Paclitaxel (3 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, POWDER.
Routes of administration: INJECTION, INTRAVENOUS.
Brand Names
- ABRAXANE
- PACLITAXEL
- TAXOL
Boxed Warning
Paclitaxel Injection, USP should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2%-4% of patients receiving paclitaxel in clinical trials. Fatal reactions have occurred in patients despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists. (See DOSAGE AND ADMINISTRATION section.) Patients who experience severe hypersensitivity reactions to paclitaxel should not be rechallenged with the drug. Paclitaxel therapy should not be given to patients with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm3 and should not be given to patients with AIDS-related Kaposi’s sarcoma if the baseline neutrophil count is less than 1,000 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving paclitaxel.
Indications and Usage
Paclitaxel Injection, USP is indicated as subsequent therapy for the treatment of advanced carcinoma of the ovary. As first-line therapy, paclitaxel is indicated in combination with cisplatin. Paclitaxel is indicated for the adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. In the clinical trial, there was an overall favorable effect on disease-free and overall survival in the total population of patients with receptor-positive and receptor-negative tumors, but the benefit has been specifically demonstrated by available data (median follow-up 30 months) only in the patients with estrogen and progesterone receptornegative tumors. (See CLINICAL STUDIES: Breast Carcinoma .) Paclitaxel Injection, USP is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. Paclitaxel, in combination with cisplatin, is indicated for the first-line treatment of nonsmall cell lung cancer in patients who are not candidates for potentially curative surgery and/or radiation therapy. Paclitaxel is indicated for the second-line treatment of AIDS-related Kaposi’s sarcoma.
Dosage and Administration
NOTE: Contact of the undiluted concentrate with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP [di-(2-ethylhexyl)phthalate], which may be leached from PVC infusion bags or sets, diluted paclitaxel solutions should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets. All patients should be premedicated prior to paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before paclitaxel, diphenhydramine (or its equivalent) 50 mg I.V. 30 to 60 minutes prior to paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) I.V. 30 to 60 minutes before paclitaxel. For patients with carcinoma of the ovary the following regimen is recommended: (see CLINICAL STUDIES: Ovarian Carcinoma ): 1) For previously untreated patients with carcinoma of the ovary, one of the following recommended regimens may be given every 3 weeks. In selecting the appropriate regimen, differences in toxicities should be considered (see Table 11 in ADVERSE REACTIONS: Disease-Specific Adverse Event Experiences ). a. Paclitaxel administered intravenously over 3 hours at a dose of 175 mg/m2 followed by cisplatin at a dose of 75 mg/m2; or b. Paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin at a dose of 75 mg/m2. 2) In patients previously treated with chemotherapy for carcinoma of the ovary, paclitaxel has been used at several doses and schedules; however, the optimal regimen is not yet clear. (See CLINICAL STUDIES: Ovarian Carcinoma section). The recommended regimen is paclitaxel 135 mg/m2 or 175 mg/m2 administered intravenously over 3 hours every 3 weeks. For patients with carcinoma of the breast , the following is recommended (see CLI
Contraindications
Paclitaxel Injection, USP is contraindicated in patients who have a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil, NF. Paclitaxel Injection, USP should not be used in patients with solid tumors who have baseline neutrophil counts of <1,500 cells/mm3 or in patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of <1,000 cells/mm3.
Adverse Reactions
Pooled Analysis of Adverse Event Experiences from Single-Agent Studies: Data in the following table are based on the experience of 812 patients (493 with ovarian carcinoma and 319 with breast carcinoma) enrolled in 10 studies who received single-agent Paclitaxel Injection, USP. Two hundred and seventy-five patients were treated in eight Phase 2 studies with paclitaxel doses ranging from 135 to 300 mg/m2 administered over 24 hours (in four of these studies, G-CSF was administered as hematopoietic support). Three hundred and one patients were treated in the randomized Phase 3 ovarian carcinoma study which compared two doses (135 or 175 mg/m2) and two schedules (3 or 24 hours) of paclitaxel. Two hundred and thirty-six patients with breast carcinoma received paclitaxel (135 or 175 mg/m2) administered over 3 hours in a controlled study. Table 10. Summarya of Adverse Events in Patients with Solid Tumors Receiving Single-Agent Paclitaxel Percent of Patients (n=812) • Bone Marrow - Neutropenia <2,000/mm3 <500/mm3 - Leukopenia <4,000/mm3 <1,000/mm3 - Thrombocytopenia <100,000/mm3 <50,000/mm3 - Anemia <11 g/dL <8 g/dL - Infections - Bleeding - Red Cell Transfusions - Platelet Transfusions 90 52 90 17 20 7 78 16 30 14 25 2 • Hypersensitivity Reactionb - All - Severe† 41 2 • Cardiovascular - Vital Sign Changesc - Bradycardia (n=537) - Hypotension (n=532) - Significant Cardiovascular Events 3 12 1 • Abnormal ECG - All Pts - Pts with normal baseline (n=559) 23 14 • Peripheral Neuropathy - Any symptoms - Severe symptoms† 60 3 • Myalgia/Arthralgia - Any symptoms - Severe symptoms† 60 8 • Gastrointestinal - Nausea and vomiting - Diarrhea - Mucositis 52 38 31 • Alopecia 87 • Hepatic (Pts with normal baseline and on study data) - Bilirubin elevations (n=765) - Alkaline phosphatase elevations (n=575) - AST (SGOT) elevations (n=591) 7 22 19 • Injection Site Reaction 13 a Based on worst course analysis. b All patients received premedication. c During the first 3 hours of infusion. † Seve
Overdosage
There is no known antidote for paclitaxel overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity (see PRECAUTIONS: Pediatric Use section).