The incidence of treatment-related mortality associated with docetaxel 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 docetaxel as a single agent at a dose of 100 mg/m 2 [see Warnings and Precautions (5.1) ]. Docetaxel Injection should ...
Docetaxel Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. Docetaxel Injection as a single agent is indicated for the treatment of patients with locally advan...
For all indications, toxicities may warrant dosage adjustments [see Dosage and Administration (2.7) ]. Administer in a facility equipped to manage possible complications (e.g. anaphylaxis). • For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of Docetaxel Injection is 60 mg/m 2 to 100 mg/m 2 administered intravenously over 1 hour every 3 weeks. • For the adju...
One-vial formulation (Injection) Docetaxel Injection is supplied in single dose and multiple dose vials as a sterile, pyrogen-free, non-aqueous solution. Docetaxel Injection 80 mg/4 mL: The vial is in one carton. NDC 63739-971-17 Docetaxel Injection 20 mg/mL: The vial is in one carton. NDC 63739-932-11 Two-vial formulation (Injection with Diluent) Store at 25°C (77°F); excursions permitted from 15°C - 30°C (59°-...
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www.osha.gov/SLTC/hazardousdrugs/index.htmlThe incidence of treatment-related mortality associated with docetaxel 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 docetaxel as a single agent at a dose of 100 mg/m 2 [see Warnings and Precautions (5.1)].
Docetaxel Injection should not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × 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 × 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 Docetaxel Injection therapy [see Warnings and Precautions (5.2)].
Docetaxel Injection therapy should not be given to patients with neutrophil counts of <1500 cells/mm 3. 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 Docetaxel Injection . [see Warnings and Precautions (5.3)].
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received a 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and administration of appropriate therapy [see Warnings and Precautions (5.4)] . Docetaxel Injection must not be given to patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80 [see Contraindications (4)] .
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) [see Warnings and Precautions (5.5)].
Docetaxel Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
Docetaxel Injection as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum based chemotherapy.
Docetaxel Injection in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.
Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
Docetaxel Injection 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.
Docetaxel Injection 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).
For all indications, toxicities may warrant dosage adjustments [see Dosage and Administration (2.7)].
Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
Breast Cancer
Patients who are dosed initially at 100 mg/m 2 and who experience either febrile neutropenia, neutrophils <500 cells/mm 3 for more than 1 week, or severe or cumulative cutaneous reactions during Docetaxel Injection therapy should have the dosage adjusted from 100 mg/m 2 to 75 mg/m 2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m 2 to 55 mg/m 2 or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m 2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm 3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Docetaxel Injection therapy may tolerate higher doses. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
Combination Therapy with Docetaxel Injection in the Adjuvant Treatment of Breast Cancer
Docetaxel Injection in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm 3. Patients 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 Docetaxel Injection dose reduced to 60 mg/m 2. Patients who experience grade 3 or 4 stomatitis should have their Docetaxel Injection dose decreased to 60 mg/m 2. Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have their dosage of Docetaxel Injection reduced from 75 mg/m 2 to 60 mg/m 2. If the patient continues to experience these reactions at 60 mg/m , treatment should be discontinued.
Non-Small Cell Lung Cancer
Monotherapy with Docetaxel Injection for NSCLC treatment after failure of prior platinum-based chemotherapy
Patients who are dosed initially at 75 mg/m 2 and who experience either febrile neutropenia, neutrophils <500 cells/mm 3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during Docetaxel Injection treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m 2. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
Combination therapy with Docetaxel Injection for chemotherapy-naïve NSCLC
For patients who are dosed initially at Docetaxel Injection 75 mg/m 2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm 3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the Docetaxel Injection dosage in subsequent cycles should be reduced to 65 mg/m 2. In patients who require a further dose reduction, a dose of 50 mg/m 2 is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.
Prostate Cancer
Combination therapy with Docetaxel Injection for hormone-refractory metastatic prostate cancer
Docetaxel Injection should be administered when the neutrophil count is ≥1,500 cells/mm 3. Patients who experience either febrile neutropenia, neutrophils < 500 cells/mm 3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have the dosage of Docetaxel Injection reduced from 75 mg/m 2 to 60 mg/m 2. If the patient continues to experience these reactions at 60 mg/m 2, the treatment should be discontinued.
Gastric or Head and Neck Cancer
Docetaxel Injection in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer
Patients treated with Docetaxel Injection in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the Docetaxel Injection dose should be reduced from 75 mg/m 2 to 60 mg/m 2. If subsequent episodes of complicated neutropenia occur the Docetaxel Injection dose should be reduced from 60 mg/m 2 to 45 mg/m 2. In case of grade 4 thrombocytopenia the Docetaxel Injection dose should be reduced from 75 mg/m 2 to 60 mg/m 2. Patients should not be retreated with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1,500 cells/mm 3 and platelets recover to a level >100,000 cells/mm 3. Discontinue treatment if these toxicities persist. [see Warnings and Precautions (5.3)].
Recommended dose modifications for toxicities in patients treated with Docetaxel Injection in combination with cisplatin and fluorouracil are shown in Table 1.
| Toxicity | Dosage adjustment |
|---|---|
Diarrhea grade 3 | First episode: reduce fluorouracil dose by 20%. |
Diarrhea grade 4 | First episode: reduce Docetaxel Injection and fluorouracil doses by 20%. |
Stomatitis/mucositis grade 3 | First episode: reduce fluorouracil dose by 20%. |
Stomatitis/mucositis grade 4 | First episode: stop fluorouracil only, at all subsequent cycles. |
Liver dysfunction:
In case of AST/ALT >2.5 to ≤5 x ULN and AP ≤2.5 x ULN, or AST/ALT >1.5 to ≤5 x ULN and AP >2.5 to ≤5 x ULN, Docetaxel Injection should be reduced by 20%.
In case of AST/ALT >5 x ULN and/or AP >5 x ULN Docetaxel Injection should be stopped.
The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below:
Cisplatin dose modifications and delays
Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCIC-CTC grade:
• Grade 2: Reduce cisplatin dose by 20%.
• Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.
Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 x normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).
For other cisplatin dosage adjustments, also refer to the manufacturers’ prescribing information.
| Creatinine clearance result before next cycle | Cisplatin dose next cycle | ||
|---|---|---|---|
| CrCl = Creatinine clearance | |||
CrCl ≥60 mL/min | Full dose of cisplatin was given. CrCl was to be repeated before each treatment cycle. | ||
Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle. | |||
CrCl between 40 and 59 mL/min | |||
If no recovery was observed, then cisplatin was omitted from the next treatment cycle. | |||
Dose of cisplatin was omitted in that treatment cycle only.
| |||
If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued. | |||
CrCl <40 mL/min | |||
If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle. | |||
If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle. | |||
Fluorouracil dose modifications and treatment delays
For diarrhea and stomatitis, see Table 1.
In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.
For other >grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤1 and then recommenced, if medically appropriate.
For other fluorouracil dosage adjustments, also refer to the manufacturers’ prescribing information.
Combination Therapy with Strong CYP3A4 inhibitors:
Docetaxel Injection is a cytotoxic anticancer drug. Follow special handling and disposal procedures when preparing Docetaxel Injection solutions. 1
If Docetaxel Injection, initial diluted solution, or final dilution for infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If Docetaxel Injection, initial diluted solution, or final dilution for infusion should come into contact with mucosa, immediately and thoroughly wash with water.
Contact of the Docetaxel Injection with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the final Docetaxel Injection dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
Two-vial formulation (Injection with Diluent)
Docetaxel Injection requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the Docetaxel Injection and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL docetaxel.
The table below provides the fill range of the Diluent, the approximate extractable volume of Diluent when the entire contents of the diluent vial are withdrawn, and the concentration of the initial diluted solution for Docetaxel Injection 20 mg and Docetaxel Injection 80 mg (see Table 3).
| Product | Diluent 13% (w/v) polyethylene glycol 400 in water for injection Fill Range (mL) | Approximate extractable volume of Diluent when entire contents are withdrawn (mL) | Concentration of the initial diluted solution (mg/mL docetaxel) |
|---|---|---|---|
Docetaxel Injection | 1.5 to 2.08 mL | 1.95 mL | 10 mg/mL |
Docetaxel Injection | 6 to 7.4 mL | 7.2 mL | 10 mg/mL |
One-vial formulation (Injection)
Docetaxel Injection requires NO prior dilution with a diluent and is ready to add to the infusion solution.
Please follow the preparation instructions provided below.
DO NOT use the two-vial formulation (Injection with diluent) with the one-vial formulation.
Two-vial formulation (Injection with Diluent)
A.Initial Diluted Solution
B.Final Dilution for Infusion
One-vial formulation (Injection)
Docetaxel Injection (20 mg/mL) requires NO prior dilution with a diluent and is ready to add to the infusion solution. Use only a 21 gauge needle to withdraw docetaxel from the vial because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber particulates.
The docetaxel dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature (below 25°C) and lighting conditions.
Docetaxel Injection final dilution for infusion, if stored between 2°C and 25°C (36°F and 77°F) is stable for 4 hours. Docetaxel Injection final dilution for infusion (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour intravenous administration).
Two-vial formulation (Injection with Diluent)
Docetaxel Injection 80 mg/2 mL solution in single dose vial with Diluent for Docetaxel Injection USP 80 mg. Both items are in a blister pack in one carton.
Docetaxel Injection 20 mg/0.5 mL solution in single dose vial with Diluent for Docetaxel Injection USP 20 mg. Both items are in a blister pack in one carton.
One-vial formulation (Injection in Single Dose and Multiple Dose Vials)
Docetaxel Injection: 160 mg/8 mL solution
Docetaxel Injection: 80 mg/4 mL solution
Docetaxel Injection: 20 mg/1 mL solution
Breast Cancer
Docetaxel administered at 100 mg/m 2 was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m 2, mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths.
Non-Small Cell Lung Cancer
Docetaxel administered at a dose of 100 mg/m 2 in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m 2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m 2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration (2.2), Clinical Studies (14)].
Patients with combined abnormalities of transaminases and alkaline phosphatase should not be treated with Docetaxel Injection [see Boxed Warning, Use in Specific Populations (8.6), Clinical studies (14)].
Perform frequent peripheral blood cell counts on all patients receiving Docetaxel Injection. Patients should not be retreated with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm 3 and platelets recover to a level >100,000 cells/mm 3.
A 25% reduction in the dose of Docetaxel Injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm 3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a Docetaxel Injection cycle [see Dosage and Administration (2.7)].
Neutropenia (<2000 neutrophils/mm 3) occurs in virtually all patients given 60 mg/m 2 to 100 mg/m 2 of docetaxel and grade 4 neutropenia (<500 cells/mm 3) occurs in 85% of patients given 100 mg/m 2 and 75% of patients given 60 mg/m 2. Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel Injection should not be administered to patients with neutrophils <1500 cells/mm 3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m 2 but was very uncommon in patients given 60 mg/m 2. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions (6.1), Clinical Studies (14)].
Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [see Dosage and Administration (2.7), Adverse Reactions (6)]
Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and aggressive therapy. Patients with a history of severe hypersensitivity reactions should not be rechallenged with Docetaxel Injection.
Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel Injection [see Dosage and Administration (2.6)]
Severe fluid retention has been reported following docetaxel therapy. Patients should be premedicated with oral corticosteroids prior to each Docetaxel Injection administration to reduce the incidence and severity of fluid retention [see Dosage and Administration (2.6)]. Patients with pre-existing effusions should be closely monitored from the first dose for the possible exacerbation of the effusions.
