DOCETAXEL: Package Insert and Label Information (Page 3 of 14)

5.10 Eye Disorders

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.

5.11 Asthenia

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.

5.12 Embryo-Fetal Toxicity

Based on findings from animal reproduction studies and its mechanism of action, docetaxel can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. Available data from case reports in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform the drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to initiating docetaxel. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of docetaxel. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of docetaxel [see Use in Specific Populations (8.1, 8.3)].

5.13 Alcohol Content

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.

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.

5.14 Tumor Lysis Syndrome

Tumor lysis syndrome has been reported with docetaxel [see Adverse Reactions (6.2)] . Patients at risk of tumor lysis syndrome (e.g., with renal impairment, hyperuricemia, bulky tumor) should be closely monitored prior to initiating Docetaxel Injection and periodically during treatment. Correction of dehydration and treatment of high uric acid levels are recommended prior to initiation of treatment.

6 ADVERSE REACTIONS

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.

6.1 Clinical Trials Experience

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 3.)

Table 3 : Summary of Adverse Reactions in Patients Receiving Docetaxel at 100 mg/m 2
Adverse Reaction All Tumor Types Normal LFTs *n=2045 % All Tumor Types Elevated LFTs n=61 % Breast Cancer Normal LFTs *n=965 %
*
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 Neutropenia
<2000 cells/mm 3 96 96 99
<500 cells/mm 3 Leukopenia 75 88 86
<4000 cells/mm 3 96 98 99
<1000 cells/mm 3 Thrombocytopenia 32 47 44
<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

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