considered clinically relevant by the investigator. Of the patients with repeat LVEF assessment, 14/66 (21%) in the TAC treatment group and 4/48 (8.3%) in the FAC treatment group were reported to have LVEF declines to levels below the lower limit of normal.

Treatment related fever in the absence of infection was seen in 43.1% (Gr 3/4: 1.2%) of TAC-treated patients and in 13.2% (Gr 3/4: 0.0%) of FAC-treated patients. Treatment related infection was seen in 27.2% (Gr 3/4: 3.2%) of TAC-treated patients and in 17.4% (Gr 3/4: 1.4%) of FAC-treated patients. There were no septic deaths in either treatment arm. G-CSF was used as treatment or secondary prophylaxis in 29.2% of TAC-treated patients compared to 5.6% of FAC-treated patients.

Rare occurrences of gastrointestinal perforation, dehydration as a consequence of gastrointestinal events, ischemic colitis, colitis and neutropenic enterocolitis have been reported.

Rare cases of ileus and intestinal obstruction have been reported.

Of the 332 patients treated with TAXOTERE every three weeks in the prostate cancer study (TAX 327), 208 patients were 65 years of age or greater and 67 patients were older than 75 years. In patients treated with TAXOTERE every three weeks, the incidence of anemia, infection, nail changes, anorexia, weight loss, regardless of relationship to TAXOTERE, occurred at rates ≥10% higher in patients who were 65 years of age or greater compared to younger patients. Fatigue, all grades, was one of the most commonly reported TEAEs (regardless of relationship to TAXOTERE in patients treated with TAXOTERE every three weeks, but grade 3-4 were experienced in only 1.6% of subjects <65 years old, 6.3% in those ≥65 years, and 10.4% in those ≥75 years old. Similarly diarrhea, all grades, was also commonly reported, but the incidence of grade 3-4 diarrhea was much lower for each age category, 1.6%, 2.4% and 3.0% respectively. There was a similar pattern for the incidence of infection grade 3-4, in the three age categories the incidence was 4.0%, 6.7%, and 9.0%, respectively.

Generalised and localised pain including chest pain without any cardiac or respiratory involvement.

jaundice (0.39), abnormal liver function tests (0.39), hepatic failure (0.39), hepatic coma (0.39), hepatotoxicity (0.39).

Disseminated intravascular coagulation (DIC), often in association with sepsis, or multiorgan failure, has been rarely reported.

Infusion site reactions occurred in 6% of the patients treated with TAXOTERE as a single agent for various tumor types and were generally mild. These reactions included skin sensitivities such as hyperpigmentation, inflammation, local erythema, redness or dryness of the skin, or swelling of the vein. Phlebitis or extravasation was observed less frequently.

Rare cases of severe hypersensitivity reactions/anaphylactic shock have been reported. Very rare cases of anaphylactic shock with a fatal outcome have been reported in patients who received premedication.

The percentage of events related to combination therapy might be different from those related to monotherapy with TAXOTERE. Please refer to Table 4, Table 5, Table 6, Table 7 for adverse drug reactions related to different combination therapies.

Dehydration and pulmonary oedema have been rarely reported.

In addition to gastrointestinal events reflected in Table 4, 4 patients in the TAC treatment arm and 1 patient in the FAC treatment arm were reported to have treatment related colitis/enteritis/large intestine perforation. Two of the 4 TAC-treated patients required treatment discontinuations; no deaths due to these events occurred.

Of the 744 patients treated with TAC in the TAX316 study, 33.1% experienced severe TEAEs possibly or probably related to treatment compared to 22.1% of the 736 patients treated with FAC. Dose reductions due to hematologic toxicity occurred in 1% of cycles in the TAC arm compared to 0.1% of cycles in the FAC arm. Six percent of patients treated with TAC discontinued treatment due to adverse events, compared to 1.1% treated with FAC; fever in the absence of infection and allergy being the most common reasons for withdrawal among TAC-treated patients. Two TAC-treated patients died within 30 days of their last study treatment; 1 death was considered to be related to study drug. Two FAC-treated patients died within 30 days of their last study treatment; 1 death was considered to be related to study drug.

