DailyMed Label: Paclitaxel

DailyMed Label: PACLITAXEL

2023

DailyMed Prescription

PACLITAXEL

paclitaxel

Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.

NDC: 23155-882

NDC: 23155-883

NDC: 23155-884

NDC: 23155-882

NDC: 23155-883

NDC: 23155-884

NDC: 23155-882

NDC: 23155-882

NDC: 23155-883

NDC: 23155-883

NDC: 23155-884

NDC: 23155-884

Paclitaxel Injection, USP is a clear colorless to slightly yellow viscous solution. It is supplied as a nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel, 527 mg of Polyoxyl 35 Castor Oil, NF, 49.7% (v/v) Dehydrated Alcohol, USP and 2 mg Citric Acid, USP. Paclitaxel is a natural product with antitumor activity. Paclitaxel is obtained via an extraction process from Taxus X media ‘ Hicksii’. The chemical name for paclitaxel is (2a R ,4 S ,4a S ,6 R ,9 S ,11 S ,12 S ,12a R ,12b S )-1,2a,3,4,4a,6,9,10,11, 12,12a,12b-Dodecahydro-4,6,9,11,12,-12b-hexahydroxy-4a,8, 13,13-tetramethyl-7,11-methano-5 H -cyclodeca [3,4] benz [1,2-b] oxet-5-one 6,12b-diacetate, 12-benzoate, 9-ester with (2 R ,3 S ) -N -benzoyl-3-phenylisoserine. Paclitaxel has the following structural formula: Paclitaxel is a white to off-white crystalline powder with the empirical formula C 47 H 51 NO 14 and molecular weight of 853.9. It is highly lipophilic, insoluble in water, and melts at around 216 to 217°C.

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.

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/m 2 followed by cisplatin at a dose of 75 mg/m 2 ; or b.   Paclitaxel administered intravenously over 24 hours at a dose of 135 mg/m 2 followed by cisplatin at a dose of 75 mg/m 2 . 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/m 2 or 175 mg/m 2 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): 1)   For the adjuvant treatment of node-positive breast cancer, the recommended regimen is paclitaxel, at a dose of 175 mg/m 2 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/m 2 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/m 2 followed by cisplatin, 75 mg/m 2 . For patients with AIDS-related Kaposi’s sarcoma, paclitaxel administered at a dose of 135 mg/m 2 given intravenously over 3 hours every 3 weeks or at a dose of 100 mg/m 2 given intravenously over 3 hours every 2 weeks is recommended (dose intensity 45 to 50 mg/m 2 /week). In the 2 clinical trials evaluating these schedules (see CLINICAL STUDIES: AIDS-Related Kaposi’s Sarcoma ), the former schedule (135 mg/m 2 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/m 2 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/mm 3 ; 3)   Reduce the dose of subsequent courses of paclitaxel by 20% for patients who experience severe neutropenia (neutrophil <500 cells/mm 3 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/mm 3 and the platelet count is at least 100,000 cells/mm 3 . 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/mm 3 . Patients who experience severe neutropenia (neutrophil <500 cells/mm 3 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 Data a Degree of Hepatic Impairment Recommended Paclitaxel Dose c Transaminase Levels Bilirubin Levels b 24-Hour Infusion <2 x ULN and ≤1.5 mg/dL 135 mg/m 2 2 to <10 x ULN and ≤1.5 mg/dL 100 mg/m 2 <10 x ULN and 1.6-7.5 mg/dL 50 mg/m 2 ≥10 x ULN or >7.5 mg/dL Not recommended 3-Hour Infusion <10 x ULN and ≤1.25 x ULN 175 mg/m 2 <10 x ULN and 1.26-2.0 x ULN 135 mg/m 2 <10 x ULN and 2.01-5.0 x ULN 90 mg/m 2 ≥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/m 2 over 24 hours or 175 mg/m 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. 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 Reaction section.) 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.

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/mm 3 or in patients with AIDS-related kaposi’s sarcoma with baseline neutrophil counts of <1,000 cells/mm 3 .

