DOCETAXEL- docetaxel anhydrous injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DOCETAXEL ANHYDROUS (UNII: 699121PHCA) (DOCETAXEL ANHYDROUS - UNII:699121PHCA)

Available from:

Ingenus Pharmaceuticals, LLC

INN (International Name):

DOCETAXEL ANHYDROUS

Composition:

DOCETAXEL ANHYDROUS 10 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 metastatic castration-resistant 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). Docetaxel Injection is contraindicated in patients with: - neutrophil counts of <1500 cells/mm3 [see Warnings and Precautions (5.3) ]. - a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [see Warnings and Precautions (5.5) ]. Risk Summary Based on findings in animal reproduction studies and its mechanism of action, Docetaxel Injection 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. Docetaxel Injection contains alcohol which can interfere with neurobehavioral development (see Clinical Considerations ). In animal reproductive studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused an increased incidence of 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 (see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Docetaxel Injection contains alcohol [see Warnings and Precautions (5.13) ]. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal data Intravenous administration of ≥0.3 and 0.03 mg/kg/day docetaxel to pregnant rats and rabbits, respectively, during the period of organogenesis caused an increased incidence of intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays. Maternal toxicity was also observed at these doses, which were approximately 0.02 and 0.003 times the daily maximum recommended human dose based on body surface area, respectively. Risk Summary There is no information regarding the presence of docetaxel in human milk, or on its effects on milk production or the breastfed child. No lactation studies in animals have been conducted. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Docetaxel Injection and for 1 week after the last dose. Based on findings in animals, Docetaxel Injection can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating Docetaxel Injection. Contraception Females Based on genetic toxicity findings, advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of Docetaxel Injection. Males Based on genetic toxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of Docetaxel Injection. Infertility Based on findings in animal studies, Docetaxel Injection may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1) ]. The alcohol content of Docetaxel Injection should be taken into account when given to pediatric patients [see Warnings and Precautions (5.13) ]. The efficacy of docetaxel in pediatric patients as monotherapy or in combination has not been established. The overall safety profile of docetaxel in pediatric patients receiving monotherapy or TCF was consistent with the known safety profile in adults. Docetaxel has been studied in a total of 289 pediatric patients: 239 in 2 trials with monotherapy and 50 in combination treatment with cisplatin and 5-fluorouracil (TCF). Docetaxel Monotherapy Docetaxel monotherapy was evaluated in a dose-finding phase 1 trial in 61 pediatric patients (median age 12.5 years, range 1-22 years) with a variety of refractory solid tumors. The recommended dose was 125 mg/m2 as a 1-hour intravenous infusion every 21 days. The primary dose limiting toxicity was neutropenia. The recommended dose for docetaxel monotherapy was evaluated in a phase 2 single-arm trial in 178 pediatric patients (median age 12 years, range 1-26 years) with a variety of recurrent/refractory solid tumors. Efficacy was not established with tumor response rates ranging from one complete response (CR) (0.6%) in a patient with undifferentiated sarcoma to four partial responses (2.2%) seen in one patient each with Ewing Sarcoma, neuroblastoma, osteosarcoma, and squamous cell carcinoma. Docetaxel in Combination Docetaxel was studied in combination with cisplatin and 5-fluorouracil (TCF) versus cisplatin and 5-fluorouracil (CF) for the induction treatment of nasopharyngeal carcinoma (NPC) in pediatric patients prior to chemoradiation consolidation. Seventy-five patients (median age 16 years, range 9 to 21 years) were randomized (2:1) to docetaxel (75 mg/m2 ) in combination with cisplatin (75 mg/m2 ) and 5-fluorouracil (750 mg/m2 ) (TCF) or to cisplatin (80 mg/m2 ) and 5-fluorouracil (1000 mg/m2 /day) (CF). The primary endpoint was the CR rate following induction treatment of NPC. One patient out of 50 in the TCF group (2%) had a complete response while none of the 25 patients in the CF group had a complete response. Pharmacokinetics Pharmacokinetic parameters for docetaxel were determined in 2 pediatric solid tumor trials. Following docetaxel administration at 55 mg/m2 to 235 mg/m2 in a 1-hour intravenous infusion every 3 weeks in 25 patients aged 1 to 20 years (median 11 years), docetaxel clearance was 17.3±10.9 L/h/m2 . Docetaxel was administered in combination with cisplatin and 5-fluorouracil (TCF), at dose levels of 75 mg/m2 in a 1-hour intravenous infusion day 1 in 28 patients aged 10 to 21 years (median 16 years, 17 patients were older than 16). Docetaxel clearance was 17.9±8.75 L/h/m2 , corresponding to an AUC of 4.20±2.57 μg●h/mL. In summary, the body surface area adjusted clearance of docetaxel monotherapy and TCF combination in children were comparable to those in adults [see Clinical Pharmacology (12.3) ]. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in elderly patients. Non-small Cell Lung Cancer In a study conducted in chemotherapy-naїve 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 less than 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 less than 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-naїve, 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 Injection 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 Injection 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 Injection 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. Avoid Docetaxel Injection in patients with bilirubin >ULN and patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [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 (5.13)] .