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, have been reported.

Rare occurrences of venous thromboembolic events and myocardial infarction have been reported.

TAXOTERE is indicated as monotherapy in the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck after failure of a previous chemotherapy regimen.

TAXOTERE should be administered under the supervision of a physician experienced in the use of antineoplastic agents.

TAXOTERE (docetaxel for injection) in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.

The effectiveness of TAXOTERE in combination with doxorubicin and cyclophosphamide is based on improved disease free survival and overall survival in comparison to the combination of fluorouracil, doxorubicin and cyclophosphamide at a median follow up of 55 months. However long-term data are not yet available.

TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic breast cancer. TAXOTERE, in combination with doxorubicin as first line therapy, should be reserved for patients with potentially life threatening disease (such as visceral or lung metastatic disease).

TAXOTERE in combination with Xeloda (capecitabine) is indicated for the treatment of patients with advanced or metastatic breast cancer after failure of prior anthracycline containing chemotherapy.

TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer in monotherapy or in combination with platinum derivatives.

TAXOTERE in combination with prednisone or prednisolone is indicated for the treatment of patients with androgen-independent (hormone-refractory) metastatic prostate cancer.

TAXOTERE is indicated for the treatment of metastatic carcinoma of the ovary after failure of first-line or subsequent chemotherapy.

Each single-dose vial of sterile, non-pyrogenic, nonaqueous, clear yellow to brownish-yellow viscous solution contains: docetaxel (anhydrous) 20 mg in 0.5 mL polysorbate 80 (Fill: docetaxel 24.4 mg in 0.61 mL polysorbate 80) with an accompanying sterile, non-pyrogenic diluent vial containing 1.98 mL of ethanol 13% in water for injection. This overfill ensures that there is a minimal extractable premix volume of 2 mL containing 10 mg/mL docetaxel which corresponds to the labelled amount of 20 mg/vial. Nonmedicinal ingredients: ethyl alcohol, polysorbate 80 and water for injection. Both items are in blister packs in 1 carton.

Each single-dose vial of sterile, non-pyrogenic, nonaqueous, clear yellow to brownish-yellow viscous solution contains: docetaxel (anhydrous) 80 mg in 2 mL polysorbate 80 (Fill: docetaxel 94.4 mg in 2.36 mL polysorbate 80) with an accompanying sterile, non-pyrogenic diluent vial containing 7.33 mL of ethanol 13% in water for injection. This overfill ensures that there is a minimal extractable premix volume of 8 mL containing 10 mg/mL docetaxel which corresponds to the labelled amount of 80 mg/vial. Nonmedicinal ingredients: ethyl alcohol, polysorbate 80 and water for injection. Both items are in blister packs in 1 carton.

TAXOTERE concentrated solution requires dilution prior to use. A sterile, non-pyrogenic, single-dose diluent is supplied for that purpose. The diluent for TAXOTERE contains ethanol 95% v/v/water for injection (13/87 w/w), and is supplied in 1.5 mL (to be used with 20 mg TAXOTERE) and 6 mL (to be used with 80 mg TAXOTERE) vials.

Those with poor performance status, or otherwise non-life threatening indolent disease (such as relatively asymptomatic metastatic disease limited to the bone) should be considered as possible candidates for less toxic therapies prior to consideration of a TAXOTERE based therapy.

An analysis of safety data in patients equal or greater than 60 years of age showed an increase in the incidence of treatment-related grade 3 and 4 adverse events when treated with TAXOTERE in combination with Xeloda. Treatment-related serious adverse events and early withdrawals from treatment due to adverse events were lower in patients of less than 60 years of age.

Of the 332 patients treated with TAXOTERE every three weeks plus prednisone in the prostate cancer study (TAX327), 208 patients were 65 years of age or greater and 67 patients were older than 75 years. In patients treated with TAXOTERE every three weeks, the following TEAEs occurred at rates ≥10% higher in patients 65 years of age or greater compared to younger patients: anemia (71% vs 59%), infection (37% vs 24%), nail changes (34% vs 23%), anorexia (21% vs 10%), weight loss (15% vs 5%) respectively.

