Paclitaxel: Package Insert and Label Information (Page 4 of 5)

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).

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 Carcinomasection). 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 Carcinomasection):

1) 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).

2) 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 45–50 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 only if the neutrophil count is at least 1,000 cells/mm3 ;

3) 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

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 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.

Hepatic Impairment: 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 Dataa

Degree of Hepatic Impairment

Recommended Paclitaxel Dosec

Transaminase

Levels

Bilirubin Levelsb

24-Hour Infusion

<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

3-Hour Infusion

<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

a These recommendations are based on dosages for patients without hepatic imairement 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).

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.

Preparation and Administration Precautions: Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1–4 To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing paclitaxel Injection. If paclitaxel 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 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 Reactionsection.)

Preparation for Intravenous Administration: Paclitaxel must be diluted prior to infusion. Paclitaxel 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 I.V. 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 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 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 since they can cause the stopper to collapse resulting in loss of sterile integrity of the paclitaxel solution.

Stability: Unopened vials of Paclitaxel Injection, USP are stable until the date indicated on the package when stored between 20° to 25°C (68° to 77°F), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product. Upon refrigeration components in the paclitaxel 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.

HOW SUPPLIED

Paclitaxel Injection, USP (6 mg/mL) is supplied in the following:

Unit of Sale Concentration
NDC 61703-342-09 Carton containing 1 multiple-dose vial 30 mg/5 mL(6 mg/mL)
NDC 61703-342-22 Carton containing 1 multiple-dose vial 100 mg/16.7 mL(6 mg/mL)
NDC 61703-342-50 Carton containing 1 multiple-dose vial 300 mg/50 mL(6 mg/mL)

Storage: Store the vials in original cartons between 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Retain in the original package to protect from light.

Handling and Disposal: See DOSAGE AND ADMINISTRATION: Preparation and Administration Precautions.

REFERENCES

  1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004165.
  2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling occupational exposure to hazardous drugs. OSHA, 1999.
    http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.
  3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.
  4. Polovich M, White JM, Kelleher LO, eds. 2005. Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society.

*DaunoXome® is a registered trademark of Gilead Sciences, Inc.

DOXIL® is a registered trademark of ALZA Corporation.

IVEX-2® is a registered trademark of the Millipore Corporation.

Chemo Dispensing Pin™ is a trademark of B. Braun Medical Incorporated.

Distributed by Hospira Inc., Lake Forest, IL 60045 USA

logo

LAB-1315-2.0

Revised: 04/2021

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.