Rx Only
(Patient Information Enclosed)
(Patient Information Enclosed)
WARNING
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.
ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.
ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.
DESCRIPTION
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is an albumin-bound form of paclitaxel with a mean particle size of approximately 130 nanometers. ABRAXANE is supplied as a white to yellow, sterile, lyophilized powder for reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. Each single-use vial contains 100 mg of paclitaxel and approximately 900 mg of human albumin. Each milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel. ABRAXANE is free of solvents.
The active agent in ABRAXANE® is paclitaxel, a natural product with antitumor activity. Paclitaxel is obtained from Taxus media. The chemical name for paclitaxel is 5ß,20-Epoxy-1,2α,4,7α,10ß,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine.
Paclitaxel has the following structural formula:
Paclitaxel is a white to off-white crystalline powder with the empirical formula C47H51NO14 and a molecular weight of 853.91. It is highly lipophilic, insoluble in water, and melts at approximately 216°C to 217°C.
The active agent in ABRAXANE® is paclitaxel, a natural product with antitumor activity. Paclitaxel is obtained from Taxus media. The chemical name for paclitaxel is 5ß,20-Epoxy-1,2α,4,7α,10ß,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine.
Paclitaxel has the following structural formula:
Paclitaxel is a white to off-white crystalline powder with the empirical formula C47H51NO14 and a molecular weight of 853.91. It is highly lipophilic, insoluble in water, and melts at approximately 216°C to 217°C.
CLINICAL PHARMACOLOGY
Mechanism of Action
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is an 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. Paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Human Pharmacokinetics
The pharmacokinetics of total paclitaxel following 30 and 180-minute infusions of ABRAXANE at dose levels of 80 to 375 mg/m2 were determined in clinical studies. Dose levels of mg/m2 refer to mg of paclitaxel in ABRAXANE. Following intravenous administration of ABRAXANE, paclitaxel plasma concentrations declined in a biphasic manner, the initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination. The terminal half-life was about 27 hours.
The drug exposure (AUCs) was dose proportional over 80 to 375 mg/m2 and the pharmacokinetics of paclitaxel for ABRAXANE® were independent of the duration of administration. At the recommended ABRAXANE clinical dose, 260 mg/m2, the mean maximum concentration of paclitaxel, which occurred at the end of the infusion, was 18,741 ng/mL. The mean total clearance was 15 L/hr/m2. The mean volume of distribution was 632 L/m2; the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel.
The pharmacokinetic data of 260 mg/m2 ABRAXANE administered over 30 minutes was compared to the pharmacokinetics of 175 mg/m2 paclitaxel injection over 3 hours. The clearance of ABRAXANE was larger (43%) than for the clearance of paclitaxel injection and the volume of distribution of ABRAXANE was also higher (53%). Differences in Cmax and Cmax corrected for dose reflected differences in total dose and rate of infusion. There were no differences in terminal half-lives.
In vitro studies of binding to human serum proteins, using paclitaxel concentrations ranging from 0.1 to 50 µg/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 a 30-minute infusion of 260 mg/m2 doses of ABRAXANE, the mean values for cumulative urinary recovery of unchanged drug (4%) indicated extensive non-renal clearance. Less than 1% of the total administered dose was excreted in urine as the metabolites 6a-hydroxypaclitaxel and 3’-p-hydroxypaclitaxel. Fecal excretion was approximately 20% of the total dose administered.
In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydroxypaclitaxel by CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4. In vitro, the metabolism of paclitaxel to 6a-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, 17a-ethinyl estradiol, retinoic acid, and quercetin, a specific inhibitor of CYP2C8, also inhibited the formation of 6a-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). The effect of renal or hepatic dysfunction on the disposition of ABRAXANE® has not been investigated.
Possible interactions of paclitaxel with concomitantly administered medications have not been formally investigated.
