DESCRIPTION

Vectibix (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Panitumumab has an approximate molecular weight of 147 kDa. Panitumumab is produced in genetically engineered mammalian (Chinese hamster ovary) cells.

Vectibix is a sterile, colorless, pH 5.6 to 6.0 liquid for intravenous (IV) infusion, which may contain a small amount of visible translucent-to-white, amorphous, proteinaceous, panitumumab particulates. Each single-use 5 mL vial contains 100 mg of panitumumab, 29 mg sodium chloride, 34 mg sodium acetate, and Water for Injection, USP. Each single-use 10 mL vial contains 200 mg of panitumumab, 58 mg sodium chloride, 68 mg sodium acetate, and Water for Injection, USP. Each single-use 20 mL vial contains 400 mg of panitumumab, 117 mg sodium chloride, 136 mg sodium acetate, and Water for Injection, USP.

DOSAGE AND ADMINISTRATION

Patient Selection

Prior to initiation of treatment with Vectibix, assess KRAS mutational status in colorectal tumors and confirm the absence of a KRAS mutation using an FDA-approved test [see WARNINGS AND PRECAUTIONS]. Information on FDA-approved tests for the detection of KRAS mutations in patients with metastatic colorectal cancer is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dose

The recommended dose of Vectibix is 6 mg/kg, administered as an intravenous infusion over 60 minutes, every 14 days. If the first infusion is tolerated, administer subsequent infusions over 30 to 60 minutes. Administer doses higher than 1000 mg over 90 minutes [see Preparation and Administration].

Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions [see WARNINGS AND PRECAUTIONS].

Dose Modifications

Dose Modifications for Infusion Reactions

[see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS]

• Reduce infusion rate by 50% in patients experiencing a mild or moderate (grade 1 or 2) infusion reaction for the duration of that infusion.
• Terminate the infusion in patients experiencing severe infusion reactions. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix.

Dose Modifications for Dermatologic Toxicity

[see BOXED WARNING, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS]

• Upon first occurrence of a grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < grade 3, reinitiate Vectibix at the original dose.
• Upon the second occurrence of a grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < grade 3, reinitiate Vectibix at 80% of the original dose.
• Upon the third occurrence of a grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < grade 3, reinitiate Vectibix at 60% of the original dose.
• Upon the fourth occurrence of a grade 3 (NCI-CTC/CTCAE) dermatologic reaction, permanently discontinue Vectibix.

Permanently discontinue Vectibix following the occurrence of a grade 4 dermatologic reaction or for a grade 3 (NCI-CTC/CTCAE) dermatologic reaction that does not recover after withholding 1 or 2 doses.

Preparation And Administration

Do not administer Vectibix as an intravenous push or bolus.

Preparation

Prepare the solution for infusion, using aseptic technique, as follows:

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Although Vectibix should be colorless, the solution may contain a small amount of visible translucent-to-white, amorphous, proteinaceous, panitumumab particulates (which will be removed by filtration; see below). Do not shake. Do not administer Vectibix if discoloration is observed.
• Withdraw the necessary amount of Vectibix for a dose of 6 mg/kg.
• Dilute to a total volume of 100 mL with 0.9% sodium chloride injection, USP. Doses higher than 1000 mg should be diluted to 150 mL with 0.9% sodium chloride injection, USP. Do not exceed a final concentration of 10 mg/mL.
• Mix diluted solution by gentle inversion. Do not shake.

Administration

• Administer using a low-protein-binding 0.2 μm or 0.22 μm in-line filter.
• Vectibix must be administered via infusion pump.
  • Flush line before and after Vectibix administration with 0.9% sodium chloride injection, USP, to avoid mixing with other drug products or intravenous solutions. Do not mix Vectibix with, or administer as an infusion with, other medicinal products. Do not add other medications to solutions containing panitumumab.
  • Infuse doses of 1000 mg or lower over 60 minutes through a peripheral intravenous line or indwelling intravenous catheter. If the first infusion is tolerated, administer subsequent infusions over 30 to 60 minutes. Administer doses higher than 1000 mg over 90 minutes.
• Use the diluted infusion solution of Vectibix within 6 hours of preparation if stored at room temperature, or within 24 hours of dilution if stored at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

• Discard any unused portion remaining in the vial.

HOW SUPPLIED

Dosage Forms And Strengths

100 mg panitumumab in 5 mL (20 mg/mL) single-use vial.

200 mg panitumumab in 10 mL (20 mg/mL) single-use vial.

400 mg panitumumab in 20 mL (20 mg/mL) single-use vial.

Storage And Handling

Vectibix is supplied as a sterile, colorless, preservative-free solution containing 20 mg/mL Vectibix (panitumumab) in a single-use vial.

Vectibix is provided as one vial per carton.

Each 5 mL single-use vial contains 100 mg of panitumumab in 5 mL (20 mg/mL) (NDC 55513-954-01).

Each 10 mL single-use vial contains 200 mg of panitumumab in 10 mL (20 mg/mL) (NDC 55513-955-01).

Each 20 mL single-use vial contains 400 mg of panitumumab in 20 mL (20 mg/mL) (NDC 55513-956-01).

Store vials in the original carton under refrigeration at 2° to 8°C (36° to 46°F) until time of use. Protect from direct sunlight. DO NOT FREEZE. Since Vectibix does not contain preservatives, any unused portion remaining in the vial must be discarded.

The diluted infusion solution of Vectibix should be used within 6 hours of preparation if stored at room temperature, or within 24 hours of dilution if stored at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

• Dermatologic and Soft Tissue Toxicity [see BOXED WARNING, DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Increased Tumor Progression, Increased Mortality, or Lack of Benefit in KRAS-Mutant mCRC [see INDICATIONS AND USAGE and WARNINGS AND PRECAUTIONS]
• Electrolyte Depletion/Monitoring [see WARNINGS AND PRECAUTIONS]
• Infusion Reactions [see DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Acute Renal Failure in Combination with Chemotherapy [see WARNINGS AND PRECAUTIONS]
• Pulmonary Fibrosis/Interstitial Lung Disease (ILD) [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]
• Ocular Toxicities [see WARNINGS AND PRECAUTIONS]
• Increased Mortality and Toxicity with Vectibix in combination with Bevacizumab and Chemotherapy [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Safety data are presented from two clinical trials in which patients received Vectibix: Study 1, an open-label, multinational, randomized, controlled, monotherapy clinical trial (N = 463) evaluating Vectibix with best supportive care (BSC) versus BSC alone in patients with EGFR-expressing mCRC and Study 3, a randomized, controlled trial (N = 1183) in patients with mCRC that evaluated Vectibix in combination with FOLFOX chemotherapy versus FOLFOX chemotherapy alone. Safety data for Study 3 are limited to 656 patients with wild-type KRAS mCRC.