A dose reduction of Xeloda (capecitabine) to 75% is recommended when used in combination with docetaxel in patients with moderate renal impairment (please refer to Xeloda Product Monograph).

Neutropenia is the most frequently reported adverse event. Neutrophil nadirs occurred at a median of 7 days but this interval may be shorter in heavily pretreated patients. TAXOTERE therapy should not be administered until the neutrophil count is over 1500 cells/mm³. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent blood cell counts be performed on all patients receiving TAXOTERE. Patients should not be retreated with subsequent cycles of TAXOTERE until neutrophils recover to a level of >1500 cells/mm³. In cases of severe neutropenia (<500 cells/mm³) for seven days or more during a course of TAXOTERE therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate systematic measures are recommended (see Dosage and Administration).

TAXOTERE has been shown to be mutagenic in the in vitro chromosome aberration test in CHO-K1 cells and in the in vivo micronucleus test in the mouse.

The carcinogenic potential of TAXOTERE has not been studied. However, given that TAXOTERE is unequivocally genotoxic, it should be presumed to be a human carcinogen.

The development of severe peripheral neurotoxicity is infrequent and requires a reduction in dose (see Dosage and Administration). If symptoms persist, treatment should be discontinued.

Severe hypersensitivity reactions characterized by severe hypotension, bronchospasm, generalized rash/erythema or very rarely fatal anaphylaxis have been reported in patients who received premedication. These reactions resulted in immediate discontinuation in approximately 0.4% (5 of 1260) of patients. Severe symptoms resolve after discontinuation of the infusion and administration of appropriate therapy.

Patients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of TAXOTERE, thus facilities for the treatment of hypotension and bronchospasm should be available. Severe reactions require immediate discontinuation of TAXOTERE and aggressive therapy. Patients who have developed severe hypersensitivity reactions should not be rechallenged with TAXOTERE. If minor reactions such as flushing or localized skin reactions occur, therapy with TAXOTERE does not have to be discontinued. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of TAXOTERE (see Dosage and Administration).

All patients should be premedicated with an oral corticosteroid such as dexamethasone 16 mg per day (e.g., 8 mg BID) for 3 days starting one day prior to TAXOTERE administration to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.

The pretreatment regimen for prostate cancer (given the concurrent use of prednisone or prednisolone) is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the TAXOTERE infusion (see Dosage and Administration, Premedication).

Localized erythema of the extremities (palm of the hands and soles of the feet) with edema, followed by desquamation has been observed. In case of severe skin toxicity during a course of TAXOTERE therapy, a reduction in dose for subsequent courses of therapy is recommended (see Dosage and Administration).

Severe fluid retention has been reported following TAXOTERE therapy. Therefore, patients should be premedicated with oral corticosteroids prior to each TAXOTERE administration to reduce the incidence and severity of fluid retention (see Dosage and Administration). Patients with preexisting severe fluid retention such as pleural effusion, pericardial effusion and ascites should be closely monitored from the first dose for the possible exacerbation of the effusions.

Treatment related acute myeloid leukemia may occur. In the adjuvant breast cancer trial (TAX316) at a median follow-up of 83 months, 3 of 744 women who received TAXOTERE, doxorubicin and cyclophosphamide (TAC) were diagnosed with AML and one additional patient was diagnosed with suspected MDS. One of 736 women who received 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) in the other arm of this study was diagnosed with AML.

In patients treated with TAXOTERE, doxorubicin and cyclophosphamide (TAC) as adjuvant therapy for breast cancer, the risk of delayed myelodysplasia or myeloid leukemia requires hematological follow-up (see Adverse Reactions).

The safety and effectiveness of TAXOTERE in children have not been established.