The drug exposure (AUCs) was dose proportional over 80 to 375 mg/m2 and the pharmacokinetics of paclitaxel for ABRAXANE® were independent of the duration of administration. At the recommended ABRAXANE clinical dose, 260 mg/m2, the mean maximum concentration of paclitaxel, which occurred at the end of the infusion, was 18,741 ng/mL. The mean total clearance was 15 L/hr/m2. The mean volume of distribution was 632 L/m2; the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel.
The pharmacokinetic data of 260 mg/m2 ABRAXANE administered over 30 minutes was compared to the pharmacokinetics of 175 mg/m2 paclitaxel injection over 3 hours. The clearance of ABRAXANE was larger (43%) than for the clearance of paclitaxel injection and the volume of distribution of ABRAXANE was also higher (53%). Differences in Cmax and Cmax corrected for dose reflected differences in total dose and rate of infusion. There were no differences in terminal half-lives.
In vitro studies of binding to human serum proteins, using paclitaxel concentrations ranging from 0.1 to 50 µg/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 a 30-minute infusion of 260 mg/m2 doses of ABRAXANE, the mean values for cumulative urinary recovery of unchanged drug (4%) indicated extensive non-renal clearance. Less than 1% of the total administered dose was excreted in urine as the metabolites 6a-hydroxypaclitaxel and 3’-p-hydroxypaclitaxel. Fecal excretion was approximately 20% of the total dose administered.
In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydroxypaclitaxel by CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4. In vitro, the metabolism of paclitaxel to 6a-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, 17a-ethinyl estradiol, retinoic acid, and quercetin, a specific inhibitor of CYP2C8, also inhibited the formation of 6a-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). The effect of renal or hepatic dysfunction on the disposition of ABRAXANE® has not been investigated.
Possible interactions of paclitaxel with concomitantly administered medications have not been formally investigated.
CLINICAL STUDIES
Metastatic Breast Carcinoma
Data from 106 patients accrued in two single arm open label studies and from 460 patients enrolled in a randomized comparative study were available to support the use of ABRAXANE in metastatic breast cancer.
INDICATION
ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) 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.
CONTRAINDICATIONS
ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1,500 cells/mm3.
WARNINGS
Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity. ABRAXANE should not be administered to patients with baseline neutrophil counts of < 1,500 cells/mm3. Frequent monitoring of blood counts should be instituted during ABRAXANE treatment. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3.
The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.
The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.
Pregnancy-Teratogenic Effects: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel protein-bound particles to rats on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the daily maximum recommended human dose on a mg/m2 basis) caused embryo- and fetotoxicity, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the daily maximum recommended human dose on a mg/m2 basis).
There are no adequate and well-controlled studies in pregnant women using ABRAXANE®. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.
There are no adequate and well-controlled studies in pregnant women using ABRAXANE®. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.
Use in Males
Men should be advised to not father a child while receiving treatment with ABRAXANE (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of effects of ABRAXANE exposure on male fertility and embryonic viability).
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
PRECAUTIONS
Drug Interactions
No drug interaction studies have been conducted with ABRAXANE.
The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering ABRAXANE (paclitaxel protein-bound particles for injectable suspension) concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4 (see CLINICAL PHARMACOLOGY).
Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (such as ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.
The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering ABRAXANE (paclitaxel protein-bound particles for injectable suspension) concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4 (see CLINICAL PHARMACOLOGY).
Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (such as ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical trials.
Hematology
ABRAXANE® therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses of therapy is recommended (see DOSAGE and ADMINISTRATION).
Nervous System
Sensory neuropathy occurs frequently with ABRAXANE. The occurrence of grade 1 or 2 sensory neuropathy does not generally require dose modification. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE (see DOSAGE and ADMINISTRATION).
Injection Site Reaction
Injection site reactions occur infrequently with ABRAXANE and were mild in the randomized clinical trial. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration.
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of ABRAXANE has not been studied.
Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.
Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1 to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS).
Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.
Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1 to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS).
Pregnancy -Teratogenic Effects: Pregnancy Category D
(See WARNINGS section).
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Following intravenous administration of carbon-14 labeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE® therapy.
Pediatric Use
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated.
