Trade Names:Onxol- Solution for injection 6 mg/mL
Trade Names:Taxol- Solution for injection 6 mg/mL
Trade Names:Abraxane- Powder for injection, lyophilized (albumin-bound) 100 mgApo-Paclitaxel Injectable (Canada)
Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability inhibits the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis, further disrupting cell function.
89% to 98% protein bound.Onxol, Taxol
Extensive extravascular distribution or tissue binding; Vd is 227 to 688 L/m 2 at steady state with 24-h infusion.Abraxane
Vd is 632 L/m 2 .
Paclitaxel is metabolized primarily to 6α-hydroxypaclitaxel by isoenzymes CYP2C8 and to 2 minor metabolites, 3-p-hydroxypactlitaxel and 6α,-p-dihyroxypaclitaxel by CYP3A4.
Biphasic decline in plasma concentrations. Initial rapid decline represents distribution into the peripheral compartment and elimination of the drug; latter phase because of, in part, a relatively slow efflux from peripheral compartment. 14% excreted in urine, 71% in feces. Following 3- and 24-h infusions, the t ½ is 13.1 to 52.7 h and total body Cl is 12.2 to 23.8 L/h/m 2 .Abraxane
Biphasic decline in plasma concentrations. Initial rapid decline represents distribution into the peripheral compartment; slower second phase represents drug elimination. 4% excreted in urine, 20% in feces. Terminal t ½ is approximately 27 h and total body Cl is 15 L/h/m 2 .
Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 mo of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.Onxol, Taxol
Treatment of advanced carcinoma of the ovary.Taxol
Adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy; in combination with cisplatin for the treatment of non-small cell lung cancer (NSCLC) in patients who are not candidates for potentially curative surgery and/or radiation therapy; second-line treatment of AIDS-related Kaposi sarcoma.
Squamous cell head and neck cancer, small-cell lung cancer, bladder cancer, esophageal cancer, testicular cancer, endometrial cancer, prostate cancer, gastric cancer, germ cell tumors, refractory leukemia, and recurrent Wilms tumor in children.
Hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL (polyoxyethylated castor oil) or polyoxyl 35 castor oil; patients with solid tumors who have baseline neutrophil count of fewer than 1,500 cells/mm 3 or in patients with AIDS-related Kaposi sarcoma with baseline neutrophil counts of less than 1,000 cells/mm 3 .
IV Abraxane : 260 mg/m 2 administered over 30 min every 3 wk. For patients experiencing severe neutropenia (neutrophil less than 500 cells/mm 3 for 1 wk or longer) or severe sensory neuropathy, reduce dosage to 220 mg/m 2 for subsequent courses. For recurrence of severe neutropenia or severe sensory neuropathy, reduce dose to 180 mg/m 2 . For grade 3 sensory neuropathy, hold treatment until resolution to grade 1 or 2, and reduce dose for all subsequent courses of treatment. Onxol , Taxol : 175 mg/m 2 administered over 3 h every 3 wk.Ovarian CarcinomaAdults
IV Taxol : For previously untreated patients, give either regimen every 3 wk: 175 mg/m 2 administered over 3 h followed by cisplatin 75 mg/m 2 ; or 135 mg/m 2 over 24 h followed by cisplatin 75 mg/m 2 . Onxol , Taxol : For previously treated patients, 135 mg/m 2 or 175 mg/m 2 administered over 3 h every 3 wk.Adjuvant Treatment of Node-Positive Breast CarcinomaAdults
IV Taxol : 175 mg/m 2 over 3 h every 3 wk for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy.NSCLCAdults
IV Taxol : 135 mg/m 2 given every 3 wk administered over 24 h followed by cisplatin 75 mg/m 2 .AIDS-Related Kaposi SarcomaAdults
IV Taxol : 135 mg/m 2 administered over 3 h every 3 wk; or 100 mg/m 2 administered over 3 h every 2 wk.Pretreatment RegimenAdults
Onxol , Taxol only: Reduce incidence of hypersensitivity reactions. Premedicate with each of the following:Dexamethasone
20 mg PO 12 and 6 h before paclitaxel administration. Reduce each dexamethasone dose to 10 mg in AIDS patients.Diphenhydramine
50 mg IV 30 to 60 min before paclitaxel.Cimetidine
300 mg, ranitidine 50 mg IV 30 to 60 min before paclitaxel administration.Severe Neuropathy or Severe Neutropenia (less than 500 cells/mm 3 for more than 7 days)Adults
IV Onxol , Taxol : Reduce dose 20% for all subsequent courses.Hepatic Function ImpairmentAdults
IV Onxol , Taxol : For 135 mg/m 2 over 24 h regimen only: reduce dose of first course of therapy as follows: transaminase levels less than 2 × upper limits of normal (ULN) and bilirubin 1.5 mg/dL or less, give 135 mg/m 2 ; transaminase levels 2 to less than 10 × ULN and bilirubin 1.5 mg/dL or less, give 100 mg/m 2 ; transaminase levels less than 10 × ULN and bilirubin 1.6 to 7.5 mg/dL, give 50 mg/m 2 ; transaminase levels more than 10 × ULN or bilirubin more than 7.5 mg/dL, not recommended. For 175 mg/m 2 over 24 h regimen only: reduce dose of first course of therapy as follows: transaminase levels less than 10× ULN and bilirubin 1.25 × ULN or less, give 175 mg/m 2 ; transaminase levels less than 10 × ULN and bilirubin 1.26 to 2 × ULN, give 135 mg/m 2 ; transaminase levels less than 10 × ULN and bilirubin 2.01 to 5 × ULN, give 90 mg/m 2 ; transaminase levels 10 × ULN or more or bilirubin more than 5 × ULN, not recommended. Dose reduction for subsequent courses is based on individual tolerance.
