Docetaxel Prescribing Information
Docetaxel injection administered at 100 mg/m2was associated with deaths considered possibly or probably related to treatment in 2% (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/m2, 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.
Docetaxel injection administered at a dose of 100 mg/m2in 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/m2dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration , Clinical Studies ].
Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death.
Avoid docetaxel injection in 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 [see
For patients with isolated elevations of transaminase >1.5 × ULN, consider docetaxel injection dose modifications [see
Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of docetaxel injection therapy.
Perform frequent peripheral blood cell counts on all patients receiving docetaxel injection. Do not retreat patients with subsequent cycles of docetaxel injection until neutrophils recover to a level >1500 cells/mm3[see
A 25% reduction in the dose of docetaxel injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a docetaxel injection cycle [see Dosage and Administration ].
Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2to 100 mg/m2of docetaxel injection and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2and 75% of patients given 60 mg/m2. 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/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2but was very uncommon in patients given 60 mg/m2. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions , Clinical Studies ].
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 , Adverse Reactions ].
- Hypersensitivity to docetaxel or polysorbate 80
- Neutrophil counts of <1500 cells/mm3
Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the docetaxel infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with docetaxel injection [see
Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of docetaxel injection therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a docetaxel 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
Severe fluid retention has been reported following docetaxel injection 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 ]
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/m2. 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/m2. Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel injection to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, e.g., salt restriction, oral diuretic(s).
Warnings and Precautions (
Warnings and Precautions (
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 ]. 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 injection due to skin toxicity.
Warnings and Precautions (5.14) 05/2020
For all indications, toxicities may warrant dosage adjustments [see
Patients who are dosed initially at 100 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for more than 1 week, or severe or cumulative cutaneous reactions during docetaxel injection therapy should have the dosage adjusted from 100 mg/m2to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2to 55 mg/m2or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2and who do not experience febrile neutropenia, neutrophils <500 cells/mm3for 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.
Docetaxel injection in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm3. 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/m². Patients who experience grade 3 or 4 stomatitis should have their docetaxel injection dose decreased to 60 mg/m². 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/m2to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², treatment should be discontinued.
Patients who are dosed initially at 75 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for 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/m2. Patients who develop ≥ grade 3 peripheral neuropathy should have docetaxel injection treatment discontinued entirely.
For patients who are dosed initially at docetaxel injection 75 mg/m2in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, 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/m2. In patients who require a further dose reduction, a dose of 50 mg/m2is recommended. For cisplatin dosage adjustments, see manufacturers’ prescribing information.
Docetaxel injection should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm3for 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/m2to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.
Patients treated with docetaxel injection in combination with cisplatin and fluorouracil must receive antiemetics andappropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during thesecond and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenialasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despiteG-CSF use, the docetaxel injection dose should be reduced from 75 mg/m2to 60 mg/m2. If subsequent episodes of complicatedneutropenia occur the docetaxel injection dose should be reduced from 60 mg/m2to 45 mg/m2. In case of grade 4thrombocytopenia the docetaxel injection dose should be reduced from 75 mg/m2to 60 mg/m2.Do not retreat patients with subsequent cycles of docetaxel injection until neutrophils recover to a level >1,500 cells/mm3[see Contraindications ]. Avoid retreating patients until platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these toxicities persist [see
Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
Docetaxel Injection USP, 20 mg/1 mL single-dose vial: 20 mg docetaxel and 3 mg citric acid anhydrous in 1 mL in 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.
Docetaxel Injection USP, 80 mg/4 mL single-dose vial: 80 mg docetaxel and 12 mg citric acid anhydrous in 4 mL in 50/50 (v/v) ratio polysorbate 80/dehydrated alcohol.
Docetaxel injection is contraindicated in patients with:
- neutrophil counts of <1500 cells/mm3 [see Warnings andPrecautions(5.3 Hematologic Effects].
Perform frequent peripheral blood cell counts on all patients receiving docetaxel injection. Do not retreat patients with subsequent cycles of docetaxel injection until neutrophils recover to a level >1500 cells/mm3[see
Contraindications]. Avoid retreating patients until platelets recover to a level > 100,000 cells/mm3.A 25% reduction in the dose of docetaxel injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a docetaxel injection cycle [see Dosage and Administration ].
Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2to 100 mg/m2of docetaxel injection and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2and 75% of patients given 60 mg/m2. 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/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2but was very uncommon in patients given 60 mg/m2. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions , Clinical Studies ].
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 , Adverse Reactions
Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of docetaxel injection therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a docetaxel 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].
Enterocolitis and neutropenic colitis (typhlitis) have occurred in patients treated with docetaxel injection alone and in combination with other chemotherapeutic agents, despite the coadministration of G-CSF. Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis and neutropenic enterocolitis may develop at any time, and could lead to death as early as the first day of symptom onset. Monitor patients closely from onset of any symptoms of gastrointestinal toxicity. Inform patients to contact their healthcare provider with new, or worsening symptoms of gastrointestinal toxicity [see
For all indications, toxicities may warrant dosage adjustments [see
Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
Administer in a facility equipped to manage possible complications (e.g., anaphylaxis). Administer intravenously (IV) over 1 hr every 3 weeks. PVC equipment is not recommended.