Geriatric Use
Of the 229 patients in the randomized study who received ABRAXANE, 11% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among elderly patients who received ABRAXANE.
Information for Patients
(See Patient Information Leaflet).
ADVERSE REACTIONS
The following table shows the frequency of important adverse events in the randomized comparative trial for the patients who received either single-agent ABRAXANE® or paclitaxel injection for the treatment of metastatic breast cancer.
Based on worst gradeABRAXANE dose in mg/m2/duration in minutes.paclitaxel injection dose in mg/m2/duration in hours.paclitaxel injection pts received premedication.Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.Severe events are defined as at least grade 3 toxicity.During study drug dosing.
Myelosuppression and sensory neuropathy were dose related.
Based on worst gradeABRAXANE dose in mg/m2/duration in minutes.paclitaxel injection dose in mg/m2/duration in hours.paclitaxel injection pts received premedication.Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.Severe events are defined as at least grade 3 toxicity.During study drug dosing.
| Percent of Patients | ||
|---|---|---|
| ABRAXANE® 260/30 minb (n=229) | Paclitaxel Injection 175/3 hc,d (n=225) | |
| Bone Marrow | ||
| Neutropenia < 2.0 x 109/L < 0.5 x 109/L | 80 9 | 82 22 |
| Thrombocytopenia < 100 x 109/L < 50 x 109/L | 2 <1 | 3 <1 |
| Anemia < 11 g/dL < 8 g/dL | 33 1 | 25 <1 |
| Infections | 24 | 20 |
| Febrile Neutropenia | 2 | 1 |
| Bleeding | 2 | 2 |
| Hypersensitivity Reactione | ||
| All | 4 | 12 |
| Severef | 0 | 2 |
| Cardiovascular | ||
| Vital Sign Changesg | ||
| Bradycardia | <1 | <1 |
| Hypotension | 5 | 5 |
| Severe Cardiovascular Eventsf | 3 | 4 |
| Abnormal ECG | ||
| All patients | 60 | 52 |
| Patients with Normal Baseline | 35 | 30 |
| Respiratory | ||
| Cough | 7 | 6 |
| Dyspnea | 12 | 9 |
| Sensory Neuropathy | ||
| Any Symptoms | 71 | 56 |
| Severe Symptomsf | 10 | 2 |
| Myalgia / Arthralgia | ||
| Any Symptoms | 44 | 49 |
| Severe Symptomsf | 8 | 4 |
| Asthenia | ||
| Any Symptoms | 47 | 39 |
| Severe Symptomsf | 8 | 3 |
| Fluid Retention/Edema | ||
| Any Symptoms | 10 | 8 |
| Severe Symptomsf | 0 | <1 |
| Gastrointestinal | ||
| Nausea | ||
| Any symptoms | 30 | 22 |
| Severe symptomsf | 3 | <1 |
| Vomiting | ||
| Any symptoms | 18 | 10 |
| Severe Symptomsf | 4 | 1 |
| Diarrhea | ||
| Any Symptoms | 27 | 15 |
| Severe Symptomsf | <1 | 1 |
| Mucositis | ||
| Any Symptoms | 7 | 6 |
| Severe Symptomsf | <1 | 0 |
| Alopecia | 90 | 94 |
| Hepatic (Patients with Normal Baseline) | ||
| Bilirubin Elevations | 7 | 7 |
| Alkaline Phosphatase Elevations | 36 | 31 |
| AST (SGOT) Elevations | 39 | 32 |
| Injection Site Reaction | <1 | 1 |
Adverse Event Experiences by Body System
Unless otherwise noted, the following discussion refers to the primary safety database of 229 patients with metastatic breast cancer treated with single-agent ABRAXANE® in the randomized controlled trial. The frequency and severity of important adverse events for the study are presented above in tabular form. In some instances, rare severe events observed with paclitaxel injection may be expected to occur with ABRAXANE.
OVERDOSAGE
There is no known antidote for ABRAXANE overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.
DOSAGE & ADMINISTRATION
After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.