Store unopened vials of Onxol and Taxol at controlled room temperature (68° to 77°F) in original package. Refrigeration or freezing do not adversely affect the stability of paclitaxel. Upon refrigeration, components in the vial may precipitate but will redissolve upon reaching room temperature with little or no agitation. Use diluted solution for infusion immediately. If not used immediately, the diluted solution is stable at ambient temperature (approximately 77°F) and lighting conditions for up to 27 h.
Store unopened vials of Abraxane at controlled room temperature in original package. Use reconstituted suspension immediately. If not used immediately, vials can be replaced in original carton to protect suspension from bright light and stored in refrigerator (36° to 46°F) for a max of 8 h. Some settling of the suspension may occur during storage. Ensure complete resuspension by mild agitation before use. Discard reconstituted suspension if precipitates are observed. Reconstituted suspension for injection in infusion bag is stable at ambient temperature and lighting conditions for up to 8 h.
Onxol contains dehydrated alcohol; consider possible CNS and other effects of alcohol.Cisplatin
Paclitaxel Cl may decrease when given after cisplatin, resulting in increased hematologic toxicity.CYP-450 2C8 and 3A4 inducers
May induce the metabolism of paclitaxel.CYP-450 2C8 and 3A4 inhibitors
May decrease the metabolism of paclitaxel.Doxorubicin
Paclitaxel may increase plasma concentrations of doxorubicin and its active metabolite, doxorubicinol.
None well documented.
The following adverse reactions data are based on the experience of 812 patients with ovarian cancer or breast cancer who were enrolled in 10 studies and received single-agent paclitaxel injection.
Abnormal ECG (23%); hypotension (12%); bradycardia (3%).
Peripheral neuropathy (60% [severe symptoms 3%]).
Nausea, vomiting (52%); diarrhea (38%); mucositis (31%).
Leukopenia, neutropenia (90%); anemia (78%); thrombocytopenia (20%); bleeding (14%).
Elevated alkaline phosphatase (22%); elevated AST (19%); elevated bilirubin (7%).
Hypersensitivity (41% [severe 2%]).
Injection site reaction (13%).
Myalgia, arthralgia (60% [severe symptoms 8%]).
Bone marrow infections (30%).
Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2% to 4% of patients. Fatal reactions have occurred despite premedication. Pretreat patients receiving paclitaxel with corticosteroids, diphenhydramine, and H 2 antagonists to prevent these reactions. Do not rechallenge patients who experience severe hypersensitivity reactions to paclitaxel with the drug. Contraindicated in patients with solid tumors who have baseline neutrophil counts of less than 1,500 cells/mm 3 and in AIDS-related Kaposi sarcoma patients with baseline neutrophil counts less than 1,000 cells/m 3 .Abraxane
Contraindicated in patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm 3 . An albumin form of paclitaxel may substantially affect a drugs functional properties relative to those of drug in solution. Do not substitute for or with other paclitaxel formulations.
Frequently monitor CBC, differential, and platelet counts. Closely monitor infusion site for possible infiltration during administration. Monitor vital signs frequently during infusion of Onxol and Taxol , especially during first hour. Perform continuous cardiac monitoring during subsequent therapy in patient who has developed a conduction abnormality during a previous paclitaxel infusion.
Category D .
Safety and efficacy not established.
Severe myelosuppression, neuropathy, and CV events may occur more frequently in elderly patients receiving Taxol or Onxol .
Do not use in patients with a history of severe hypersensitivity reactions to products containing Cremophor EL (polyoxyethylated castor oil) or polyoryl 35 castor oil. Pretreat patients with corticosteroids, diphenhydramine, and H 2 antagonists.
May require dosage reduction. Exercise caution when administering to patients with moderate to severe hepatic function impairment (bilirubin more than 1.5 mg/dL or more than 1.26 × ULN) and consider dose adjustments.
Because Abraxane contains human albumin, it carries an extremely remote risk for transmission of viral diseases or Creutzfeldt-Jakob disease.
Severe conduction abnormalities have been documented in fewer than 1% of patients during therapy, sometimes requiring a pacemaker. Hypotension, hypertension, and bradycardia also have been observed.
Peripheral neuropathy (glove-and-stocking distribution) occurs frequently.
Can cause local irritation or phlebitis.
Advise men to avoid procreation while receiving paclitaxel treatment.
Bone marrow suppression, peripheral neurotoxicity, mucositis.
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