Docetaxel - Warnings and Precautions
The following warnings and precautions are taken directly from the US FDA-approved drug label for Docetaxel. This is the same information dispensing pharmacists read.
\u26a0\ufe0f Boxed Warning (Highest FDA Alert)
WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION 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 ] . 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 x ULN concomitant with alkaline phosphatase >2.5 x ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase >1.5 x ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death. Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of Docetaxel Injection therapy [ see Warnings and Precautions ]. 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,
5 WARNINGS AND PRECAUTIONS • Second primary malignancies: In patients treated with Docetaxel Injection-containing regimens, monitor for delayed AML, MDS, NHL, and renal cancer. • Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur.
Severe skin toxicity may require dose adjustment. • Neurologic reactions: Reactions including paresthesia, dysesthesia, and pain may occur.
Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. • Eye disorders: Cystoid macular edema (CME) has been reported and requires treatment discontinuation. • Asthenia: Severe asthenia may occur and may require treatment discontinuation. • Embryo-fetal toxicity: Can cause fetal harm.
Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.12 , 8.1 , 8.3 ) • Alcohol content: The alcohol content in a dose of Docetaxel Injection may affect the central nervous system.
This may include impairment of a patient’s ability to drive or use machines immediately after infusion.
5.1 Toxic Deaths 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 , Clinical Studies ] .
5.2 Hepatic Impairment Patients with combined abnormalities of transaminases and alkaline phosphatase should not be treated with Docetaxel Injection [ see Boxed Warning , Use in Specific Populations , Clinical Studies ].
5.3 Hematologic Effects 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 ] .
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 , 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 ] .
5.4 Enterocolitis and Neutropenic Colitis 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.
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