Hepatic Impairment
The appropriate dose of ABRAXANE for patients with bilirubin greater than 1.5 mg/dL is not known.
Dose Reduction
Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m2 for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m2. For grade 3 sensory neuropathy hold treatment until resolution to grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE.
Preparation and Adminstration Precautions
ABRAXANE is a cytotoxic anticancer drug and, as with other potentially toxic paclitaxel compounds, caution should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE® contacts mucous membranes, the membranes should be flushed thoroughly with water.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions (see PRECAUTIONS: Injection Site Reaction).
No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces the likelihood of infusion-related reactions (see PRECAUTIONS: Injection Site Reaction).
No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE.
Preparation for Intravenous Infusion
ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION.
Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume (mL) = Total dose (mg)/5 (mg/mL)
The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. Discard any unused portion.
Inject the appropriate amount of reconstituted ABRAXANE® into an empty, sterile IV bag (plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type IV bag). The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of an in line filter is not recommended.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
- Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, USP.
- Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF THE VIAL.
- DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized cake as this will result in foaming.
- Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting of the lyophilized cake/powder.
- Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. Avoid generation of foam.
- If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides.
Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume (mL) = Total dose (mg)/5 (mg/mL)
The reconstituted suspension should be milky and homogenous without visible particulates. If particulates or settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. Discard any unused portion.
Inject the appropriate amount of reconstituted ABRAXANE® into an empty, sterile IV bag (plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type IV bag). The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of an in line filter is not recommended.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Stability
Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20ºC to 25ºC (68ºF to 77ºF), in the original package. Neither freezing nor refrigeration adversely affects the stability of the product.
Stability of Reconstituted Suspension in the Vial
Reconstituted ABRAXANE should be used immediately, but may be refrigerated at 2ºC to 8ºC (36ºF to 46ºF) for a maximum of 8 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion.
Stability of Reconstituted Suspension in the Infusion Bag
The suspension for infusion prepared as recommended in an infusion bag should be used immediately, but may be stored at ambient temperature (approximately 25º C) and lighting conditions for up to 8 hours.
Stability of Reconstituted Suspension in the Vial
Reconstituted ABRAXANE should be used immediately, but may be refrigerated at 2ºC to 8ºC (36ºF to 46ºF) for a maximum of 8 hours if necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the original carton to protect it from bright light. Discard any unused portion.
Stability of Reconstituted Suspension in the Infusion Bag
The suspension for infusion prepared as recommended in an infusion bag should be used immediately, but may be stored at ambient temperature (approximately 25º C) and lighting conditions for up to 8 hours.
HOW SUPPLIED
Product No. 103450
NDC No. 68817-134-50 100 mg of paclitaxel in a single use vial, individually packaged in a carton.
NDC No. 68817-134-50 100 mg of paclitaxel in a single use vial, individually packaged in a carton.
Storage
Store the vials in original cartons at 20º C to 25º C (68º F to 77ºF). Retain in the original package to protect from bright light.
Handling and Disposal
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
U.S. Patent Numbers: 5,439,686; 5,498,421; 6,096,331; 6,506,405;
6,537,579; 6,749,868; 6,753,006
6,537,579; 6,749,868; 6,753,006
REFERENCES
- Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Publication No. 83-2621. For sale by the Superintendent of Documents, US Government NIH Printing Office, Washington, DC 20402.
- AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA, 1985; 253(11):1590-1592.
- National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents. Available from Louis R Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences. 179 Longwood Avenue, Boston, Massachusetts 02115.
- Clinical Oncological Society of Australia. Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.
- Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians, 1983; (Sept/Oct) 258-263.
- American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm, 1990; 47:1033-1049.
- Controlling Occupational Exposure to Hazardous Drugs. (OSHA WORK-PRACTICE GUIDELINES.) Am J Health-Syst Pharm, 1996; 53:1669-1686.
- ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice Pittsburgh, Pa: Oncology Nursing Society; 1999:32-41.
ABRAXIS ONCOLOGY
A Division of Abraxis BioScience, Inc.