When fluid retention occurs, peripheral edema usually starts in the lower extremities and may become generalized with a median weight gain of 2 kg.
Among 92 breast cancer patients premedicated with 3-day corticosteroids, moderate fluid retention occurred in 27.2% and severe fluid retention in 6.5%. The median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m 2. Nine of 92 patients (9.8%) of patients discontinued treatment due to fluid retention: 4 patients discontinued with severe fluid retention; the remaining 5 had mild or moderate fluid retention. The median cumulative dose to treatment discontinuation due to fluid retention was 1021 mg/m 2. Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, e.g., salt restriction, oral diuretic(s).
Treatment-related acute myeloid leukemia (AML) or myelodysplasia has occurred in patients given anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. In the adjuvant breast cancer trial (TAX316) AML occurred in 3 of 744 patients who received docetaxel, doxorubicin and cyclophosphamide (TAC) and in 1 of 736 patients who received fluorouracil, doxorubicin and cyclophosphamide [see Clinical Studies (14.2)]. In TAC-treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires hematological follow-up.
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 [see Dosage and Administration (2.7)]. The discontinuation rate due to skin toxicity was 1.6% (15/965) for metastatic breast cancer patients. Among 92 breast cancer patients premedicated with 3-day corticosteroids, there were no cases of severe skin toxicity reported and no patient discontinued docetaxel due to skin toxicity.
Severe neurosensory symptoms (e.g. 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 [see Dosage and Administration (2.7)]. Patients who experienced neurotoxicity in clinical trials and for whom follow-up information on the complete resolution of the event was available had spontaneous reversal of symptoms with a median of 9 weeks from onset (range: 0 to 106 weeks). Severe peripheral motor neuropathy mainly manifested as distal extremity weakness occurred in 4.4% (42/965).
Cystoid macular edema (CME) has been reported in patients treated with Docetaxel Injection. Patients with impaired vision should undergo a prompt and comprehensive ophthalmologic examination. If CME is diagnosed, Docetaxel Injection treatment should be discontinued and appropriate treatment initiated. Alternative non-taxane cancer treatment should be considered.
Severe asthenia has been reported in 14.9% (144/965) of metastatic breast cancer patients but has 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.
Cases of intoxication have been reported with some formulations of docetaxel due to the alcohol content. The alcohol content in a dose of Docetaxel Injection may affect the central nervous system and should be taken into account for patients in whom alcohol intake should be avoided or minimized. Consideration should be given to the alcohol content in Docetaxel Injection on the ability to drive or use machines immediately after the infusion.
For Two-vial formulation (Injection with Diluent)
Each administration of Docetaxel Injection at 100 mg/m 2 delivers 0.15 g/m 2of ethanol. For a patient with a BSA of 2.0 m 2, this would deliver 0.3 grams of ethanol [ see Description (11)
]. Other docetaxel products may have a different amount of alcohol.
For One-vial formulation (Injection)
Each administration of Docetaxel Injection at 100 mg/m 2 delivers 1.975 g/m 2 of ethanol. For a patient with a BSA of 2.0 m 2, this would deliver 3.95 grams of ethanol [ see Description (11)
]. Other docetaxel products may have a different amount of alcohol.
Docetaxel Injection can cause fetal harm when administered to a pregnant woman. Docetaxel caused embryofetal toxicities including intrauterine mortality when administered to pregnant rats and rabbits during the period of organogenesis. Embryofetal effects in animals occurred at doses as low as 1/50 and 1/300 the recommended human dose on a body surface area basis.
There are no adequate and well-controlled studies in pregnant women using Docetaxel Injection. If Docetaxel Injection is 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. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Docetaxel Injection [see Use in Specific Populations (8.1)].
The most serious adverse reactions from docetaxel are:
The most common adverse reactions across all docetaxel 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. Incidence varies depending on the indication.
Adverse reactions are described according to indication. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established.
Breast Cancer
Monotherapy with docetaxel for locally advanced or metastatic breast cancer after failure of prior chemotherapy
Docetaxel 100 mg/m 2: Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received docetaxel administered at 100 mg/m 2 as a 1-hour infusion every 3 weeks: 2045 patients with various tumor types and normal baseline liver function tests; the subset of 965 patients with locally advanced or metastatic breast cancer, both previously treated and untreated with chemotherapy, who had normal baseline liver function tests; and an additional 61 patients with various tumor types who had abnormal liver function tests at baseline. These reactions were described using COSTART terms and were considered possibly or probably related to docetaxel. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving docetaxel for the treatment of breast cancer and in patients with other tumor types (See Table 4).
| Adverse Reaction | All Tumor Types Normal LFTs * n=2045 % | All Tumor Types Elevated LFTs † n=61 % | Breast Cancer Normal LFTs n=965 % |
|---|---|---|---|
Hematologic | |||
Neutropenia | |||
<2000 cells/mm 3 | 96 | 96 | 99 |
<500 cells/mm 3 | 75 | 88 | 86 |
Leukopenia | |||
<4000 cells/mm 3 | 96 | 98 | 99 |
<1000 cells/mm 3 | 32 | 47 | 44 |
Thrombocytopenia | |||
<100,000 cells/mm 3 | 8 | 25 | 9 |
Anemia | |||
<11 g/dL | 90 | 92 | 94 |
<8 g/dL | 9 | 31 | 8 |
Febrile Neutropenia ‡ | 11 | 26 | 12 |
Septic Death | 2 | 5 | 1 |
Non-Septic Death | 1 | 7 | 1 |
Infections | |||
Any | 22 | 33 | 22 |
Severe | 6 | 16 | 6 |
Fever in Absence of Infection | |||
Any | 31 | 41 | 35 |
Severe | 2 | 8 | 2 |
Hypersensitivity Reactions | |||
Regardless of Premedication | |||
Any | 21 | 20 | 18 |
Severe | 4 | 10 | 3 |
With 3-day Premedication | n=92 | n=3 | n=92 |
Any | 15 | 33 | 15 |
Severe | 2 | 0 | 2 |
Fluid Retention | |||
Regardless of Premedication | |||
Any | 47 | 39 | 60 |
Severe | 7 | 8 | 9 |
With 3-day Premedication | n=92 | n=3 | n=92 |
Any | 64 | 67 | 64 |
Severe | 7 | 33 | 7 |
Neurosensory | |||
Any | 49 | 34 | 58 |
Severe | 4 | 0 | 6 |
Cutaneous | |||
Any | 48 | 54 | 47 |
Severe | 5 | 10 | 5 |
Nail Changes | |||
Any | 31 | 23 | 41 |
Severe | 3 | 5 | 4 |
Gastrointestinal | |||
Nausea | 39 | 38 | 42 |
Vomiting | 22 | 23 | 23 |
Diarrhea | 39 | 33 | 43 |
Severe | 5 | 5 | 6 |
Stomatitis | |||
Any | 42 | 49 | 52 |
Severe | 6 | 13 | 7 |
Alopecia | 76 | 62 | 74 |
Asthenia | |||
Any | 62 | 53 | 66 |
Severe | 13 | 25 | 15 |
Myalgia | |||
Any | 19 | 16 | 21 |
Severe | 2 | 2 | 2 |
Arthralgia | 9 | 7 | 8 |
Infusion Site Reactions | 4 | 3 | 4 |
* Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
† Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
‡ Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization
Hematologic Reactions
Reversible marrow suppression was the major dose-limiting toxicity of docetaxel [see Warnings and Precautions (5.3)]. The median time to nadir was 7 days, while the median duration of severe neutropenia (<500 cells/mm 3) was 7 days. Among 2045 patients with solid tumors and normal baseline LFTs, severe neutropenia occurred in 75.4% and lasted for more than 7 days in 2.9% of cycles.
Febrile neutropenia (<500 cells/mm 3 with fever >38°C with intravenous antibiotics and/or hospitalization) occurred in 11% of patients with solid tumors, in 12.3% of patients with metastatic breast cancer, and in 9.8% of 92 breast cancer patients premedicated with 3-day corticosteroids.
Severe infectious episodes occurred in 6.1% of patients with solid tumors, in 6.4% of patients with metastatic breast cancer, and in 5.4% of 92 breast cancer patients premedicated with 3-day corticosteroids. Thrombocytopenia (<100,000 cells/mm3) associated with fatal gastrointestinal hemorrhage has been reported.
Hypersensitivity Reactions
Severe hypersensitivity reactions have been reported [see Boxed Warning, Warnings and Precautions (5.4)] . Minor events, including flushing, rash with or without pruritus, chest tightness, back pain, dyspnea, drug fever, or chills, have been reported and resolved after discontinuing the infusion and instituting appropriate therapy.
Fluid Retention
Fluid retention can occur with the use of docetaxel [see Boxed Warning, Dosage and Administration (2.6), Warnings and Precautions (5.5)].
Cutaneous Reactions
Severe skin toxicity is discussed elsewhere in the label [see Warnings and Precautions (5.7)]. Reversible cutaneous reactions characterized by a rash including localized eruptions, mainly on the feet and/or hands, but also on the arms, face, or thorax, usually associated with pruritus, have been observed. Eruptions generally occurred within 1 week after docetaxel infusion, recovered before the next infusion, and were not disabling.
Severe nail disorders were characterized by hypo- or hyperpigmentation, and occasionally by onycholysis (in 0.8% of patients with solid tumors) and pain.
Neurologic Reactions
Neurologic reactions are discussed elsewhere in the label [see Warnings and Precautions (5.8) ].
Gastrointestinal Reactions
Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3 to 5% of patients with solid tumors and to a similar extent among metastatic breast cancer patients. The incidence of severe reactions was 1% or less for the 92 breast cancer patients premedicated with 3-day corticosteroids.
Severe stomatitis occurred in 5.5% of patients with solid tumors, in 7.4% of patients with metastatic breast cancer, and in 1.1% of the 92 breast cancer patients premedicated with 3-day corticosteroids.
Cardiovascular Reactions
Hypotension occurred in 2.8% of patients with solid tumors; 1.2% required treatment. Clinically meaningful events such as heart failure, sinus tachycardia, atrial flutter, dysrhythmia, unstable angina, pulmonary edema, and hypertension occurred rarely. Seven of 86 (8.1%) of metastatic breast cancer patients receiving docetaxel 100 mg/m 2 in a randomized trial and who had serial left ventricular ejection fractions assessed developed deterioration of LVEF by ≥10% associated with a drop below the institutional lower limit of normal.
Infusion Site Reactions
Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, extravasation, or swelling of the vein.
Hepatic Reactions
In patients with normal LFTs at baseline, bilirubin values > the ULN occurred in 8.9% of patients. Increases in AST or ALT >1.5 times the ULN, or alkaline phosphatase >2.5 times ULN, were observed in 18.9% and 7.3% of patients, respectively. While on docetaxel, increases in AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN occurred in 4.3% of patients with normal LFTs at baseline. Whether these changes were related to the drug or underlying disease has not been established.
