DOCETAXEL (Page 5 of 20)

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:

• Toxic Deaths [see Boxed Warning, Warnings and Precautions (5.1)]
• Hepatic Impairment [see Boxed Warning, Warnings and Precautions (5.2)]
• Hematologic Effects [see Boxed Warning, Warnings and Precautions (5.3)]
• Enterocolitis and Neutropenic Colitis [see Warnings and Precautions (5.4)]
• Hypersensitivity Reactions [see Boxed Warning, Warnings and Precautions (5.5)]
• Fluid Retention [see Boxed Warning, Warnings and Precautions (5.6)]
• Second Primary Malignancies [see Warnings and Precautions (5.7)]
• Cutaneous Reactions [see Warnings and Precautions (5.8)]
• Neurologic Reactions [see Warnings and Precautions (5.9)]
• Eye Disorders [see Warnings and Precautions (5.10)]
• Asthenia [see Warnings and Precautions (5.11)]
• Alcohol Content [see Warnings and Precautions (5.13)]

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