Los Angeles, CA 90049
A Division of Abraxis BioScience, Inc.
Los Angeles, CA 90049
PATIENT INFORMATION
ABRAXANE® for Injectable Suspension
[generic name = (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)]
[generic name = (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)]
WHAT IS ABRAXANE?
ABRAXANE is a prescription cancer medicine. It is injected into a vein and it is used to treat advanced breast cancer.
WHAT IS CANCER?
Under normal conditions, the cells in your body divide and grow in an orderly, controlled way. Cell division and growth are necessary for the human body to perform its functions and to repair itself, when necessary. Cancer cells are different from normal cells because they are not able to control their own growth. The reasons for this abnormal growth are not yet fully understood. A tumor is a mass of unhealthy cells that are dividing and growing fast and in an uncontrolled way. When a tumor invades surrounding healthy body tissue it is known as a malignant tumor. A malignant tumor can spread (metastasize) from its original site to other parts of the body if not found and treated early.
HOW DOES ABRAXANE WORK?
ABRAXANE is a type of medical treatment called chemotherapy. The purpose of chemotherapy is to kill cancer cells or prevent their growth.
All cells, whether they are healthy cells or cancer cells, go through several stages of growth. During one of the stages, the cell starts to divide. ABRAXANE may stop the cells from dividing and growing, so they eventually die. In addition, normal cells may also be affected by ABRAXANE causing some of the side effects. (see WHAT ARE THE POSSIBLE SIDE EFFECTS OF ABRAXANE? below).
All cells, whether they are healthy cells or cancer cells, go through several stages of growth. During one of the stages, the cell starts to divide. ABRAXANE may stop the cells from dividing and growing, so they eventually die. In addition, normal cells may also be affected by ABRAXANE causing some of the side effects. (see WHAT ARE THE POSSIBLE SIDE EFFECTS OF ABRAXANE? below).
WHO SHOULD NOT TAKE ABRAXANE?
ABRAXANE should not be given to patients with dangerously low white blood cell counts.
HOW IS ABRAXANE® GIVEN?
ABRAXANE is injected into a vein [intravenous (I.V.) infusion] over 30 minutes.
WHAT PREMEDICATION IS REQUIRED WITH ABRAXANE?
While reactions can occur to any medication, severe allergic reactions to ABRAXANE are uncommon and premedication is not required. However, you should make your doctor aware of any allergies you may have so he/she can determine the course of action required.
WHAT ARE THE POSSIBLE SIDE EFFECTS OF ABRAXANE?
Most patients taking ABRAXANE will experience side effects, although it is not always possible to tell whether such effects are caused by ABRAXANE, another medicine they may be taking, or the cancer itself. Important side effects are described below; however, some patients may experience other side effects that are less common. Report any unusual symptoms to your doctor.
Important side effects observed in studies of patients taking ABRAXANE were as follows:
Hair Loss: Complete hair loss, or alopecia, almost always occurs with ABRAXANE. This usually involves the loss of eyebrows, eyelashes, and pubic hair, as well as scalp hair. It can occur suddenly after treatment has begun, but usually happens 14 to 21 days after treatment. Hair generally grows back after you’ve finished your ABRAXANE treatment.
Infections Due to Low White Blood Cell Count: Among the body’s defenses against bacterial infections are white blood cells. Between your ABRAXANE treatment cycles, you will often have blood tests to check your white blood cell counts. ABRAXANE usually causes a brief drop in white blood cells. If you have a fever (temperature above 100.4°F) or other sign of infection, tell your doctor right away. Sometimes serious infections develop that require treatment in the hospital with antibiotics. Serious illness or death could result if such infections are not treated when white blood cell counts are low.
Numbness, Tingling, or Burning in the Hands and/or Feet (Neuropathy): These symptoms occur often with ABRAXANE® and usually get better or go away without medication within three weeks of interrupting treatment. Be sure to tell your doctor about any numbness, tingling or burning that you have in your hands or feet so that he/she can decide the best approach for relief of your symptoms. Sometimes it is necessary to interrupt treatment with ABRAXANE until these symptoms improve. After improvement, treatment can be restarted at a lower dose.