Hematologic and other toxicity is increased at higher doses and in patients with elevated baseline liver function tests (LFTs). In the following tables, adverse drug reactions are compared for three populations: 730 patients with normal LFTs given docetaxel at 100 mg/m 2 in the randomized and single arm studies of metastatic breast cancer after failure of previous chemotherapy; 18 patients in these studies who had abnormal baseline LFTs (defined as AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN); and 174 patients in Japanese studies given docetaxel at 60 mg/m 2 who had normal LFTs (see Tables 5 and 6).
| Docetaxel 100 mg/m 2 | Docetaxel 60 mg/m 2 | ||
|---|---|---|---|
| Normal LFTs * | Elevated LFTs † | Normal LFTs | |
| Adverse Reaction | n=730 | n=18 | n=174 |
| % | % | % | |
Neutropenia | |||
Any <2000 cells/mm 3 | 98 | 100 | 95 |
Grade 4 <500 cells/mm 3 | 84 | 94 | 75 |
Thrombocytopenia | |||
Any <100,000 cells/mm 3 | 11 | 44 | 14 |
Grade 4 <20,000 cells/mm 3 | 1 | 17 | 1 |
Anemia (<11 g/dL) | 95 | 94 | 65 |
Infection ‡ | |||
Any | 23 | 39 | 1 |
Grade 3 and 4 | 7 | 33 | 0 |
Febrile Neutropenia § | |||
By Patient | 12 | 33 | 0 |
By Course | 2 | 9 | 0 |
Septic Death | 2 | 6 | 1 |
Non-Septic Death | 1 | 11 | 0 |
* Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
† Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
‡ Incidence of infection requiring hospitalization and/or intravenous antibiotics was 8.5% (n=62) among the 730 patients with normal LFTs at baseline; 7 patients had concurrent grade 3 neutropenia, and 46 patients had grade 4 neutropenia.
§ Febrile Neutropenia: For 100 mg/m 2, ANC grade 4 and fever >38°C with intravenous antibiotics and/or hospitalization; for 60 mg/m 2, ANC grade 3/4 and fever >38.1°C
| Docetaxel 100 mg/m 2 | Docetaxel 60 mg/m 2 | ||||||
|---|---|---|---|---|---|---|---|
| Normal LFTs * | Elevated LFTs † | Normal LFTs | |||||
| Adverse Reaction | n=730 | n=18 | n=174 | ||||
| % | % | % | |||||
| NA = not available | |||||||
Acute Hypersensitivity | |||||||
Any | 13 | 6 | 1 | ||||
Severe | 1 | 0 | 0 | ||||
Fluid Retention ‡ | |||||||
Any | 56 | 61 | 13 | ||||
Severe | 8 | 17 | 0 | ||||
Neurosensory | |||||||
Any | 57 | 50 | 20 | ||||
Severe | 6 | 0 | 0 | ||||
Myalgia | 23 | 33 | 3 | ||||
Cutaneous | |||||||
Any | 45 | 61 | 31 | ||||
Severe | 5 | 17 | 0 | ||||
Asthenia | |||||||
Any | 65 | 44 | 66 | ||||
Severe | 17 | 22 | 0 | ||||
Diarrhea | |||||||
Any | 42 | 28 | NA | ||||
Severe | 6 | 11 | |||||
Stomatitis | |||||||
Any | 53 | 67 | 19 | ||||
Severe | 8 | 39 | 1 | ||||
* Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
† Elevated Baseline Liver Function: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
‡ Fluid Retention includes (by COSTART): edema (peripheral, localized, generalized, lymphedema, pulmonary edema, and edema otherwise not specified) and effusion (pleural, pericardial, and ascites); no premedication given with the 60 mg/m 2 dose
In the three-arm monotherapy trial, TAX313, which compared docetaxel 60 mg/m 2 , 75 mg/m 2 and 100 mg/m 2 in advanced breast cancer, grade 3/4 or severe adverse reactions occurred in 49.0% of patients treated with docetaxel 60 mg/m 2 compared to 55.3% and 65.9% treated with 75 mg/m 2 and 100 mg/m 2 respectively. Discontinuation due to adverse reactions was reported in 5.3% of patients treated with 60 mg/m 2 vs. 6.9% and 16.5% for patients treated at 75 mg/m 2 and 100 mg/m 2 respectively. Deaths within 30 days of last treatment occurred in 4.0% of patients treated with 60 mg/m 2 compared to 5.3% and 1.6% for patients treated at 75 mg/m 2 and 100 mg/m 2 respectively.
Combination therapy with docetaxel in the adjuvant treatment of breast cancer
The following table presents treatment emergent adverse reactions observed in 744 patients, who were treated with docetaxel 75 mg/m 2 every 3 weeks in combination with doxorubicin and cyclophosphamide (see Table 7).
| Docetaxel 75 mg/m 2+ Doxorubicin 50 mg/m 2+ Cyclophosphamide 500 mg/m 2 (TAC) n=744 % | Fluorouracil 500 mg/m 2+ Doxorubicin 50 mg/m 2+ Cyclophosphamide 500 mg/m 2 (FAC) n=736 % | |||
|---|---|---|---|---|
| Adverse Reaction | Any | Grade 3/4 | Any | Grade 3/4 |
Anemia | 92 | 4 | 72 | 2 |
Neutropenia | 71 | 66 | 82 | 49 |
Fever in absence of infection | 47 | 1 | 17 | 0 |
Infection | 39 | 4 | 36 | 2 |
Thrombocytopenia | 39 | 2 | 28 | 1 |
Febrile neutropenia | 25 | N/A | 3 | N/A |
Neutropenic infection | 12 | N/A | 6 | N/A |
Hypersensitivity reactions | 13 | 1 | 4 | 0 |
Lymphedema | 4 | 0 | 1 | 0 |
Fluid Retention * | 35 | 1 | 15 | 0 |
Peripheral edema | 27 | 0 | 7 | 0 |
Weight gain | 13 | 0 | 9 | 0 |
Neuropathy sensory | 26 | 0 | 10 | 0 |
Neuro-cortical | 5 | 1 | 6 | 1 |
Neuropathy motor | 4 | 0 | 2 | 0 |
Neuro-cerebellar | 2 | 0 | 2 | 0 |
Syncope | 2 | 1 | 1 | 0 |
Alopecia | 98 | N/A | 97 | N/A |
Skin toxicity | 27 | 1 | 18 | 0 |
Nail disorders | 19 | 0 | 14 | 0 |
Nausea | 81 | 5 | 88 | 10 |
Stomatitis | 69 | 7 | 53 | 2 |
Vomiting | 45 | 4 | 59 | 7 |
Diarrhea | 35 | 4 | 28 | 2 |
Constipation | 34 | 1 | 32 | 1 |
Taste perversion | 28 | 1 | 15 | 0 |
Anorexia | 22 | 2 | 18 | 1 |
Abdominal Pain | 11 | 1 | 5 | 0 |
Amenorrhea | 62 | N/A | 52 | N/A |
Cough | 14 | 0 | 10 | 0 |
Cardiac dysrhythmias | 8 | 0 | 6 | 0 |
Vasodilatation | 27 | 1 | 21 | 1 |
Hypotension | 2 | 0 | 1 | 0 |
Phlebitis | 1 | 0 | 1 | 0 |
Asthenia | 81 | 11 | 71 | 6 |
Myalgia | 27 | 1 | 10 | 0 |
Arthralgia | 19 | 1 | 9 | 0 |
Lacrimation disorder | 11 | 0 | 7 | 0 |
Conjunctivitis | 5 | 0 | 7 | 0 |
* COSTART term and grading system for events related to treatment.
Of the 744 patients treated with TAC, 36.3% experienced severe treatment emergent adverse reactions compared to 26.6% of the 736 patients treated with FAC. Dose reductions due to hematologic toxicity occurred in 1% of cycles in the TAC arm versus 0.1% of cycles in the FAC arm. Six percent of patients treated with TAC discontinued treatment due to adverse reactions, 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 patients died in each arm within 30 days of their last study treatment; 1 death per arm was attributed to study drugs.
Fever and Infection
Fever in the absence of infection was seen in 46.5% of TAC-treated patients and in 17.1% of FAC-treated patients. Grade 3/4 fever in the absence of infection was seen in 1.3% and 0% of TAC- and FAC-treated patients respectively. Infection was seen in 39.4% of TAC-treated patients compared to 36.3% of FAC-treated patients. Grade 3/4 infection was seen in 3.9% and 2.2% of TAC-treated and FAC-treated patients respectively. There were no septic deaths in either treatment arm.
Gastrointestinal Reactions
In addition to gastrointestinal reactions reflected in the table above, 7 patients in the TAC arm were reported to have colitis/enteritis/large intestine perforation vs. one patient in the FAC arm. Five of the 7 TAC-treated patients required treatment discontinuation; no deaths due to these events occurred.
Cardiovascular Reactions
More cardiovascular reactions were reported in the TAC arm vs. the FAC arm; dysrhythmias, all grades (7.9% vs. 6.0%), hypotension, all grades (2.6% vs. 1.1%) and CHF (2.3% vs. 0.9%, at 70 months median follow-up). One patient in each arm died due to heart failure.
Acute Myeloid Leukemia (AML)
Treatment-related acute myeloid leukemia or myelodysplasia is known to occur in patients treated with anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. AML occurs at a higher frequency when these agents are given in combination with radiation therapy. AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at 5 years in TAX316 was 0.4% for TAC treated patients and 0.1% for FAC-treated patients. This risk of AML is comparable to the risk observed for other anthracyclines/cyclophosphamide containing adjuvant breast chemotherapy regimens.
Lung Cancer
Monotherapy with docetaxel for unresectable, locally advanced or metastatic NSCLC previously treated with platinum-based chemotherapy
Treatment emergent adverse drug reactions are shown in Table 8. Included in this table are safety data for a total of 176 patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who were treated in two randomized, controlled trials. These reactions were described using NCI Common Toxicity Criteria regardless of relationship to study treatment, except for the hematologic toxicities or where otherwise noted.
| Adverse Reaction | Docetaxel 75 mg/m 2 n=176 % | Best Supportive Care n=49 % | Vinorelbine/Ifosfamide n=119 % |
|---|---|---|---|
Neutropenia | |||
Any | 84 | 14 | 83 |
Grade 3/4 | 65 | 12 | 57 |
Leukopenia | |||
Any | 84 | 6 | 89 |
Grade 3/4 | 49 | 0 | 43 |
Thrombocytopenia | |||
Any | 8 | 0 | 8 |
Grade 3/4 | 3 | 0 | 2 |
Anemia | |||
Any | 91 | 55 | 91 |
Grade 3/4 | 9 | 12 | 14 |
Febrile Neutropenia† | 6 | NA ‡ | 1 |
Infection | |||
Any | 34 | 29 | 30 |
Grade 3/4 | 10 | 6 | 9 |
Treatment Related Mortality | 3 | NA | 3 |
Hypersensitivity Reactions | |||
Any | 6 | 0 | 1 |
Grade 3/4 | 3 | 0 | 0 |
Fluid Retention | |||
Any | 3 | ND § | 23 |
Severe | 3 | 3 | |
Neurosensory | |||
Any | 23 | 14 | 29 |
Grade 3/4 | 2 | 6 | 5 |
Neuromotor | |||
Any | 16 | 8 | 10 |
Grade 3/4 | 5 | 6 | 3 |
Skin | |||
Any | 20 | 6 | 17 |
Grade 3/4 | 1 | 2 | 1 |
Gastrointestinal | |||
Nausea | |||
Any | 34 | 31 | 31 |
Grade 3/4 | 5 | 4 | 8 |
Vomiting | |||
Any | 22 | 27 | 22 |
Grade 3/4 | 3 | 2 | 6 |
Diarrhea | |||
Any | 23 | 6 | 12 |
Grade 3/4 | 3 | 0 | 4 |
Alopecia | 56 | 35 | 50 |
Asthenia | |||
Any | 53 | 57 | 54 |
Severe ¶ | 18 | 39 | 23 |
Stomatitis | |||
Any | 26 | 6 | 8 |
Grade 3/4 | 2 | 0 | 1 |
Pulmonary | |||
Any | 41 | 49 | 45 |
Grade 3/4 | 21 | 29 | 19 |
Nail Disorder | |||
Any | 11 | 0 | 2 |
Severe | 1 | 0 | 0 |
Myalgia | |||
Any | 6 | 0 | 3 |
Severe | 0 | 0 | 0 |
Arthralgia | |||
Any | 3 | 2 | 2 |
Severe | 0 | 0 | 1 |
Taste Perversion | |||
Any | 6 | 0 | 0 |
Severe | 1 | 0 | 0 |
* Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
† Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization
‡ Not Applicable;
§ Not Done
¶ COSTART term and grading system
Combination therapy with docetaxel in chemotherapy-naïve advanced unresectable or metastatic NSCLC
Table 9 presents safety data from two arms of an open label, randomized controlled trial (TAX326) that enrolled patients with unresectable stage IIIB or IV non-small cell lung cancer and no history of prior chemotherapy. Adverse reactions were described using the NCI Common Toxicity Criteria except where otherwise noted.
