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Drug Information for Paclitaxel Injection (Teva Parenteral Medicines, Inc): DOSAGE AND ADMINISTRATION
- CLINICAL PHARMACOLOGY
- INDICATIONS AND USAGE
- DOSAGE AND ADMINISTRATION
- HOW SUPPLIED
- Patient Information
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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 injection 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 injection 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 injection, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to paclitaxel injection, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before paclitaxel injection.
For patients with carcinoma of the ovary, the following regimens are 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). 1.Paclitaxel injection administered intravenously over 3 hours at a dose of 175 mg/m2 followed by cisplatin at a dose of 75 mg/m2; or 2.Paclitaxel injection 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 injection has been used at several doses and schedules; however, the optimal regimen is not yet clear. The recommended regimen is paclitaxel injection 135 mg/m2 or 175 mg/m2 administered intravenously over 3 hours every 3 weeks.
For patients with carcinoma of the breast, the following regimens are recommended (see CLINICAL STUDIES: Breast Carcinoma):
1)For the adjuvant treatment of node-positive breast cancer, the recommended regimen is paclitaxel injection, 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). 2)After failure of initial chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy, paclitaxel injection 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 injection 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 injection 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 45–50 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:
1)Reduce the dose of dexamethasone as 1 of the 3 premedication drugs to 10 mg PO (instead of 20 mg PO); 2)Initiate or repeat treatment with paclitaxel injection only if the neutrophil count is at least 1000 cells/mm3; 3)Reduce the dose of subsequent courses of paclitaxel injection by 20% for patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer); and 4)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 injection should not be repeated until the neutrophil count is at least 1500 cells/mm3 and the platelet count is at least 100,000 cells/mm3. paclitaxel injection should not be given to patients with AIDS-related Kaposi's sarcoma if the baseline or subsequent neutrophil count is less than 1000 cells/mm3. Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe peripheral neuropathy during paclitaxel injection therapy should have dosage reduced by 20% for subsequent courses of paclitaxel injection. 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.
TABLE 17 RECOMMENDATIONS FOR DOSING IN PATIENTS WITH HEPATIC IMPAIRMENT BASED ON CLINICAL TRIAL DATAThese 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 (eg, for AIDS-related Kaposi's sarcoma). Degree of Hepatic Impairment Transaminase Levels Bilirubin LevelsDifferences in criteria for bilirubin levels between the 3- and 24-hour infusion are due to differences in clinical trial design. Recommended Paclitaxel Injection DoseDosage recommendations are for the first course of therapy; further dose reduction in subsequent courses should be based on individual tolerance. 24-hour infusion <2 × ULN and =1.5 mg/dL 135 mg/m2 2 to <10 × ULN and =1.5 mg/dL 100 mg/m2 <10 × ULN and 1.6–7.5 mg/dL 50 mg/m2 =10 × ULN or >7.5 mg/dL Not recommended 3-hour infusion <10 × ULN and =1.25 × ULN 175 mg/m2 <10 × ULN and 1.26–2.0 × ULN 135 mg/m2 <10 × ULN and 2.01–5.0 × ULN 90 mg/m2 =10 × ULN or >5.0 × ULN Not recommended
Preparation and Administration Precautions
Paclitaxel injection is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised in handling paclitaxel injection. The use of gloves is recommended. If paclitaxel injection solution contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure, events have included tingling, burning, and redness. If paclitaxel injection contacts mucous membranes, the membranes should be flushed thoroughly with water. Upon inhalation, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration (see PRECAUTIONS: Injection Site Reaction).
Preparation for Intravenous Administration
Paclitaxel injection must be diluted prior to infusion. Paclitaxel injection should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer's Injection to a final concentration of 0.3 to 1.2 mg/mL. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (approximately 25°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Upon preparation, solutions may show haziness, which is attributed to the formulation vehicle. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line (0.22 micron) filter.
Data collected for the presence of the extractable plasticizer DEHP [di-(2-ethylhexyl) phthalate] show that levels increase with time and concentration when dilutions are prepared in PVC containers. Consequently, the use of plasticized PVC containers and administration sets is not recommended. Paclitaxel injection solutions should be prepared and stored in glass, polypropylene, or polyolefin containers. Non-PVC containing administration sets, such as those which are polyethylene-lined, should be used.
Paclitaxel injection should be administered through an in-line filter with a microporous membrane not greater than 0.22 microns. Use of filter devices such as IVEX-2® filters which incorporate short inlet and outlet PVC-coated tubing has not resulted in significant leaching of DEHP.
The Chemo Dispensing Pin™ device or similar devices with spikes should not be used with vials of paclitaxel injection since they can cause the stopper to collapse resulting in loss of sterile integrity of the paclitaxel injection solution.
Chemo Dispensing Pin™ is a trademark of B. Braun Medical Incorporated.
Unopened vials of paclitaxel injection are stable until the date indicated on the package when stored between 20°–25°C (68°–77°F), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Upon refrigeration, components in the paclitaxel injection vial may precipitate, but will redissolve upon reaching room temperature with little or no agitation. There is no impact on product quality under these circumstances. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded. Solutions for infusion prepared as recommended are stable at ambient temperature (approximately 25°C) and lighting conditions for up to 27 hours.
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