Fatigue and Weakness: ABRAXANE may cause asthenia, fatigue, weakness, lethargy and malaise. These side effects are usually self-limited and do not require dose modification or interruption.
Low Red Blood Cell Count: Red blood cells deliver oxygen to tissues throughout all parts of the body and take carbon dioxide from the tissues by using a protein called hemoglobin. A lowering of the volume of red blood cells may occur following ABRAXANE treatment causing anemia. Some patients may need a blood transfusion to treat the anemia. Patients can feel tired, tire easily, appear pale, and become short of breath. Contact your doctor if you experience any of these symptoms following ABRAXANE treatment.
Mouth or Lip Sores (Mucositis): Some patients develop redness and/or sores in the mouth or on the lips. These symptoms might occur a few days after the ABRAXANE treatment and usually decrease or disappear within one week. Talk with your doctor about proper mouth care and other ways to prevent or reduce your chances of developing mucositis.
Joint and Muscle Pain: You may get joint and muscle pain a few days after your ABRAXANE treatment. These symptoms usually disappear in a few days. Although pain medicine may not be necessary, tell your doctor if you are uncomfortable.
Stomach Upset and Diarrhea: Some patients experience nausea, vomiting, and/or diarrhea following ABRAXANE use. If you experience nausea or stomach upset, tell your doctor because medicines can be given that almost always reduce or eliminate these symptoms. Diarrhea will usually disappear without treatment; however, if you experience severe abdominal or stomach area pain and/or severe diarrhea, tell your doctor right away.
Heart and Blood Vessel (Cardiovascular) Effects: ABRAXANE® may cause a drop in heart rate (bradycardia) and low blood pressure (hypotension). The patient usually does not notice these changes. These changes usually do not require treatment. You should notify your doctor if you have a history of heart disease.
Irritation at the Injection Site: ABRAXANE may cause irritation at the site where it enters the vein. Reactions may include discomfort, redness, swelling, inflammation (of the surrounding skin or of the vein itself), and ulceration (open sores). These reactions are usually caused by the I.V. (intravenous) fluid leaking into the surrounding area. If you notice anything unusual at the site of the injection (needle), either during or after treatment, tell your doctor right away.
Talk with your doctor or other healthcare professional to discuss ways to prevent or reduce some of these side effects. Because this leaflet does not include all possible side effects that can occur with ABRAXANE, it is important to talk with your doctor about other possible side effects.
Important side effects observed in studies of patients taking ABRAXANE were as follows:
Hair Loss: Complete hair loss, or alopecia, almost always occurs with ABRAXANE. This usually involves the loss of eyebrows, eyelashes, and pubic hair, as well as scalp hair. It can occur suddenly after treatment has begun, but usually happens 14 to 21 days after treatment. Hair generally grows back after you’ve finished your ABRAXANE treatment.
Infections Due to Low White Blood Cell Count: Among the body’s defenses against bacterial infections are white blood cells. Between your ABRAXANE treatment cycles, you will often have blood tests to check your white blood cell counts. ABRAXANE usually causes a brief drop in white blood cells. If you have a fever (temperature above 100.4°F) or other sign of infection, tell your doctor right away. Sometimes serious infections develop that require treatment in the hospital with antibiotics. Serious illness or death could result if such infections are not treated when white blood cell counts are low.
Numbness, Tingling, or Burning in the Hands and/or Feet (Neuropathy): These symptoms occur often with ABRAXANE® and usually get better or go away without medication within three weeks of interrupting treatment. Be sure to tell your doctor about any numbness, tingling or burning that you have in your hands or feet so that he/she can decide the best approach for relief of your symptoms. Sometimes it is necessary to interrupt treatment with ABRAXANE until these symptoms improve. After improvement, treatment can be restarted at a lower dose.
Fatigue and Weakness: ABRAXANE may cause asthenia, fatigue, weakness, lethargy and malaise. These side effects are usually self-limited and do not require dose modification or interruption.