| Adverse Reaction | Docetaxel 75 mg/m 2 + Cisplatin 75 mg/m 2 n=406 % | Vinorelbine 25 mg/m 2 + Cisplatin 100 mg/m 2
n=396 % |
|---|---|---|
Neutropenia | ||
Any | 91 | 90 |
Grade 3/4 | 74 | 78 |
Febrile Neutropenia | 5 | 5 |
Thrombocytopenia | ||
Any | 15 | 15 |
Grade 3/4 | 3 | 4 |
Anemia | ||
Any | 89 | 94 |
Grade 3/4 | 7 | 25 |
Infection | ||
Any | 35 | 37 |
Grade 3/4 | 8 | 8 |
Fever in absence of infection | ||
Any | 33 | 29 |
Grade 3/4 | < 1 | 1 |
Hypersensitivity Reaction * | ||
Any | 12 | 4 |
Grade 3/4 | 3 | < 1 |
Fluid Retention † | ||
Any | 54 | 42 |
All severe or life-threatening events | 2 | 2 |
Pleural effusion | ||
Any | 23 | 22 |
All severe or life-threatening events | 2 | 2 |
Peripheral edema | ||
Any | 34 | 18 |
All severe or life-threatening events | ||
Weight gain | <1 | <1 |
Any | 15 | 9 |
All severe or life-threatening events | <1 | <1 |
Neurosensory | ||
Any | 47 | 42 |
Grade 3/4 | 4 | 4 |
Neuromotor | ||
Any | 19 | 17 |
Grade 3/4 | 3 | 6 |
Skin | ||
Any | 16 | 14 |
Grade 3/4 | <1 | 1 |
Nausea | ||
Any | 72 | 76 |
Grade 3/4 | 10 | 17 |
Vomiting | ||
Any | 55 | 61 |
Grade 3/4 | 8 | 16 |
Diarrhea | ||
Any | 47 | 25 |
Grade 3/4 | 7 | 3 |
Anorexia | ||
Any | 42 | 40 |
All severe or life-threatening events | 5 | 5 |
Stomatitis | ||
Any | 24 | 21 |
Grade 3/4 | 2 | 1 |
Alopecia | ||
Any | 75 | 42 |
Grade 3 | <1 | 0 |
Asthenia | ||
Any | 74 | 75 |
All severe or life-threatening events | 12 | 14 |
Nail Disorder | ||
Any | 14 | <1 |
All severe events | <1 | 0 |
Myalgia | ||
Any | 18 | 12 |
All severe events | <1 | <1 |
The second comparison in the study, vinorelbine+cisplatin versus docetaxel + carboplatin (which did not demonstrate a superior survival associated with docetaxel [see Clinical Studies (14.3)] ) demonstrated a higher incidence of thrombocytopenia, diarrhea, fluid retention, hypersensitivity reactions, skin toxicity, alopecia and nail changes on the docetaxel + carboplatin arm, while a higher incidence of anemia, neurosensory toxicity, nausea, vomiting, anorexia and asthenia was observed on the vinorelbine+cisplatin arm.
Prostate Cancer
Combination therapy with docetaxel in patients with prostate cancer
The following data are based on the experience of 332 patients, who were treated with docetaxel 75 mg/m 2 every 3 weeks in combination with prednisone 5 mg orally twice daily (see Table 10).
| Docetaxel 75 mg/m 2 every 3 weeks + prednisone 5 mg twice daily n=332 % | Mitoxantrone 12 mg/m 2 every 3 weeks + prednisone 5 mg twice daily n=335 % | |||
|---|---|---|---|---|
| Adverse Reaction | Any | Grade 3/4 | Any | Grade 3/4 |
Anemia | 67 | 5 | 58 | 2 |
Neutropenia | 41 | 32 | 48 | 22 |
Thrombocytopenia | 3 | 1 | 8 | 1 |
Febrile neutropenia | 3 | N/A | 2 | N/A |
Infection | 32 | 6 | 20 | 4 |
Epistaxis | 6 | 0 | 2 | 0 |
Allergic Reactions | 8 | 1 | 1 | 0 |
Fluid Retention * | 24 | 1 | 5 | 0 |
Weight Gain | 8 | 0 | 3 | 0 |
Peripheral Edema | 18 | 0 | 2 | 0 |
Neuropathy Sensory | 30 | 2 | 7 | 0 |
Neuropathy Motor | 7 | 2 | 3 | 1 |
Rash/Desquamation | 6 | 0 | 3 | 1 |
Alopecia | 65 | N/A | 13 | N/A |
Nail Changes | 30 | 0 | 8 | 0 |
Nausea | 41 | 3 | 36 | 2 |
Diarrhea | 32 | 2 | 10 | 1 |
Stomatitis/Pharyngitis | 20 | 1 | 8 | 0 |
Taste Disturbance | 18 | 0 | 7 | 0 |
Vomiting | 17 | 2 | 14 | 2 |
Anorexia | 17 | 1 | 14 | 0 |
Cough | 12 | 0 | 8 | 0 |
Dyspnea | 15 | 3 | 9 | 1 |
Cardiac left ventricular function | 10 | 0 | 22 | 1 |
Fatigue | 53 | 5 | 35 | 5 |
Myalgia | 15 | 0 | 13 | 1 |
Tearing | 10 | 1 | 2 | 0 |
Arthralgia | 8 | 1 | 5 | 1 |
* Related to treatment
Gastric Cancer
Combination therapy with docetaxel in gastric adenocarcinoma
Data in the following table are based on the experience of 221 patients with advanced gastric adenocarcinoma and no history of prior chemotherapy for advanced disease, who were treated with docetaxel 75 mg/m 2 in combination with cisplatin and fluorouracil (see Table 11).
| Docetaxel 75 mg/m 2 + cisplatin 75 mg/m 2 + fluorouracil 750 mg/m 2 n=221 | Cisplatin 100 mg/m 2 + fluorouracil 1000 mg/m 2 n=224 | |||
|---|---|---|---|---|
| Adverse Reaction | Any % | Grade 3/4 % | Any % | Grade 3/4 % |
| Clinically important treatment emergent adverse reactions were determined based upon frequency, severity, and clinical impact of the adverse reaction. | ||||
Anemia | 97 | 18 | 93 | 26 |
Neutropenia | 96 | 82 | 83 | 57 |
Fever in the absence of infection | 36 | 2 | 23 | 1 |
Thrombocytopenia | 26 | 8 | 39 | 14 |
Infection | 29 | 16 | 23 | 10 |
Febrile neutropenia | 16 | N/A | 5 | N/A |
Neutropenic infection | 16 | N/A | 10 | N/A |
Allergic reactions | 10 | 2 | 6 | 0 |
Fluid retention * | 15 | 0 | 4 | 0 |
Edema | 13 | 0 | 3 | 0 |
Lethargy | 63 | 21 | 58 | 18 |
Neurosensory | 38 | 8 | 25 | 3 |
Neuromotor | 9 | 3 | 8 | 3 |
Dizziness | 16 | 5 | 8 | 2 |
Alopecia | 67 | 5 | 41 | 1 |
Rash/itch | 12 | 1 | 9 | 0 |
Nail changes | 8 | 0 | 0 | 0 |
Skin desquamation | 2 | 0 | 0 | 0 |
Nausea | 73 | 16 | 76 | 19 |
Vomiting | 67 | 15 | 73 | 19 |
Anorexia | 51 | 13 | 54 | 12 |
Stomatitis | 59 | 21 | 61 | 27 |
Diarrhea | 78 | 20 | 50 | 8 |
Constipation | 25 | 2 | 34 | 3 |
Esophagitis/dysphagia/odynophagia | 16 | 2 | 14 | 5 |
Gastrointestinal pain/cramping | 11 | 2 | 7 | 3 |
Cardiac dysrhythmias | 5 | 2 | 2 | 1 |
Myocardial ischemia | 1 | 0 | 3 | 2 |
Tearing | 8 | 0 | 2 | 0 |
Altered hearing | 6 | 0 | 13 | 2 |
* Related to treatment
Head and Neck Cancer
Combination therapy with docetaxel in head and neck cancer
Table 12 summarizes the safety data obtained from patients that received induction chemotherapy with docetaxel 75 mg/m 2 in combination with cisplatin and fluorouracil followed by radiotherapy (TAX323; 174 patients) or chemoradiotherapy (TAX324; 251 patients). The treatment regimens are described in Section 14.6.