- BC locally advanced or metastatic: 60 mg/m2to 100 mg/m2single agent
- BC adjuvant: 75 mg/m2administered 1 hour after doxorubicin 50 mg/m2and cyclophosphamide 500 mg/m2every 3 weeks for 6 cycles
- NSCLC: after platinum therapy failure: 75 mg/m2single agent
- NSCLC: chemotherapy-naive: 75 mg/m2followed by cisplatin 75 mg/m2
- HRPC: 75 mg/m2with 5 mg prednisone twice a day continuously
- GC: 75 mg/m2followed by cisplatin 75 mg/m2(both on day 1 only) followed by fluorouracil 750 mg/m2per day as a 24-hr IV (days 1 to 5), starting at end of cisplatin infusion
- SCCHN: 75 mg/m2followed by cisplatin 75 mg/m2IV (day 1), followed by fluorouracil 750 mg/m2per day as a 24-hr IV (days 1 to 5), starting at end of cisplatin infusion; for 4 cycles
- SCCHN: 75 mg/m2followed by cisplatin 100 mg/m2IV (day 1), followed by fluorouracil 1000 mg/m2per day as a 24-hr IV (days 1 to 4); for 3 cycles
- Premedicate with oral corticosteroids
- For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of docetaxel injection is 60 mg/m2to 100 mg/m2administered intravenously over 1 hour every 3 weeks.
- For the adjuvant treatment of operable node-positive breast cancer, the recommended docetaxel injection dose is 75 mg/m2administered 1 hour after doxorubicin 50 mg/m2and cyclophosphamide 500 mg/m2every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities [seeDosage and Administration].
- For treatment after failure of prior platinum-based chemotherapy, docetaxel injection was evaluated as monotherapy, and the recommended dose is 75 mg/m2administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized controlled trials [see Boxed Warning,Dosage and Administration , Warnings and Precautions , Clinical Studies ].
- For chemotherapy-naive patients, docetaxel injection wasevaluated in combination with cisplatin. The recommendeddose of docetaxel injection is 75 mg/m2administeredintravenously over 1 hour immediately followed by cisplatin75 mg/m2over 30 to 60 minutes every 3 weeks [see Dosage and Administration
- For gastric adenocarcinoma, the recommended dose of docetaxel injection is 75 mg/m2as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2per day given as a 24 hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration [see Dosage and Administration ].Induction Chemotherapy Followed by Chemoradiotherapy (TAX324)
For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of docetaxel injection is 75 mg/m2as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy [see Dosage and Administration ].
All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to docetaxel injection administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see
For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours, and 1 hour before the docetaxel infusion [see
Patients who are dosed initially at 100 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for more than 1 week, or severe or cumulative cutaneous reactions during docetaxel injection therapy should have the dosage adjusted from 100 mg/m2to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2to 55 mg/m2or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2and who do not experience febrile neutropenia, neutrophils <500 cells/mm3for 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.
Docetaxel injection in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm3. 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/m². Patients who experience grade 3 or 4 stomatitis should have their docetaxel injection dose decreased to 60 mg/m². 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/m2to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², treatment should be discontinued.
Patients who are dosed initially at 75 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for 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/m2. Patients who develop ≥ grade 3 peripheral neuropathy should have docetaxel injection treatment discontinued entirely.
For patients who are dosed initially at docetaxel injection 75 mg/m2in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, 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/m2. In patients who require a further dose reduction, a dose of 50 mg/m2is recommended. For cisplatin dosage adjustments, see manufacturers’ prescribing information.
Docetaxel injection should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm3for 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/m2to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.
Patients treated with docetaxel injection in combination with cisplatin and fluorouracil must receive antiemetics andappropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during thesecond and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenialasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despiteG-CSF use, the docetaxel injection dose should be reduced from 75 mg/m2to 60 mg/m2. If subsequent episodes of complicatedneutropenia occur the docetaxel injection dose should be reduced from 60 mg/m2to 45 mg/m2. In case of grade 4thrombocytopenia the docetaxel injection dose should be reduced from 75 mg/m2to 60 mg/m2.Do not retreat patients with subsequent cycles of docetaxel injection until neutrophils recover to a level >1,500 cells/mm3[see Contraindications ]. Avoid retreating patients until platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these toxicities persist [see
Docetaxel injection is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing docetaxel injection solutions. The use of gloves is recommended [see How Supplied / Storage and Handling
A 25% reduction in the dose of docetaxel injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a docetaxel injection cycle [see Dosage and Administration ].
Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2to 100 mg/m2of docetaxel injection and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2and 75% of patients given 60 mg/m2. 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/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2but was very uncommon in patients given 60 mg/m2. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions , Clinical Studies ].
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 , Adverse Reactions ].