Low Red Blood Cell Count: Red blood cells deliver oxygen to tissues throughout all parts of the body and take carbon dioxide from the tissues by using a protein called hemoglobin. A lowering of the volume of red blood cells may occur following ABRAXANE treatment causing anemia. Some patients may need a blood transfusion to treat the anemia. Patients can feel tired, tire easily, appear pale, and become short of breath. Contact your doctor if you experience any of these symptoms following ABRAXANE treatment.
Mouth or Lip Sores (Mucositis): Some patients develop redness and/or sores in the mouth or on the lips. These symptoms might occur a few days after the ABRAXANE treatment and usually decrease or disappear within one week. Talk with your doctor about proper mouth care and other ways to prevent or reduce your chances of developing mucositis.
Joint and Muscle Pain: You may get joint and muscle pain a few days after your ABRAXANE treatment. These symptoms usually disappear in a few days. Although pain medicine may not be necessary, tell your doctor if you are uncomfortable.
Stomach Upset and Diarrhea: Some patients experience nausea, vomiting, and/or diarrhea following ABRAXANE use. If you experience nausea or stomach upset, tell your doctor because medicines can be given that almost always reduce or eliminate these symptoms. Diarrhea will usually disappear without treatment; however, if you experience severe abdominal or stomach area pain and/or severe diarrhea, tell your doctor right away.
Heart and Blood Vessel (Cardiovascular) Effects: ABRAXANE® may cause a drop in heart rate (bradycardia) and low blood pressure (hypotension). The patient usually does not notice these changes. These changes usually do not require treatment. You should notify your doctor if you have a history of heart disease.
Irritation at the Injection Site: ABRAXANE may cause irritation at the site where it enters the vein. Reactions may include discomfort, redness, swelling, inflammation (of the surrounding skin or of the vein itself), and ulceration (open sores). These reactions are usually caused by the I.V. (intravenous) fluid leaking into the surrounding area. If you notice anything unusual at the site of the injection (needle), either during or after treatment, tell your doctor right away.
Talk with your doctor or other healthcare professional to discuss ways to prevent or reduce some of these side effects. Because this leaflet does not include all possible side effects that can occur with ABRAXANE, it is important to talk with your doctor about other possible side effects.
CAN I TAKE ABRAXANE IF I AM PREGNANT OR NURSING A BABY?
ABRAXANE could harm the fetus when given to a pregnant woman. Women should avoid becoming pregnant while they are undergoing treatment with ABRAXANE. Tell your doctor if you become pregnant or plan to become pregnant while taking ABRAXANE.
Men should be advised not to father a child while receiving treatment with ABRAXANE.
Because studies have shown the active agent (paclitaxel) in ABRAXANE to be present in the breast milk of animals receiving the active agent, it may be present in human breast milk as well. Therefore, nursing a baby while taking ABRAXANE is NOT recommended. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE therapy.
This medicine was prescribed for your particular condition. This summary does not include everything there is to know about ABRAXANE®. Medicines are sometimes prescribed for purposes other than those uled in a Patient Information Leaflet. If you have questions or concerns, or want more information about ABRAXANE, your doctor and pharmacist have the complete prescribing information upon which this guide is based. You may want to read it and discuss it with your doctor. Remember, no written summary can replace careful discussion with your doctor.
Men should be advised not to father a child while receiving treatment with ABRAXANE.
Because studies have shown the active agent (paclitaxel) in ABRAXANE to be present in the breast milk of animals receiving the active agent, it may be present in human breast milk as well. Therefore, nursing a baby while taking ABRAXANE is NOT recommended. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE therapy.
This medicine was prescribed for your particular condition. This summary does not include everything there is to know about ABRAXANE®. Medicines are sometimes prescribed for purposes other than those uled in a Patient Information Leaflet. If you have questions or concerns, or want more information about ABRAXANE, your doctor and pharmacist have the complete prescribing information upon which this guide is based. You may want to read it and discuss it with your doctor. Remember, no written summary can replace careful discussion with your doctor.