Product summary:

Docetaxel Injection, USP is supplied in single-dose or multiple-dose vials as a sterile, pyrogen-free, non-aqueous solution to pale yellow solution. Discard unused portion of the single-dose vial. The following strengths are available in a one-vial formulation: Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature]. Retain in the original package to protect from light. Freezing does not adversely affect the product. After first use and following multiple needle entries and product withdrawals, Docetaxel Injection multiple-dose vials are stable for up to 28 days when stored between 2°C and 8°C (36°F and 46°F) and protected from light. Docetaxel Injection is a hazardous drug. Follow applicable special handling and disposal procedures.1

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

DOCETAXEL- DOCETAXEL ANHYDROUS INJECTION, SOLUTION
INGENUS PHARMACEUTICALS, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DOCETAXEL INJECTION
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DOCETAXEL
INJECTION.
DOCETAXEL INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1996
WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA,
HYPERSENSITIVITY REACTIONS, AND FLUID RETENTION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
TREATMENT-RELATED MORTALITY INCREASES WITH ABNORMAL LIVER FUNCTION, AT
HIGHER DOSES,
AND IN PATIENTS WITH NSCLC AND PRIOR PLATINUM-BASED THERAPY RECEIVING
DOCETAXEL AT
100 MG/M (5.1)
AVOID USE OF DOCETAXEL INJECTION IF BILIRUBIN > ULN, OR IF AST AND/OR
ALT > 1.5 × ULN
CONCOMITANT WITH ALKALINE PHOSPHATASE > 2.5 × ULN. LFT ELEVATIONS
INCREASE RISK OF
SEVERE OR LIFE-THREATENING COMPLICATIONS. OBTAIN LFTS BEFORE EACH
TREATMENT CYCLE
(5.2)
DO NOT ADMINISTER DOCETAXEL INJECTION TO PATIENTS WITH NEUTROPHIL
COUNTS <1500
CELLS/MM . OBTAIN FREQUENT BLOOD COUNTS TO MONITOR FOR NEUTROPENIA
(4,5.3)
SEVERE HYPERSENSITIVITY, INCLUDING FATAL ANAPHYLAXIS, HAS BEEN
REPORTED IN PATIENTS
WHO RECEIVED DEXAMETHASONE PREMEDICATION. SEVERE REACTIONS REQUIRE
IMMEDIATE
DISCONTINUATION OF DOCETAXEL INJECTION AND ADMINISTRATION OF
APPROPRIATE THERAPY
(5.5)
CONTRAINDICATED IF HISTORY OF SEVERE HYPERSENSITIVITY REACTIONS TO
DOCETAXEL OR TO
DRUGS FORMULATED WITH POLYSORBATE 80 (4)
SEVERE FLUID RETENTION MAY OCCUR DESPITE DEXAMETHASONE (5.6)
INDICATIONS AND USAGE
Docetaxel Injection is a microtubule inhibitor indicated for:
BREAST CANCER (BC):single agent for locally advanced or metastatic BC
after chemotherapy failure;
and with doxorubicin and cyclophosphamide as adjuvant treatment of
operable node-positive BC (1.1)
NON-SMALL CELL LUNG CANCER (NSCLC):single agent for locally advanced
or metastatic NSCLC after
platinum therapy failure; and with cisplatin for unresectable, locally
advanced or metastatic untreated
NSCLC (1.2