TAXOTERE may cause fetal harm when administered to a pregnant woman. There is no information on the use of TAXOTERE during pregnancy. No evidence of teratogenic effect was found when TAXOTERE was administered at 1.8 or 1.2 mg/m²/day, in rats or rabbits, respectively. However, TAXOTERE has been shown to be both embryotoxic and fetotoxic in rabbits and rats—causing intrauterine mortality, reduced fetal weight and fetal ossification delays—and to reduce fertility in rats. These effects are consistent with maternal toxicity. As with other cytotoxic drugs, TAXOTERE may cause fetal harm when administered to pregnant women. Therefore, TAXOTERE must not be used during pregnancy. Women of childbearing age and receiving TAXOTERE should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur. Should TAXOTERE be used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus.

It is not known whether TAXOTERE is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from TAXOTERE, it is recommended that women be advised not to breast-feed during TAXOTERE therapy.

In patients treated with TAXOTERE at 100 mg/m² as a single agent who have transaminase (ALT and/or AST) greater than 1.5 times the upper limit of normal (ULN) concurrent with alkaline phosphatase greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal hemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia. If TAXOTERE is considered essential for a patient with above specified hepatic function impairment, the recommended dose of TAXOTERE in patients with elevated liver function test (LFTs) is 75 mg/m² and LFTs should be measured at baseline and before each cycle (see Dosage and Administration).

No data are available in patients with hepatic impairment treated by TAXOTERE in combination.

Unopened vials of TAXOTERE (docetaxel for injection) are stable until the expiration date indicated on the package when stored between 2 and 25°C and protected from light. Freezing does not adversely affect the product.

Store the unopened vials between 2-25°C. Retain in the original package to protect from bright light.

TAXOTERE premix solution (10 mg docetaxel/mL) should be used as soon as possible after preparation. However the chemical and physical stability of the premix solution has been demonstrated stable for 8 hours when stored either between 2 and 8°C or at room temperature.

TAXOTERE infusion solutions, if stored between 2 and 25°C is stable for 4 hours. Fully prepared TAXOTERE infusion solution (in either 0.9% sodium chloride solution or 5% dextrose solution) should be used within 4 hours (including the 1 hour i.v. administration).

At doses of 70-115 mg/m², the kinetic profile of TAXOTERE is dose independent and consistent with a three-compartment pharmacokinetic model, with half lives for the α, β and γ phases of 4 min, 36 min and 11.1 h, respectively. Mean values for total body clearance and steady state volume of distribution were 21 L/h/m² and 113 L, respectively.

A population pharmacokinetic analysis has been performed in patients receiving TAXOTERE. Pharmacokinetic parameters estimated by the model were very close to those estimated from Phase I studies. The pharmacokinetics of TAXOTERE were not altered by the age or sex of the patient. In a small number of patients with clinical chemistry data suggestive of mild to moderate liver function impairment (ALT, AST ≥1.5 times the upper limit of normal associated with alkaline phosphatase ≥2.5 times the upper limit of normal), total clearance was lowered by 27% on average (see Dosage and Administration).

The effect of daily oral prednisone administration on the pharmacokinetics of TAXOTERE administered with dexamethasone premedication prior to infusion has been evaluated in 42 patients treated for prostate cancer. No effect of prednisone on the pharmacokinetics of TAXOTERE was observed.

Based on in vitro studies, isoenzymes of the cytochrome P450-3A subfamily appear to be involved in TAXOTERE metabolism.

TAXOTERE is more than 95% protein bound. Dexamethasone does not affect the protein binding of TAXOTERE.

TAXOTERE (docetaxel for injection) is an antineoplastic agent, which acts by disrupting the microtubular network in cells that is essential for vital mitotic and interphase cellular functions. TAXOTERE promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. TAXOTERE binds to free tubulin thereby decreasing the critical intracellular concentration of tubulin. The promoted polymerization of microtubules leads to the production of microtubule bundles without normal function and to the stabilization of microtubules, resulting in the inhibition of mitosis in cells. The binding of TAXOTERE to microtubules does not alter the number of protofilaments in the bound microtubules; in that, it differs from other spindle poisons.

TAXOTERE was found to be cytotoxic in vitro against various murine and human tumor cell lines, and against freshly excised human tumor cells in clonogenic assays.

In addition, TAXOTERE was found to be active on a number of cell lines overexpressing the p-glycoprotein, which is encoded by the multidrug resistant gene.