Upon inhalation, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure, events have included tingling, burning, and redness.
To report SUSPECTED ADVERSE REACTIONS, contact Athenex Pharmaceutical Division, LLC. at 1-855-273-0154 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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).
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):
- 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).
- Paclitaxel administered intravenously over 3 hours at a dose of 175 mg/m2 followed by cisplatin at a dose of 75 mg/m2 ; or
- Paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin at a dose of 75 mg/m2.
- 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 CLINICAL STUDIES, Breast Carcinoma section):
- For the adjuvant treatment of node-positive breast cancer, the recommended regimen is paclitaxel, at a dose of 175 mg/m2 intravenously over 3 hours every 3 weeks for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy. The clinical trial used 4 courses of doxorubicin and cyclophosphamide (see CLINICAL STUDIES, Breast Carcinoma).
- After failure of initial chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy, paclitaxel at a dose of 175 mg/m2 administered intravenously over 3 hours every 3 weeks has been shown to be effective.
For patients with non-small cell lung carcinoma, the recommended regimen, given every 3 weeks, is paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m2 followed by cisplatin, 75 mg/m2.
For patients with AIDS-Related Kaposi’s Sarcoma, paclitaxel administered at a dose of 135 mg/m2 given intravenously over 3 hours every 3 weeks or at a dose of 100 mg/m2 given intravenously over 3 hours every 2 weeks is recommended (dose intensity 45 to 50 mg/m2 /week). In the 2 clinical trials evaluating these schedules (see CLINICAL STUDIES, AIDS-Related Kaposi’s Sarcoma), the former schedule (135 mg/m2 every 3 weeks) was more toxic than the latter. In addition, all patients with low performance status were treated with the latter schedule (100 mg/m2 every 2 weeks).
Based upon the immunosuppression in patients with advanced HIV disease, the following modifications are recommended in these patients:
- Reduce the dose of dexamethasone as 1 of the 3 premedication drugs to 10 mg PO (instead of 20 mg PO);
- Initiate or repeat treatment with paclitaxel only if the neutrophil count is at least 1,000 cells/mm3 ;
- Reduce the dose of subsequent courses of paclitaxel by 20% for patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer); and
- Initiate concomitant hematopoietic growth factor (G-CSF) as clinically indicated.
For the therapy of patients with solid tumors (ovary, breast and NSCLC), courses of paclitaxel should not be repeated until the neutrophil count is at least 1,500 cells/mm3 and the platelet count is at least 100,000 cells/mm3. Paclitaxel should not be given to patients with AIDS-related Kaposi’s sarcoma if the baseline or subsequent neutrophil count is less than 1,000 cells/mm3. Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe peripheral neuropathy during Paclitaxel Injection, USP therapy should have dosage reduced by 20% for subsequent courses of paclitaxel. The incidence of neurotoxicity and the severity of neutropenia increase with dose.
Patients with hepatic impairment may be at increased risk of toxicity, particularly grade III–IV myelosuppression (see CLINICAL PHARMACOLOGY and PRECAUTIONS, Hepatic). Recommendations for dosage adjustment for the first course of therapy are shown in Table 17 for both 3- and 24-hour infusions. Further dose reduction in subsequent courses should be based on individual tolerance. Patients should be monitored closely for the development of profound myelosuppression.
a These recommendations are based on dosages for patients without hepatic impairment of 135 mg/m2 over 24 hours or 175 mg/m2 over 3 hours; data are not available to make dose adjustment recommendations for other regimens (e.g., for AIDS-related Kaposi’s sarcoma).
b Differences in criteria for bilirubin levels between the 3- and 24-hour infusion are due to differences in clinical trial design.
c Dosage recommendations are for the first course of therapy; further dose reduction in subsequent courses should be based on individual tolerance.
|Degree of Hepatic Impairment||Recommended Paclitaxel Dose c|
|Transaminase Levels||Bilirubin Levels b|
|<2 x ULN||and||≤1.5 mg/dL||135 mg/m2|
|2 to <10 x ULN||and||≤1.5 mg/dL||100 mg/m2|
|<10 x ULN||and||1.6-7.5 mg/dL||50 mg/m2|
|≥10 x ULN||or||>7.5 mg/dL||Not recommended|
|<10 x ULN||and||≤1.25 x ULN||175 mg/m2|
|<10 x ULN||and||1.26-2.0 x ULN||135 mg/m2|
|<10 x ULN||and||2.01-5.0 x ULN||90 mg/m2|
|≥10 x ULN||or||>5.0 x ULN||Not recommended|
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