| TAX323 (n=355) | TAX324 (n=494) | |||||||
|---|---|---|---|---|---|---|---|---|
| Docetaxel arm (n=174) | Comparator arm (n=181) | Docetaxel arm (n=251) | Comparator arm (n=243) | |||||
| Adverse Reaction (by Body System) | Any % | Grade 3/4 % | Any % | Grade 3/4 % | Any % | Grade 3/4 % | Any % | Grade 3/4 % |
| Clinically important treatment emergent adverse reactions based upon frequency, severity, and clinical impact. | ||||||||
Neutropenia | 93 | 76 | 87 | 53 | 95 | 84 | 84 | 56 |
Anemia | 89 | 9 | 88 | 14 | 90 | 12 | 86 | 10 |
Thrombocytopenia | 24 | 5 | 47 | 18 | 28 | 4 | 31 | 11 |
Infection | 27 | 9 | 26 | 8 | 23 | 6 | 28 | 5 |
Febrile neutropenia * | 5 | N/A | 2 | N/A | 12 | N/A | 7 | N/A |
Neutropenic infection | 14 | N/A | 8 | N/A | 12 | N/A | 8 | N/A |
Cancer pain | 21 | 5 | 16 | 3 | 17 | 9 | 20 | 11 |
Lethargy | 41 | 3 | 38 | 3 | 61 | 5 | 56 | 10 |
Fever in the absence of infection | 32 | 1 | 37 | 0 | 30 | 4 | 28 | 3 |
Myalgia | 10 | 1 | 7 | 0 | 7 | 0 | 7 | 2 |
Weight loss | 21 | 1 | 27 | 1 | 14 | 2 | 14 | 2 |
Allergy | 6 | 0 | 3 | 0 | 2 | 0 | 0 | 0 |
Fluid retention † | 20 | 0 | 14 | 1 | 13 | 1 | 7 | 2 |
Edema only | 13 | 0 | 7 | 0 | 12 | 1 | 6 | 1 |
Weight gain only | 6 | 0 | 6 | 0 | 0 | 0 | 1 | 0 |
Dizziness | 2 | 0 | 5 | 1 | 16 | 4 | 15 | 2 |
Neurosensory | 18 | 1 | 11 | 1 | 14 | 1 | 14 | 0 |
Altered hearing | 6 | 0 | 10 | 3 | 13 | 1 | 19 | 3 |
Neuromotor | 2 | 1 | 4 | 1 | 9 | 0 | 10 | 2 |
Alopecia | 81 | 11 | 43 | 0 | 68 | 4 | 44 | 1 |
Rash/itch | 12 | 0 | 6 | 0 | 20 | 0 | 16 | 1 |
Dry skin | 6 | 0 | 2 | 0 | 5 | 0 | 3 | 0 |
Desquamation | 4 | 1 | 6 | 0 | 2 | 0 | 5 | 0 |
Nausea | 47 | 1 | 51 | 7 | 77 | 14 | 80 | 14 |
Stomatitis | 43 | 4 | 47 | 11 | 66 | 21 | 68 | 27 |
Vomiting | 26 | 1 | 39 | 5 | 56 | 8 | 63 | 10 |
Diarrhea | 33 | 3 | 24 | 4 | 48 | 7 | 40 | 3 |
Constipation | 17 | 1 | 16 | 1 | 27 | 1 | 38 | 1 |
Anorexia | 16 | 1 | 25 | 3 | 40 | 12 | 34 | 12 |
Esophagitis/dysphagia/ | 13 | 1 | 18 | 3 | 25 | 13 | 26 | 10 |
Taste, sense of smell altered | 10 | 0 | 5 | 0 | 20 | 0 | 17 | 1 |
Gastrointestinal pain/cramping | 8 | 1 | 9 | 1 | 15 | 5 | 10 | 2 |
Heartburn | 6 | 0 | 6 | 0 | 13 | 2 | 13 | 1 |
Gastrointestinal bleeding | 4 | 2 | 0 | 0 | 5 | 1 | 2 | 1 |
Cardiac dysrhythmia | 2 | 2 | 2 | 1 | 6 | 3 | 5 | 3 |
Venous ‡ | 3 | 2 | 6 | 2 | 4 | 2 | 5 | 4 |
Ischemia myocardial | 2 | 2 | 1 | 0 | 2 | 1 | 1 | 1 |
Tearing | 2 | 0 | 1 | 0 | 2 | 0 | 2 | 0 |
Conjunctivitis | 1 | 0 | 1 | 0 | 1 | 0 | 0.4 | 0 |
Body as a whole: diffuse pain, chest pain, radiation recall phenomenon.
Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction.
Gastrointestinal: abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, ischemic colitis, colitis, intestinal obstruction, ileus, neutropenic enterocolitis and dehydration as a consequence to gastrointestinal events have been reported.
Hepatic: rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, have been reported.
Neurologic: confusion, rare cases of seizures or transient loss of consciousness have been observed, sometimes appearing during the infusion of the drug.
Hearing: rare cases of ototoxicity, hearing disorders and/or hearing loss have been reported, including cases associated with other ototoxic drugs.
Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis have rarely been reported and may be associated with fatal outcome. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.
Renal: renal insufficiency and renal failure have been reported, the majority of these cases were associated with concomitant nephrotoxic drugs.
Metabolism and nutrition disorders: cases of hyponatremia have been reported.
Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4.
In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4. Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. In patients receiving treatment with Docetaxel Injection, close monitoring for toxicity and a Docetaxel Injection dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].
Pregnancy Category D. [see 'Warnings and Precautions' section]
Based on its mechanism of action and findings in animals, Docetaxel Injection can cause fetal harm when administered to a pregnant woman. If Docetaxel Injection is 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. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Docetaxel Injection.
Docetaxel Injection can cause fetal harm when administered to a pregnant woman. Studies in both rats and rabbits at doses ≥0.3 and 0.03 mg/kg/day, respectively (about 1/50 and 1/300 the daily maximum recommended human dose on a mg/m 2 basis), administered during the period of organogenesis, have shown that docetaxel is embryotoxic and fetotoxic (characterized by intrauterine mortality, increased resorption, reduced fetal weight, and fetal ossification delay). The doses indicated above also caused maternal toxicity.
It is not known whether docetaxel 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 Docetaxel Injection, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of Docetaxel Injection in pediatric patients have not been established. The alcohol content of Docetaxel Injection should be taken into account when given to pediatric patients [ see Warnings and Precautions (5.11) ].
Non-Small Cell Lung Cancer
In a study conducted in chemotherapy-naïve patients with NSCLC (TAX326), 148 patients (36%) in the docetaxel+cisplatin group were 65 years of age or greater. There were 128 patients (32%) in the vinorelbine+cisplatin group 65 years of age or greater. In the docetaxel+cisplatin group, patients < 65 years of age had a median survival of 10.3 months (95% CI: 9.1 months, 11.8 months) and patients 65 years or older had a median survival of 12.1 months (95% CI: 9.3 months, 14 months). In patients 65 years of age or greater treated with docetaxel+cisplatin, diarrhea (55%), peripheral edema (39%) and stomatitis (28%) were observed more frequently than in the vinorelbine+cisplatin group (diarrhea 24%, peripheral edema 20%, stomatitis 20%). Patients treated with docetaxel+cisplatin who were 65 years of age or greater were more likely to experience diarrhea (55%), infections (42%), peripheral edema (39%) and stomatitis (28%) compared to patients < the age of 65 administered the same treatment (43%, 31%, 31% and 21%, respectively).
When docetaxel was combined with carboplatin for the treatment of chemotherapy-naïve, advanced non-small cell lung carcinoma, patients 65 years of age or greater (28%) experienced higher frequency of infection compared to similar patients treated with docetaxel+cisplatin, and a higher frequency of diarrhea, infection and peripheral edema than elderly patients treated with vinorelbine+cisplatin.
Prostate Cancer
Of the 333 patients treated with docetaxel every three weeks plus prednisone in the prostate cancer study (TAX327), 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with docetaxel every three weeks, the following treatment emergent adverse reactions 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.
Breast Cancer
In the adjuvant breast cancer trial (TAX316), docetaxel in combination with doxorubicin and cyclophosphamide was administered to 744 patients of whom 48 (6%) were 65 years of age or greater. The number of elderly patients who received this regimen was not sufficient to determine whether there were differences in safety and efficacy between elderly and younger patients.
Gastric Cancer
Among the 221 patients treated with docetaxel in combination with cisplatin and fluorouracil in the gastric cancer study, 54 were 65 years of age or older and 2 patients were older than 75 years. In this study, the number of patients who were 65 years of age or older was insufficient to determine whether they respond differently from younger patients. However, the incidence of serious adverse reactions was higher in the elderly patients compared to younger patients. The incidence of the following adverse reactions (all grades, regardless of relationship): lethargy, stomatitis, diarrhea, dizziness, edema, febrile neutropenia/neutropenic infection occurred at rates ≥ 10% higher in patients who were 65 years of age or older compared to younger patients. Elderly patients treated with TCF should be closely monitored.
Head and Neck Cancer
Among the 174 and 251 patients who received the induction treatment with docetaxel in combination with cisplatin and fluorouracil (TPF) for SCCHN in the TAX323 and TAX324 studies, 18 (10%) and 32 (13%) of the patients were 65 years of age or older, respectively.
These clinical studies of docetaxel in combination with cisplatin and fluorouracil in patients with SCCHN did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience with this treatment regimen has not identified differences in responses between elderly and younger patients.
Patients with bilirubin >ULN should not receive Docetaxel Injection. Also, patients with AST and/or ALT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN should not receive Docetaxel Injection. [see Boxed Warning, Warnings and Precautions (5.2), Clinical Pharmacology (12.3)].
The alcohol content of Docetaxel Injection should be taken into account when given to patients with hepatic impairment [ see Warnings and Precautions (5.11) ].
There is no known antidote for Docetaxel Injection overdosage. In case of overdosage, the patient should be kept in a specialized unit where vital functions can be closely monitored. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.
In two reports of overdose, one patient received 150 mg/m 2 and the other received 200 mg/m 2 as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident.
In mice, lethality was observed following single intravenous doses that were ≥154 mg/kg (about 4.5 times the human dose of 100 mg/m 2 on a mg/m 2 basis); neurotoxicity associated with paralysis, non-extension of hind limbs, and myelin degeneration was observed in mice at 48 mg/kg (about 1.5 times the human dose of 100 mg/m 2 basis). In male and female rats, lethality was observed at a dose of 20 mg/kg (comparable to the human dose of 100 mg/m 2 on a mg/m 2 basis) and was associated with abnormal mitosis and necrosis of multiple organs.
Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical name for docetaxel is (2R,3S)-N-carboxy-3-phenylisoserine,N- tert-butyl ester, 13-ester with 5β-20-epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate. Docetaxel has the following structural formula:
Docetaxel is a white to off-white powder with an empirical formula of C 43H 53NO 14 and a molecular weight of 807.88. It is highly lipophilic and practically insoluble in water.
Two-vial formulation (Injection with Diluent)
Docetaxel Injection USP is a clear yellow to brownish-yellow viscous solution. Docetaxel Injection USP is sterile, non-pyrogenic, and is available in single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL) docetaxel anhydrous USP. Each mL contains 40 mg docetaxel anhydrous USP, 60 mg dehydrated alcohol and 1040 mg polysorbate 80. Citric acid (anhydrous) may be used to adjust the pH.
Docetaxel Injection USP requires dilution with Diluent prior to addition to the infusion bag. A sterile, non-pyrogenic, single-dose diluent is supplied for that purpose. The diluent for Docetaxel Injection USP contains 13% polyethylene glycol 400 in water for injection, and is supplied in vials.
One-vial formulation (Injection)
Docetaxel Injection USP is a sterile, non-pyrogenic, pale yellow to brownish-yellow solution at 20 mg/mL concentration.
Each mL contains 20 mg docetaxel anhydrous USP, 4 mg anhydrous citric acid, 520 mg polysorbate 80 and 395 mg dehydrated alcohol solution.
Docetaxel Injection USP is available in single dose and multiple dose vials containing 20 mg (1 mL), 80 mg (4 mL) or 160 mg (8 mL) docetaxel anhydrous USP.
Docetaxel Injection USP requires NO prior dilution with a diluent and is ready to add to the infusion solution.
Absorption: The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20 mg/m 2 to 115 mg/m 2 in phase 1 studies. The area under the curve (AUC) was dose proportional following doses of 70 mg/m 2 to 115 mg/m 2 with infusion times of 1 to 2 hours. Docetaxel's pharmacokinetic profile is 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 hr, respectively. Mean total body clearance was 21 L/h/m 2
Distribution: The initial rapid decline represents distribution to the peripheral compartments and the late (terminal) phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment. Mean steady state volume of distribution was 113 L. In vitro studies showed that docetaxel is about 94% protein bound, mainly to α 1 -acid glycoprotein, albumin, and lipoproteins. In three cancer patients, the in vitro binding to plasma proteins was found to be approximately 97%. Dexamethasone does not affect the protein binding of docetaxel.
