Dosage & Administration
Abraxane Prescribing Information
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- Do not administer ABRAXANE therapy to patients with baseline neutrophil counts of less than 1,500 cells/mm3 [see Contraindications (4)].
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- Monitor for neutropenia, which may be severe and result in infection or sepsis [see Warnings and Precautions (5.1, 5.3)].
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- Perform frequent complete blood cell counts on all patients receiving ABRAXANE [see Warnings and Precautions (5.1, 5.3)].
Metastatic Breast Cancer
ABRAXANE 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.
Non-Small Cell Lung Cancer
ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
Adenocarcinoma of the Pancreas
ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.
Important Administration Instructions
DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. ABRAXANE has different dosage and administration instructions from other paclitaxel products.
Closely monitor the infusion site for extravasation or drug infiltration during administration. Limiting the infusion of ABRAXANE to 30 minutes may reduce the risk of infusion-related reactions [see Adverse Reactions (6.2)].
Consider premedication in patients who have had prior hypersensitivity reactions to ABRAXANE. Do not re-challenge patients who experience a severe hypersensitivity reaction to ABRAXANE [see Contraindications (4) and Warnings and Precautions (5.5)].
Recommended Dosage for Metastatic Breast Cancer
After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.
Recommended Dosage for Non-Small Cell Lung Cancer
The recommended dose of ABRAXANE is 100 mg/m2 administered as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. Administer carboplatin on Day 1 of each 21-day cycle immediately after ABRAXANE [see Clinical Studies (14.2)].
Recommended Dosage for Adenocarcinoma of the Pancreas
The recommended dose of ABRAXANE is 125 mg/m2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer gemcitabine immediately after ABRAXANE on Days 1, 8, and 15 of each 28-day cycle [see Clinical Studies (14.3)].
Dosage Modifications for Hepatic Impairment
For patients with moderate or severe hepatic impairment, reduce the starting dose of ABRAXANE as shown in Table 1.
| AST = Aspartate Aminotransferase; MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer; ULN = Upper limit of normal. a Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. b A dose increase to 260 mg/m2 for patients with metastatic breast cancer or 100 mg/m2 for patients with non-small cell lung cancer in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles. c Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer. | ||||||
AST Levels | Bilirubin Levels | ABRAXANE Dosea | ||||
MBC | NSCLC c | Adenocarcinoma | ||||
Moderate | < 10 x ULN | AND | > 1.5 to ≤ 3 x ULN | 200 mg/m2 b | 80 mg/m2 b | not recommended |
Severe | < 10 x ULN | AND | > 3 to ≤ 5 x ULN | 200 mg/m2 b | 80 mg/m2 b | not recommended |
> 10 x ULN | OR | > 5 x ULN | not recommended | not recommended | not recommended | |
Dosage Modifications for Adverse Reactions
Metastatic Breast Cancer
Patients who experience severe neutropenia (neutrophils less than 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 [see Contraindications (4), Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6.1)].
Non-Small Cell Lung Cancer
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- Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3 [see Contraindications (4), Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
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- In patients who develop severe neutropenia or thrombocytopenia withhold treatment until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil count of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce ABRAXANE and carboplatin doses as outlined in Table 2.
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- Withhold ABRAXANE for Grade 3-4 peripheral neuropathy. Resume ABRAXANE and carboplatin at reduced doses (see Table 2) when peripheral neuropathy improves to Grade 1 or completely resolves [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].
Adverse Reaction | Occurrence | Weekly | Every 3-Week |
Neutropenic Fever (ANC less than 500/mm3 with fever >38°C) | First | 75 | 4.5 |
Second | 50 | 3 | |
Third | Discontinue Treatment | ||
Platelet count less than 50,000/mm3 | First | 75 | 4.5 |
Second | Discontinue Treatment | ||
Severe sensory Neuropathy – Grade 3 or 4 | First | 75 | 4.5 |
Second | 50 | 3 | |
Third | Discontinue Treatment | ||
Adenocarcinoma of the Pancreas
Dose level reductions for patients with adenocarcinoma of the pancreas, as referenced in Tables 4 and 5, are provided in Table 3.
Dose Level | ABRAXANE (mg/m2) | Gemcitabine (mg/m2) |
Full dose | 125 | 1000 |
1st dose reduction | 100 | 800 |
2nd dose reduction | 75 | 600 |
If additional dose reduction required | Discontinue | Discontinue |
Recommended dose modifications for neutropenia and thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in Table 4.
| ANC = Absolute Neutrophil Count | ||||
Cycle | ANC (cells/mm3) |
| Platelet count (cells/mm3) | ABRAXANE / Gemcitabine |
Day 1 | < 1500 | OR | < 100,000 | Delay doses until recovery |
Day 8 | 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level |
| < 500 | OR | < 50,000 | Withhold doses |
Day 15: If Day 8 doses were reduced or given without modification: | ||||
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 1 dose level from Day 8 |
| < 500 | OR | < 50,000 | Withhold doses |
Day 15: If Day 8 doses were withheld: | ||||
| ≥ 1000 | OR | ≥ 75,000 | Reduce 1 dose level from Day 1 |
| 500 to < 1000 | OR | 50,000 to < 75,000 | Reduce 2 dose levels from Day 1 |
| < 500 | OR | < 50,000 | Withhold doses |
Recommended dose modifications for other adverse reactions in patients with adenocarcinoma of the pancreas are provided in Table 5.
Adverse Reaction | ABRAXANE | Gemcitabine |
Febrile Neutropenia: | Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose level | |
Peripheral Neuropathy: | Withhold until improves to ≤ Grade 1; | No dose reduction |
Cutaneous Toxicity: | Reduce to next lower dose level; discontinue treatment if toxicity persists | |
Gastrointestinal Toxicity: | Withhold until improves to ≤ Grade 1; | |
Preparation for Intravenous Administration
ABRAXANE is a cytotoxic drug. Follow applicable special handling and disposal procedures.1 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.
ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use.
Read the entire preparation instructions prior to reconstitution.
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Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.
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.
Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient and slowly withdraw the dosing volume of the reconstituted suspension from the vial(s) into a syringe: Dosing volume (mL)=Total dose (mg)/5 (mg/mL).
Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile intravenous bag [plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type intravenous bag]. The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or administer ABRAXANE infusions. The use of medical devices containing silicone oil as a lubricant (i.e., syringes and intravenous bags) to reconstitute and administer ABRAXANE may result in the formation of proteinaceous strands.
Visually inspect the reconstituted ABRAXANE suspension in the intravenous bag prior to administration. Discard the reconstituted suspension if proteinaceous strands, particulate matter, or discoloration are observed.
Stability
Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between 20°C to 25°C (68°F to 77°F) in the original package. Neither freezing nor refrigeration adversely affects the stability of the product.
Stability of Reconstituted Suspension in the Vial
Reconstituted ABRAXANE in the vial should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 24 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 when prepared as recommended in an infusion bag should be used immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from bright light for a maximum of 24 hours.
The total combined refrigerated storage time of reconstituted ABRAXANE in the vial and in the infusion bag is 24 hours. This may be followed by storage in the infusion bag at ambient temperature (approximately 25°C) and lighting conditions for a maximum of 4 hours.
Discard any unused portion.
For injectable suspension, for intravenous use: white to yellow, sterile lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-dose vial for reconstitution.
Pregnancy
Risk Summary
Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available human data on ABRAXANE use in pregnant women to inform the drug-associated risk.
In animal reproduction studies, administration of paclitaxel formulated as albumin-bound particles to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at doses approximately 2% of the daily maximum recommended human dose on a mg/m2 basis (see Data). Advise females of reproductive potential of the potential risk to a fetus.
The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In embryo-fetal development studies, intravenous administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, 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-fetal toxicities, 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.
Lactation
Risk Summary
There are no data on the presence of paclitaxel in human milk, or its effect on the breastfed child or on milk production. In animal studies, paclitaxel and/or its metabolites were excreted into the milk of lactating rats (see Data). Because of the potential for serious adverse reactions in a breastfed child from ABRAXANE, advise lactating women not to breastfeed during treatment with ABRAXANE and for two weeks after the last dose.
Data
Animal Data
Following intravenous administration of radiolabeled 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.
Females and Males of Reproductive Potential
Based on animal studies and mechanism of action, ABRAXANE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to starting treatment with ABRAXANE.
Contraception
Females
Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE.
Males
Based on findings in genetic toxicity and animal reproduction studies, advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1)].
Infertility
Females and Males
Based on findings in animals, ABRAXANE may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)].
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Pharmacokinetics, safety, and antitumor activity of ABRAXANE were assessed in an open-label, dose escalation, dose expansion study (NCT01962103) in 96 pediatric patients aged 1.4 to < 17 years with recurrent or refractory pediatric solid tumors. The maximum tolerated dose (MTD) normalized for body surface area (BSA) was lower in pediatric patients compared to adults. No new safety signals were observed in pediatric patients across these studies.
Paclitaxel protein-bound exposures normalized by dose were higher in 96 pediatric patients (aged 1.4 to < 17 years) as compared to those in adults.
Geriatric Use
Of the 229 patients in the randomized study who received ABRAXANE for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. This study of ABRAXANE did not include a sufficient number of patients with metastatic breast cancer who were 65 years and older to determine whether they respond differently from younger patients.
A subsequent pooled analysis was conducted in 981 patients receiving ABRAXANE monotherapy for metastatic breast cancer, of which 15% were 65 years of age or older and 2% were 75 years of age or older. A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years of age or older.
Of the 514 patients in the randomized study who received ABRAXANE and carboplatin for the first-line treatment of non-small cell lung cancer, 31% were 65 years or older and 3.5% were 75 years or older. Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients 65 years or older compared to patients younger than 65 years old. No overall difference in effectiveness, as measured by response rates, was observed between patients 65 years or older compared to patients younger than 65 years old.
Of the 431 patients in the randomized study who received ABRAXANE and gemcitabine for the first-line treatment of pancreatic adenocarcinoma, 41% were 65 years or older and 10% were 75 years or older. No overall differences in effectiveness were observed between patients who were 65 years of age or older and younger patients. Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old. Clinical studies of ABRAXANE did not include sufficient number of patients with pancreatic cancer who were 75 years and older to determine whether they respond differently from younger patients.
Renal Impairment
No adjustment of the starting ABRAXANE dose is required for patients with mild to moderate renal impairment (estimated creatinine clearance 30 to <90 mL/min) [see Clinical Pharmacology (12.3)]. There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min).
Hepatic Impairment
No adjustment of the starting ABRAXANE dose is required for patients with mild hepatic impairment (total bilirubin > ULN and ≤ 1.5 x ULN and aspartate aminotransferase [AST] ≤ 10 x ULN). Reduce ABRAXANE starting dose in patients with moderate to severe hepatic impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)]. ABRAXANE is not recommended for use in patients with total bilirubin > 5 x ULN or AST > 10 x ULN [see Dosage and Administration (2.5), Warnings and Precautions (5.6), and Clinical Pharmacology (12.3)]. ABRAXANE is not recommended for use in patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment [see Dosage and Administration (2.5)].
ABRAXANE is contraindicated in patients with:
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- Baseline neutrophil counts of < 1,500 cells/mm3[see Warnings and Precautions (5.1)]
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- A history of severe hypersensitivity reactions to ABRAXANE [see Warnings and Precautions (5.5)]