Contact of the undiluted concentrate with plasticized polyvinyl chloride (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, USP solutions should preferably be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets. 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. Drug Interactions:  In a Phase I trial using escalating doses of paclitaxel (110 to 200 mg/m 2 ) and cisplatin (50 or 75 mg/m 2 ) given as sequential infusions, myelosuppression was more profound when paclitaxel was given after cisplatin than with the alternate sequence (i.e., paclitaxel before cisplatin). Pharmacokinetic data from these patients demonstrated a decrease in paclitaxel clearance of approximately 33% when paclitaxel was administered following cisplatin. The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering paclitaxel concomitantly with known substrates or inhibitors of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution should be exercised when paclitaxel is concomitantly administered with known substrates (eg, midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (eg, rifampin and carbamazepine) of CYP3A4. (See CLINICAL PHARMACOLOGY section.) Caution should also be exercised when paclitaxel is concomitantly administered with known substrates (eg. repaglinide and rosiglitazone), inhibitors (eg, gemfibrozil), and inducers (eg, rifampin) of CYP2C8. (See CLINICAL PHARMACOLOGY. ) Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials. Reports in the literature suggest that plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination. Hematology: Paclitaxel therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm 3 . In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving paclitaxel. Patients should not be retreated with subsequent cycles of paclitaxel until neutrophils recover to a level >1,500 cells/mm 3 and platelets recover to a level >100,000 cells/mm 3 . In the case of severe neutropenia (<500 cells/mm 3 for seven days or more) during a course of paclitaxel therapy, a 20% reduction in dose for subsequent courses of therapy is recommended. For patients with advanced HIV disease and poor-risk AIDS-related Kaposi’s sarcoma, paclitaxel, at the recommended dose for this disease, can be initiated and repeated if the neutrophil count is at least 1,000 cells/mm 3 . Hypersensitivity Reactions: Patients with a history of severe hypersensitivity reactions to products containing Polyoxyl 35 Castor Oil, NF (e.g., cyclosporin for injection concentrate and teniposide for injection concentrate) should not be treated with paclitaxel. In order to avoid the occurrence of severe hypersensitive reactions, all patients treated with paclitaxel should be premedicated with corticosteroids (such as dexamethasone), diphenhydramine and H 2 antagonists (such as cimetidine or ranitidine). Minor symptoms such as flushing, skin reactions, dyspnea, hypotension, or tachycardia do not require interruption of therapy. However, severe reactions, such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria require immediate discontinuation of paclitaxel and aggressive symptomatic therapy. Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel. Cardiovascular: Hypotension, bradycardia, and hypertension have been observed during administration of Paclitaxel Injection, USP, but generally do not require treatment. Occasionally paclitaxel infusions must be interrupted or discontinued because of initial or recurrent hypertension. Frequent vital sign monitoring, particularly during the first hour of paclitaxel infusion, is recommended. Continuous cardiac monitoring is not required except for patients with serious conduction abnormalities. (See WARNINGS section.) When paclitaxel is used in combination with doxorubicin for treatment of metastatic breast cancer, monitoring of cardiac function is recommended. (See ADVERSE REACTIONS. ) Nervous System: Although the occurrence of peripheral neuropathy is frequent, the development of severe symptomatology is unusual and requires a dose reduction of 20% for all subsequent courses of paclitaxel. Paclitaxel contains Dehydrated Alcohol USP, 396 mg/mL; consideration should be given to possible CNS and other effects of alcohol. (See PRECAUTIONS: Pediatric Use section.) Hepatic: There is limited evidence that the myelotoxicity of Paclitaxel may be exacerbated in patients with serum total bilirubin >2 times ULN (See CLINICAL PHARMACOLOGY ). Extreme caution should be exercised when administering Paclitaxel to such patients, with dose reduction as recommended in DOSAGE AND ADMINISTRATION , TABLE 17. Injection Site Reaction: Injection site reactions, including reactions secondary to extravasation, were usually mild and consisted of erythema, tenderness, skin discoloration, or swelling at the injection site. These reactions have been observed more frequently with the 24-hour infusion than with the 3-hour infusion. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel at a different site, i.e., “recall”, has been reported. More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have been reported. In some cases the onset of the injection site reaction either occurred during a prolonged infusion or was delayed by a week to ten days. A specific treatment for extravasation reactions is unknown at this time. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.

Paclitaxel Injection, USP (6 mg/mL) is supplied in the following: NDC No. Fill volume Package 23155-882-31 5 mL fill in 5 mL Multiple-dose vial One Multiple-dose vial in one carton 23155-883-31 16.7 mL fill in 20 mL Multiple-dose vial One Multiple-dose vial in one carton 23155-884-31 50 mL fill in 50 mL Multiple-dose vial One Multiple-dose vial in one carton 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.

Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of 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. Following intravenous administration of paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment. Pharmacokinetic parameters of paclitaxel following 3- and 24-hour infusions of paclitaxel at dose levels of 135 and 175 mg/m 2 were determined in a Phase 3 randomized study in ovarian cancer patients and are summarized in the following table: Table 1. Summary of Pharmacokinetic Parameters – Mean Values Dose (mg/m 2 ) Infusion Duration (h) N (patients) C max (ng/mL) AUC(0 -∞) (ng•h/mL) T -HALF (h) CL T (L/h/m 2 ) 135 24 2 195 6,300 52.7 21.7 175 24 4 365 7,993 15.7 23.8 135 3 7 2,170 7,952 13.1 17.7 175 3 5 3,650 15,007 20.2 12.2 C max = Maximum plasma concentration AUC (0-∞) = Area under the plasma concentration-time curve from time 0 to infinity CL T = Total body clearance It appeared that with the 24-hour infusion of paclitaxel, a 30% increase in dose (135 mg/m 2 versus 175 mg/m 2 ) increased the C max by 87%, whereas the AUC (0-∞) remained proportional. However, with a 3-hour infusion, for a 30% increase in dose, the C max and AUC (0-∞) were increased by 68% and 89%, respectively. The mean apparent volume of distribution at steady state, with the 24-hour infusion of paclitaxel, ranged from 227 to 688 L/m 2 indicating extensive extravascular distribution and/or tissue binding of paclitaxel. The pharmacokinetics of paclitaxel were also evaluated in adult cancer patients who received single doses of 15 to 135 mg/m2 given by 1-hour infusions (n=15), 30 to 275 mg/m2 given by 6-hour infusions (n=36), and 200 to 275 mg/m2 given by 24-hour infusions (n=54) in Phase 1 & 2 studies. Values for CLT and volume of distribution were consistent with the findings in the Phase 3 study. The pharmacokinetics of paclitaxel in patients with AIDS-related Kaposi’s sarcoma have not been studied. In vitro studies of binding to human serum proteins, using paclitaxel concentrations ranging from 0.1 to 50 mcg/mL, indicate that between 89% to 98% of drug is bound; the presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. After intravenous administration of 15 to 275 mg/m 2 doses of Paclitaxel Injection, USP as 1-, 6- or 24-hour infusions, mean values for cumulative urinary recovery of unchanged drug ranged from 1.3% to 12.6% of the dose, indicating extensive non-renal clearance. In five patients administered a 225 or 250 mg/m 2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine. Total recovery of radioactivity ranged from 56% to 101% of the dose. Paclitaxel represented a mean of 5% of the administered radioactivity recovered in the feces, while metabolites, primarily 6α- hydroxypaclitaxel, accounted for the balance. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6α-hydroxypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’- p -hydroxypaclitaxel and 6α, 3’- p -dihydroxy- paclitaxel, by CYP3A4. In vitro , the metabolism of paclitaxel to6α-hydroxypaclitaxel was inhibited by a number of agents (ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporin, teniposide, etoposide, and vincristine), but the concentrations used exceeded those found in vivo following normal therapeutic doses. Testosterone, 17α-ethinyl estradiol, retinoic acid, and quercetin, a specific inhibitor of CYP2C8, also inhibited the formation of 6α-hydroxypaclitaxel in vitro . The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with compounds that are substrates, inducers, or inhibitors of CYP2C8 and/or CYP3A4. (See PRECAUTIONS:  Drug Interactions section.) The disposition and toxicity of paclitaxel 3-hour infusion were evaluated in 35 patients with varying degrees of hepatic function. Relative to patients with normal bilirubin, plasma paclitaxel exposure in patients with abnormal serum bilirubin ≤2 times upper limit of normal (ULN) administered 175 mg/m 2 was increased, but with no apparent increase in the frequency or severity of toxicity. In 5 patients with serum total bilirubin >2 times ULN, there was a statistically nonsignificant higher incidence of severe myelosuppression, even at a reduced dose (110 mg/m 2 ), but no observed increase in plasma exposure. (See PRECAUTIONS: Hepatic and DOSAGE AND ADMINISTRATION.) The effect of renal or hepatic dysfunction on the disposition of paclitaxel has not been investigated. Possible interactions of paclitaxel with concomitantly administered medications have not been formally investigated.

Paclitaxel Injection, USP 30 mg/5 mL, 6 mg/mL Rx only CAUTION: DILUTION REQUIRED PRIOR TO IV INFUSION Multiple Dose Vial Cytotoxic Agent Paclitaxel Injection, USP 100 mg/16.7 mL, 6 mg/mL Rx only CAUTION: DILUTION REQUIRED PRIOR TO IV INFUSION Multiple Dose Vial Cytotoxic Agent Paclitaxel Injection, USP 300 mg/50 mL, 6 mg/mL Rx only CAUTION: DILUTION REQUIRED PRIOR TO IV INFUSION Multiple Dose Vial Cytotoxic Agent