Metabolism: In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme, and its metabolism may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4 [see Drug Interactions (7)].
Elimination: A study of 14C-docetaxel was conducted in three cancer patients. Docetaxel was eliminated in both the urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. About 80% of the radioactivity recovered in feces is excreted during the first 48 hours as 1 major and 3 minor metabolites with very small amounts (< 8%) of unchanged drug.
Effect of Age: A population pharmacokinetic analysis was carried out after docetaxel treatment of 535 patients dosed at 100 mg/m 2. Pharmacokinetic parameters estimated by this analysis were very close to those estimated from phase 1 studies. The pharmacokinetics of docetaxel were not influenced by age.
Effect of Gender: The population pharmacokinetics analysis described above also indicated that gender did not influence the pharmacokinetics of docetaxel.
Effect of Race: Mean total body clearance for Japanese patients dosed at the range of 10 mg/m 2 to 90 mg/m 2 was similar to that of European/American populations dosed at 100 mg/m 2, suggesting no significant difference in the elimination of docetaxel in the two populations.
Effect of Ketoconazole: The effect of ketoconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics of docetaxel was investigated in 7 cancer patients. Patients were randomized to receive either docetaxel (100 mg/m 2 intravenous) alone or docetaxel (10 mg/m 2 intravenous) in combination with ketoconazole (200 mg orally once daily for 3 days) in a crossover design with a 3-week washout period. The results of this study indicated that the mean dose-normalized AUC of docetaxel was increased 2.2-fold and its clearance was reduced by 49% when docetaxel was co-administration with ketoconazole [see Dosage and Administration (2.7) and Drug-Drug Interactions (7)]
Effect of Combination Therapies:
Carcinogenicity studies with docetaxel have not been performed.
Docetaxel was clastogenic in the in vitro chromosome aberration test in CHO-K 1 cells and in the in vivo micronucleus test in mice administered doses of 0.39 to 1.56 mg/kg (about 1/60 th to 1/15 th the recommended human dose on a mg/m 2 basis). Docetaxel was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assays.
Docetaxel did not reduce fertility in rats when administered in multiple intravenous doses of up to 0.3 mg/kg (about 1/50 th the recommended human dose on a mg/m 2 basis), but decreased testicular weights were reported. This correlates with findings of a 10-cycle toxicity study (dosing once every 21 days for 6 months) in rats and dogs in which testicular atrophy or degeneration was observed at intravenous doses of 5 mg/kg in rats and 0.375 mg/kg in dogs (about 1/3 rd and 1/15 th the recommended human dose on a mg/m 2 basis, respectively). An increased frequency of dosing in rats produced similar effects at lower dose levels.
The efficacy and safety of another formulation of docetaxel have been evaluated in locally advanced or metastatic breast cancer after failure of previous chemotherapy (alkylating agent-containing regimens or anthracycline-containing regimens).
Randomized Trials
In one randomized trial, patients with a history of prior treatment with an anthracycline containing regimen were assigned to treatment with docetaxel (100 mg/m 2 every 3 weeks) or the combination of mitomycin (12 mg/m 2 every 6 weeks) and vinblastine (6 mg/m 2 every 3 weeks). Two hundred three patients were randomized to docetaxel and 189 to the comparator arm. Most patients had received prior chemotherapy for metastatic disease; only 27 patients on the docetaxel arm and 33 patients on the comparator arm entered the study following relapse after adjuvant therapy. Three-quarters of patients had measurable, visceral metastases. The primary endpoint was time to progression. The following table summarizes the study results (See Table 13).
| Efficacy Parameter | Docetaxel (n=203) | Mitomycin/Vinblastine (n=189) | p-value |
|---|---|---|---|
Median Survival | 11.4 months | 8.7 months | |
Risk Ratio *, Mortality | 0.73 | p=0.01 | |
95% CI (Risk Ratio) | 0.58 to 0.93 | ||
Median Time to Progression | 4.3 months | 2.5 months | |
Risk Ratio , Progression | 0.75 | p=0.01 | |
95% CI (Risk Ratio) | 0.61 to 0.94 | ||
Overall Response Rate | 28.1% | 9.5% | p<0.0001 |
Complete Response Rate | 3.4% | 1.6% | Chi Square |
* For the risk ratio, a value < 1.00 favors docetaxel.
In a second randomized trial, patients previously treated with an alkylating-containing regimen were assigned to treatment with docetaxel (100 mg/m 2) or doxorubicin (75 mg/m 2) every 3 weeks. One hundred sixty-one patients were randomized to docetaxel and 165 patients to doxorubicin. Approximately one-half of patients had received prior chemotherapy for metastatic disease, and one-half entered the study following relapse after adjuvant therapy. Three-quarters of patients had measurable, visceral metastases. The primary endpoint was time to progression. The study results are summarized below (See Table 14).
| Efficacy Parameter | Docetaxel (n=161) | Doxorubicin (n=165) | p-value |
|---|---|---|---|
Median Survival | 14.7 months | 14.3 months | |
Risk Ratio *, Mortality | 0.89 | p=0.39 | |
95% CI (Risk Ratio) | 0.68 to 1.16 | ||
Median Time to Progression | 6.5 months | 5.3 months | |
Risk Ratio , Progression | 0.93 | p=0.45 | |
95% CI (Risk Ratio) | 0.71 to 1.16 | ||
Overall Response Rate | 45.3% | 29.7% | p=0.004 |
Complete Response Rate | 6.8% | 4.2% | Chi Square |
* For the risk ratio, a value < 1.00 favors docetaxel.
In another multicenter open-label, randomized trial (TAX313), in the treatment of patients with advanced breast cancer who progressed or relapsed after one prior chemotherapy regimen, 527 patients were randomized to receive docetaxel monotherapy 60 mg/m 2 (n=151), 75 mg/m 2 (n=188) or 100 mg/m 2 (n=188). In this trial, 94% of patients had metastatic disease and 79% had received prior anthracycline therapy. Response rate was the primary endpoint. Response rates increased with docetaxel dose: 19.9% for the 60 mg/m 2 group compared to 22.3% for the 75 mg/m 2 and 29.8% for the 100 mg/m 2 group; pair-wise comparison between the 60 mg/m 2 and 100 mg/m 2 groups was statistically significant (p=0.037).
Single Arm Studies
Docetaxel at a dose of 100 mg/m 2 was studied in six single arm studies involving a total of 309 patients with metastatic breast cancer in whom previous chemotherapy had failed. Among these, 190 patients had anthracycline-resistant breast cancer, defined as progression during an anthracycline-containing chemotherapy regimen for metastatic disease, or relapse during an anthracycline-containing adjuvant regimen. In anthracycline-resistant patients, the overall response rate was 37.9% (72/190; 95% C.I.: 31.0 to 44.8) and the complete response rate was 2.1%.
Docetaxel was also studied in three single arm Japanese studies at a dose of 60 mg/m 2, in 174 patients who had received prior chemotherapy for locally advanced or metastatic breast cancer. Among 26 patients whose best response to an anthracycline had been progression, the response rate was 34.6% (95% C.I.: 17.2 to 55.7), similar to the response rate in single arm studies of 100 mg/m 2.
A multicenter, open-label, randomized trial (TAX316) evaluated the efficacy and safety of another formulation of docetaxel for the adjuvant treatment of patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease. After stratification according to the number of positive lymph nodes (1 to 3, 4+), 1491 patients were randomized to receive either docetaxel 75 mg/m 2 administered 1-hour after doxorubicin 50 mg/m 2 and cyclophosphamide 500 mg/m 2 (TAC arm), or doxorubicin 50 mg/m 2 followed by fluorouracil 500 mg/m 2 and cyclosphosphamide 500 mg/m 2 (FAC arm). Both regimens were administered every 3 weeks for 6 cycles.
Docetaxel was administered as a 1-hour infusion; all other drugs were given as intravenous bolus on day 1. In both arms, after the last cycle of chemotherapy, patients with positive estrogen and/or progesterone receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed according to guidelines in place at participating institutions and was given to 69% of patients who received TAC and 72% of patients who received FAC.
Results from a second interim analysis (median follow-up 55 months) are as follows: In study TAX316, the docetaxel-containing combination regimen TAC showed significantly longer disease-free survival (DFS) than FAC (hazard ratio=0.74; 2-sided 95% CI=0.60, 0.92, stratified log rank p=0.0047). The primary endpoint, disease-free survival, included local and distant recurrences, contralateral breast cancer and deaths from any cause. The overall reduction in risk of relapse was 25.7% for TAC-treated patients. (See Figure 1).
Figure 1 - TAX316 Disease Free Survival K-M curve
Figure 2 - TAX316 Overall Survival K-M curve
The following table describes the results of subgroup analyses for DFS and OS (See Table 15).
| Disease Free Survival | Overall Survival | ||||
|---|---|---|---|---|---|
| Patient subset | Number of patients | Hazard ratio * | 95% CI | Hazard ratio | 95% CI |
No. of positive nodes | |||||
Overall | 744 | 0.74 | (0.60, 0.92) | 0.69 | (0.53, 0.90) |
1 to 3 | 467 | 0.64 | (0.47, 0.87) | 0.45 | (0.29, 0.70) |
4+ | 277 | 0.84 | (0.63, 1.12) | 0.93 | (0.66, 1.32) |
Receptor status | |||||
Positive | 566 | 0.76 | (0.59, 0.98) | 0.69 | (0.48, 0.99) |
Negative | 178 | 0.68 | (0.48, 0.97) | 0.66 | (0.44, 0.98) |
* a hazard ratio of < 1 indicates that TAC is associated with a longer disease free survival or overall survival compared to FAC.
Monotherapy with docetaxel for NSCLC Previously Treated with Platinum Based Chemotherapy
Two randomized, controlled trials established that a docetaxel dose of 75 mg/m 2 was tolerable and yielded a favorable outcome in patients previously treated with platinum-based chemotherapy (see below). Docetaxel at a dose of 100 mg/m 2, however, was associated with unacceptable hematologic toxicity, infections, and treatment-related mortality and this dose should not be used [see Boxed Warning, Dosage and Administration (2.7), Warnings and Precautions (5.3)].
One trial (TAX317), randomized patients with locally advanced or metastatic non-small cell lung cancer, a history of prior platinum-based chemotherapy, no history of taxane exposure, and an ECOG performance status ≤2 to docetaxel or best supportive care. The primary endpoint of the study was survival. Patients were initially randomized to docetaxel 100 mg/m 2 or best supportive care, but early toxic deaths at this dose led to a dose reduction to docetaxel 75 mg/m 2. A total of 104 patients were randomized in this amended study to either docetaxel 75 mg/m 2 or best supportive care.
In a second randomized trial (TAX320), 373 patients with locally advanced or metastatic non small cell lung cancer, a history of prior platinum-based chemotherapy, and an ECOG performance status ≤2 were randomized to docetaxel 75 mg/m 2, docetaxel 100 mg/m 2 and a treatment in which the investigator chose either vinorelbine 30 mg/m 2 days 1, 8, and 15 repeated every 3 weeks or ifosfamide 2 g/m 2 days 1 to 3 repeated every 3 weeks. Forty percent of the patients in this study had a history of prior paclitaxel exposure. The primary endpoint was survival in both trials. The efficacy data for the docetaxel 75 mg/m 2 arm and the comparator arms are summarized in Table 16 and Figures 3 and 4 showing the survival curves for the two studies.
| TAX317 | TAX320 | |||
|---|---|---|---|---|
| Docetaxel 75 mg/m 2 n=55 | Best Supportive Care n=49 | Docetaxel 75 mg/m 2 n=125 | Control (V/I *) n=123 | |
Overall Survival | ||||
Log-rank Test | p=0.01 | p=0.13 | ||
Risk Ratio †, Mortality | ||||
(Docetaxel: Control) | 0.56 | 0.82 | ||
95% CI (Risk Ratio) | (0.35, 0.88) | (0.63, 1.06) | ||
Median Survival | 7.5 months ‡ | 4.6 months | 5.7 months | 5.6 months |
95% CI | (5.5, 12.8) | (3.7, 6.1) | (5.1, 7.1) | (4.4, 7.9) |
% 1-year Survival | 37% § | 12% | 30% | 20% |
95% CI | (24, 50) | (2, 23) | (22, 39) | (13, 27) |
Time to Progression | 12.3 weeks | 7.0 weeks | 8.3 weeks | 7.6 weeks |
95% CI | (9.0, 18.3) | (6.0, 9.3) | (7.0, 11.7) | (6.7, 10.1) |
Response Rate | 5.5% | Not Applicable | 5.7% | 0.8% |
95% CI | (1.1, 15.1) | (2.3, 11.3) | (0.0, 4.5) | |
* Vinorelbine/Ifosfamide
† a value < 1.00 favors docetaxel
‡ p≤0.05
§ uncorrected for multiple comparisons
Only one of the two trials (TAX317) showed a clear effect on survival, the primary endpoint; that trial also showed an increased rate of survival to one year. In the second study (TAX320) the rate of survival at one year favored docetaxel 75 mg/m 2.
Figure 3 - TAX317 Survival K-M Curves - Docetaxel 75 mg/m 2 vs. Best Supportive Care
Figure 4 - TAX320 Survival K-M Curves - Docetaxel 75 mg/m 2 vs. Vinorelbine or Ifosfamide Control
Patients treated with docetaxel at a dose of 75 mg/m 2 experienced no deterioration in performance status and body weight relative to the comparator arms used in these trials.
Combination Therapy with docetaxel for Chemotherapy-Naïve NSCLC
In a randomized controlled trial (TAX326), 1218 patients with unresectable stage IIIB or IV NSCLC and no prior chemotherapy were randomized to receive one of three treatments: docetaxel 75 mg/m 2 as a 1 hour infusion immediately followed by cisplatin 75 mg/m 2 over 30 to 60 minutes every 3 weeks; vinorelbine 25 mg/m 2 administered over 6 to 10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m 2 administered on day 1 of cycles repeated every 4 weeks; or a combination of docetaxel and carboplatin.
The primary efficacy endpoint was overall survival. Treatment with docetaxel+cisplatin did not result in a statistically significantly superior survival compared to vinorelbine+cisplatin (see table below). The 95% confidence interval of the hazard ratio (adjusted for interim analysis and multiple comparisons) shows that the addition of docetaxel to cisplatin results in an outcome ranging from a 6% inferior to a 26% superior survival compared to the addition of vinorelbine to cisplatin. The results of a further statistical analysis showed that at least (the lower bound of the 95% confidence interval) 62% of the known survival effect of vinorelbine when added to cisplatin (about a 2-month increase in median survival; Wozniak et al. JCO, 1998) was maintained. The efficacy data for the docetaxel+cisplatin arm and the comparator arm are summarized in Table 17.
| Comparison | Docetaxel + Cisplatin n=408 | Vinorelbine + Cisplatin n=405 |
|---|---|---|
Kaplan-Meier Estimate of Median Survival | 10.9 months | 10.0 months |
p-value * | 0.122 | |
Estimated Hazard Ratio † | 0.88 | |
Adjusted 95% CI ‡ | (0.74, 1.06) | |
* From the superiority test (stratified log rank) comparing docetaxel + cisplatin to vinorelbine+cisplatin
† Hazard ratio of docetaxel + cisplatin vs. vinorelbine + cisplatin. A hazard ratio of < 1 indicates that docetaxel + cisplatin is associated with a longer survival.
‡ Adjusted for interim analysis and multiple comparisons.
The second comparison in the same three-arm study, vinorelbine+cisplatin versus docetaxel+carboplatin, did not demonstrate superior survival associated with the docetaxel arm (Kaplan-Meier estimate of median survival was 9.1 months for docetaxel +carboplatin compared to 10.0 months on the vinorelbine+cisplatin arm) and the docetaxel+carboplatin arm did not demonstrate preservation of at least 50% of the survival effect of vinorelbine added to cisplatin. Secondary endpoints evaluated in the trial included objective response and time to progression. There was no statistically significant difference between docetaxel+cisplatin and vinorelbine+cisplatin with respect to objective response and time to progression (see Table 18).
| Endpoint | Docetaxel + Cisplatin | Vinorelbine + Cisplatin | p-value |
|---|---|---|---|
Objective Response Rate | 31.6% | 24.4% | Not Significant |
(95% CI) * | (26.5%, 36.8%) | (19.8%, 29.2%) | |
Median Time to Progression † | 21.4 weeks | 22.1 weeks | Not Significant |
(95% CI) |
The safety and efficacy of another formulation of docetaxel in combination with prednisone in patients with androgen independent (hormone refractory) metastatic prostate cancer were evaluated in a randomized multicenter active control trial. A total of 1006 patients with Karnofsky Performance Status (KPS) ≥60 were randomized to the following treatment groups:
All 3 regimens were administered in combination with prednisone 5 mg twice daily, continuously.
In the docetaxel every three week arm, a statistically significant overall survival advantage was demonstrated compared to mitoxantrone. In the docetaxel weekly arm, no overall survival advantage was demonstrated compared to the mitoxantrone control arm. Efficacy results for the docetaxel every 3 week arm versus the control arm are summarized in Table 19 and Figure 5.
| Docetaxel + Prednisone every 3 weeks | Mitoxantrone + Prednisone every 3 weeks | |
|---|---|---|
Number of patients | 335 | 337 |
Median survival (months) | 18.9 | 16.5 |
95% CI | (17.0 to 21.2) | (14.4 to 18.6) |
Hazard ratio | 0.761 | -- |
95% CI | (0.619 to 0.936) | -- |
p-value * | 0.0094 | -- |
* Stratified log rank test. Threshold for statistical significance = 0.0175 because of 3 arms.
Figure 5 - TAX327 Survival K-M Curves
A multicenter, open-label, randomized trial was conducted to evaluate the safety and efficacy of another formulation of docetaxel for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. A total of 445 patients with KPS >70 were treated with either docetaxel (T) (75 mg/m 2 on day 1) in combination with cisplatin (C) (75 mg/m 2 on day 1) and fluorouracil (F) (750 mg/m 2 per day for 5 days) or cisplatin (100 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 per day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF arm. The demographic characteristics were balanced between the two treatment arms. The median age was 55 years, 71% were male, 71% were Caucasian, 24% were 65 years of age or older, 19% had a prior curative surgery and 12% had palliative surgery. The median number of cycles administered per patient was 6 (with a range of 1 to 16) for the TCF arm compared to 4 (with a range of 1 to 12) for the CF arm. Time to progression (TTP) was the primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization. The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95% CI: 1.19 to 1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. Approximately 75% of patients had died at the time of this analysis. Overall survival was significantly longer (p=0.0201) in the TCF arm with a HR of 1.29 (95% CI: 1.04 to 1.61). Efficacy results are summarized in Table 20 and Figures 6 and 7.
| Endpoint | TCF n=221 | CF n=224 |
|---|---|---|
Median TTP (months) | 5.6 | 3.7 |
(95%CI) | (4.86 to 5.91) | (3.45 to 4.47) |
Hazard ratio * | 0.68 | |
(95%CI) | (0.55 to 0.84) | |
†p-value | 0.0004 | |
Median survival (months) | 9.2 | 8.6 |
(95%CI) | (8.38 to 10.58) | (7.16 to 9.46) |
Hazard ratio | 0.77 | |
(95%CI) | (0.62 to 0.96) | |
p-value | 0.0201 | |
Overall Response Rate (CR+PR) (%) | 36.7 | 25.4 |
p-value | 0.0106 | |
Subgroup analyses were consistent with the overall results across age, gender and race.
Figure 6 - Gastric Cancer Study (TAX325) Time to Progression K-M Curve
Figure 7 - Gastric Cancer Study (TAX325) Survival K-M Curve
Induction chemotherapy followed by radiotherapy (TAX323)
The safety and efficacy of another formulation of docetaxel in the induction treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a multicenter, open-label, randomized trial (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, and WHO performance status 0 or 1, were randomized to one of two treatment arms. Patients on the docetaxel arm received docetaxel (T) 75 mg/m 2 followed by cisplatin (P) 75 mg/m 2 on Day 1, followed by fluorouracil (F) 750 mg/m 2 per day as a continuous infusion on Days 1 to 5. The cycles were repeated every three weeks for 4 cycles. Patients whose disease did not progress received radiotherapy (RT) according to institutional guidelines (TPF/RT). Patients on the comparator arm received cisplatin (P) 100 mg/m 2 on Day 1, followed by fluorouracil (F) 1000 mg/m 2/day as a continuous infusion on Days 1 to 5. The cycles were repeated every three weeks for 4 cycles. Patients whose disease did not progress received RT according to institutional guidelines (PF/RT). At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to institutional guidelines. Locoregional therapy with radiation was delivered either with a conventional fraction regimen (1.8 Gy to 2.0 Gy once a day, 5 days per week for a total dose of 66 to 70 Gy) or with an accelerated/hyperfractionated regimen (twice a day, with a minimum interfraction interval of 6 hours, 5 days per week, for a total dose of 70 to 74 Gy, respectively). Surgical resection was allowed following chemotherapy, before or after radiotherapy.
| ENDPOINT | Docetaxel+ Cisplatin+ Fluorouracil n=177 | Cisplatin+ Fluorouracil n=181 |
|---|---|---|
| A Hazard ratio of < 1 favors Docetaxel+Cisplatin+Fluorouracil | ||
Median progression free survival (months) | 11.4 | 8.3 |
Adjusted Hazard ratio | 0.71 | |
Median survival (months) | 18.6 | 14.2 |
Hazard ratio | 0.71 | |
Best overall response (CR + PR) to | 67.8 | 53.6 |
‡p-value | 0.006 | |
Best overall response (CR + PR) to study | 72.3 | 58.6 |
p-value | 0.006 | |
* Stratified log-rank test based on primary tumor site
† Stratified log-rank test, not adjusted for multiple comparisons
‡ Chi square test, not adjusted for multiple comparisons
Figure 8 - TAX323 Progression-Free Survival K-M Curve
Figure 9 - TAX323 Overall Survival K-M Curve
Induction chemotherapy followed by chemoradiotherapy (TAX324)
The safety and efficacy of another formulation of docetaxel in the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN was evaluated in a randomized, multicenter open-label trial (TAX324). In this study, 501 patients, with locally advanced SCCHN, and a WHO performance status of 0 or 1, were randomized to one of two treatment arms. Patients on the docetaxel arm received docetaxel (T) 75 mg/m 2 by intravenous infusion on day 1 followed by cisplatin (P) 100 mg/m 2 administered as a 30-minute to three-hour intravenous infusion, followed by the continuous intravenous infusion of fluorouracil (F) 1000 mg/m 2/day from day 1 to day 4. The cycles were repeated every 3 weeks for 3 cycles. Patients on the comparator arm received cisplatin (P) 100 mg/m 2 as a 30-minute to three-hour intravenous infusion on day 1 followed by the continuous intravenous infusion of fluorouracil (F) 1000 mg/m 2/day from day 1 to day 5. The cycles were repeated every 3 weeks for 3 cycles.
The primary efficacy endpoint, overall survival (OS), was significantly longer (log-rank test, p=0.0058) with the docetaxel-containing regimen compared to PF [median OS: 70.6 versus 30.1 months respectively, hazard ratio (HR)=0.70, 95% confidence interval (CI)= 0.54 to 0.90]. Overall survival results are presented in Table 22 and Figure 10.
| ENDPOINT | Docetaxel + Cisplatin+ Fluorouracil n=255 | Cisplatin+ Fluorouracil n=246 |
|---|---|---|
| A Hazard ratio of < 1 favors docetaxel + cisplatin + fluorouracil | ||
| NE - not estimable | ||
Median overall survival (months) | 70.6 | 30.1 |
Hazard ratio: | 0.70 | |
* un-adjusted log-rank test
Figure 10 - TAX324 Overall Survival K-M Curve
www.osha.gov/SLTC/hazardousdrugs/index.htmlOne-vial formulation (Injection)
Docetaxel Injection is supplied in single dose and multiple dose vials as a sterile, pyrogen-free, non-aqueous solution.
Docetaxel Injection 80 mg/4 mL: The vial is in one carton. NDC 63739-971-17
Docetaxel Injection 20 mg/mL: The vial is in one carton. NDC 63739-932-11
Two-vial formulation (Injection with Diluent)
One-vial formulation (Injection)
After initial puncture, Docetaxel Injection multiple dose vials are stable for 28 days when stored at room temperature, with protection from light.
Follow procedures for proper handling and disposal of anticancer drugs. 1
See FDA-Approved Patient Labeling
Manufactured by:
Intas Pharmaceuticals Limited,
Ahmedabad-380 009, India.
Distributed by:
McKesson Packaging Services,
A business unit of McKesson Corporation.
7101 Weddington Rd, Concord, NC 28027
Toll Free: 1-888-243-4363
10 10580 2 665816
Revised July 2016
INP058
| This Patient Information has been approved by the U.S. Food and Drug Administration. | |
| Revised: July 2016 | |
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Read this Patient Information before you receive your first treatment with Docetaxel Injection and each time before you are treated. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. | |
What is the most important information I should know about Docetaxel Injection?
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Who should not receive Docetaxel Injection?
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How will I receive Docetaxel Injection?
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What are the possible side effects of Docetaxel Injection?
The most common side effects of Docetaxel Injection include: | |
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What are the ingredients in Docetaxel Injection? Two-vial formulation (Injection with Diluent) Active ingredient: docetaxel anhydrous USP Inactive ingredients: dehydrated alcohol, polysorbate 80, anhydrous citric acid and polyethylene glycol 400 One-vial formulation (Injection) Active ingredient: docetaxel anhydrous USP Inactive ingredients: anhydrous citric acid, polysorbate 80 and dehydrated alcohol | |
Every three-week injection of Docetaxel Injection for breast, non-small cell lung and stomach, and head and neck cancers Take your oral corticosteroid medicine as your doctor tells you. Oral corticosteroid dosing: Day 1 Date:________ Time:_____ AM______ PM Day 2 Date:________ Time:_____ AM______ PM (Docetaxel Injection Treatment Day) Day 3 Date:________ Time:_____ AM______ PM |
Every three-week injection of Docetaxel Injection for prostate cancer Take your oral corticosteroid medicine as your doctor tells you. Oral corticosteroid dosing: Date:________ Time:_____ Date:________ Time:_____ (Docetaxel Injection Treatment Day) Time:_____ |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 63739-971-17 | ML - Milliliter | 63739-971 | 552dbb75-9fc3-4986-b023-7442c6ee8c80 | 1 | 2015-03-03 |
| 63739-932-11 | ML - Milliliter | 63739-932 | aa365ea7-887b-428f-b8f0-e869d813622c | 1 | 2015-03-03 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| DOCETAXEL ANHYDROUS | ACTIVE INGREDIENT | 699121PHCA | 5 | |
| DOCETAXEL ANHYDROUS | ACTIVE MOIETY | 699121PHCA | 5 | |
| ALCOHOL | INACTIVE INGREDIENT | 3K9958V90M | 5 | |
| ANHYDROUS CITRIC ACID | INACTIVE INGREDIENT | XF417D3PSL | 5 | |
| POLYSORBATE 80 | INACTIVE INGREDIENT | 6OZP39ZG8H | 5 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 63739-971 | 63739-971-17 |
| 63739-932 | 63739-932-11 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| ANHYDROUS CITRIC ACID | XF417D3PSL | IACT |
| POLYSORBATE 80 | 6OZP39ZG8H | IACT |
| ALCOHOL | 3K9958V90M | IACT |
| DOCETAXEL ANHYDROUS | 699121PHCA | ACTIB |
| ANHYDROUS CITRIC ACID | XF417D3PSL | IACT |
| POLYSORBATE 80 | 6OZP39ZG8H | IACT |
| ALCOHOL | 3K9958V90M | IACT |
| DOCETAXEL ANHYDROUS | 699121PHCA | ACTIB |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | SPRAY, METERED / NASAL | 0.1 mg/1ml | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SUSPENSION/ DROPS / ORAL | 15 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SUSPENSION, EXTENDED RELEASE / ORAL | 62 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SOLUTION/ DROPS / AURICULAR (OTIC) | 1 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | SUSPENSION / RESPIRATORY (INHALATION) | 1 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION / INTRALESIONAL | 4 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION / INTRA-ARTICULAR | 4 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | LIQUID / INTRAVENOUS | 720 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | CONCENTRATE / BUCCAL | 679 mg/1ml | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | PASTE / DENTAL | 1.8 %w/w | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SOLUTION / DENTAL | 12.8 %w/w | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | TABLET / ORAL | 233 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | GRANULE, FOR SUSPENSION / ORAL | 240 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SOLUTION / TOPICAL | 2445 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | INJECTION / INFILTRATION | 0.02 %w/v | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | CONCENTRATE / ORAL | 84 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | INJECTION, SOLUTION / INTRAMUSCULAR | 1000 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | GEL / TOPICAL | 12 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | POWDER / ORAL | 66 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | AEROSOL, METERED / NASAL | 70 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, POWDER, FOR SUSPENSION / INTRA-ARTICULAR | 5 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SOLUTION, CONCENTRATE / ORAL | 150.68 mg/1ml | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, SOLUTION, CONCENTRATE / INTRAVENOUS | 4739 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | GEL, METERED / TRANSDERMAL | 3675 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | TABLET, COATED / ORAL | 18 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | FILM, SOLUBLE / ORAL | 7 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | LOTION / TOPICAL | 211 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SPRAY, METERED / SUBLINGUAL | 29 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | TABLET, ORALLY DISINTEGRATING, DELAYED RELEASE / ORAL | 48 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION / INTRASYNOVIAL | 0.2 %w/v | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | TABLET, FILM COATED, EXTENDED RELEASE / ORAL | 8 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | FILM, SOLUBLE / BUCCAL | 2 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | INJECTION, SOLUTION / INTRAVENOUS | 6405 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | TABLET, DELAYED RELEASE / ORAL | 4 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | SOLUTION / ORAL | 907 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | SUSPENSION/ DROPS / OPHTHALMIC | 1 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SOLUTION, CONCENTRATE / INTRAVENOUS | 4000 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | LOZENGE / TRANSMUCOSAL | 44 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | ELIXIR / ORAL | 13675 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SYRUP / ORAL | 21000 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, SUSPENSION / INTRAVITREAL | 0.02 %w/v | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | INJECTION, SOLUTION / SUBCUTANEOUS | 6.1 %v/v | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, POWDER, FOR SUSPENSION / INTRAMUSCULAR | 4 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | CREAM / TOPICAL | 1 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | CLOTH / TOPICAL | 4.2 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SOLUTION, CONCENTRATE / INTRAVENOUS | 60 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAMUSCULAR | 1 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | GEL / TRANSDERMAL | 7360 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | INJECTION / INTRAVENOUS | 1152 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | LIQUID / INTRAVENOUS | 18 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SOLUTION / TRANSDERMAL | 49.37 %w/v | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SPRAY / TOPICAL | 0.01 %w/w | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | TABLET / SUBLINGUAL | 36 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | INJECTION, SUSPENSION / SUBCUTANEOUS | 0.3 %w/v | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | SWAB / TOPICAL | 2250 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | SOLUTION / RESPIRATORY (INHALATION) | 5 mg | ||
| ANHYDROUS CITRIC ACID | ANHYDROUS CITRIC ACID | XF417D3PSL | TABLET, EFFERVESCENT / ORAL | 840 mg | ||
| POLYSORBATE 80 | POLYSORBATE 80 | 6OZP39ZG8H | SUSPENSION/ DROPS / ORAL | 23 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | GEL / TOPICAL | 9971 mg | ||
| ALCOHOL | ALCOHOL | 3K9958V90M | LIQUID / ORAL | 3563 mg |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N201195-001 | DOCETAXEL | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | |
| N201195-002 | DOCETAXEL | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | |
| N201195-003 | DOCETAXEL | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 |
| N201195-004 | DOCETAXEL | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 |
| N201195-005 | DOCETAXEL | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 |
| Application-product | TE code |
|---|---|
| N201195-003 | AP |
| N201195-004 | AP |
| N201195-005 | AP |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-001 | DOCETAXEL | 20MG/0.5ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-002 | DOCETAXEL | 80MG/2ML (40MG/ML) | INJECTABLE / INJECTION | RLD | 2011-06-08 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-003 | DOCETAXEL | 20MG/ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-004 | DOCETAXEL | 80MG/4ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD | 2012-04-20 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-005 | DOCETAXEL | 160MG/8ML (20MG/ML) | INJECTABLE / INJECTION | AP | RLD, RS | 2012-04-20 | 03ed91905a0d… |
| Captured | Edition | Application-product | TE code | Order | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N201195-003 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N201195-004 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N201195-005 | AP | 1 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-003 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-004 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N201195-005 | AP | 1 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-003 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-004 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N201195-005 | AP | 1 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-003 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-004 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N201195-005 | AP | 1 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-003 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-004 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | N201195-005 | AP | 1 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-003 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-004 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N201195-005 | AP | 1 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-003 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-004 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N201195-005 | AP | 1 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-003 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-004 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N201195-005 | AP | 1 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N201195-003 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N201195-004 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N201195-005 | AP | 1 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N201195-003 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N201195-004 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N201195-005 | AP | 1 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N201195-003 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N201195-004 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N201195-005 | AP | 1 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | N201195-003 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N201195-004 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N201195-005 | AP | 1 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N201195-003 | AP | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N201195-004 | AP | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N201195-005 | AP | 1 | 79d66fd596c7… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N201195-003 | AP | 1 | 301d65b070ca… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| c7080c07-23f8-5aea-e053-2a95a90af985 | c482c813-1eb7-40dd-907a-845a7df112bf | 2021-07-13 | Boxed warning, Warnings, Adverse reactions | c482c813-1eb7-40dd-907a-845a7df112bf |
Adverse event summaries are temporarily unavailable. Other product information remains available.