Panitumumab - Vectibix®
|The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.|
Preparation and Administration
|Stability / Miscellaneous|
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.
Mechanism of Action
Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and internalization of the EGFR. In vitro assays and in vivo animal studies demonstrate that panitumumab inhibits the growth and survival of selected human tumor cell lines expressing EGFR.
1. INDICATIONS AND USAGE
The effectiveness of Vectibix as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma is based on progression-free survival [see PACKAGE INSERT FOR Clinical Studies (14)]. Currently, no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations [see PACKAGE INSERT FOR Clinical Studies (14) and Clinical Pharmacology (12.1)].
2.1 Recommended Dose and Dose Modifications
Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions.
Dose Modifications for Infusion Reactions[see Boxed Warning, PACKAGE INSERT FOR Warnings and Precautions (5.2), and Adverse Reactions (6.1, 6.3)] 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
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
Discard any unused portion remaining in the vial.
3. DOSAGE FORMS AND STRENGTHS
200 mg of panitumumab in 10 mL (20 mg/mL) single-use vial.
400 mg of panitumumab in 20 mL (20 mg/mL) single-use vial.
5. WARNINGS AND PRECAUTIONS
5.1 Dermatologic Toxicity
5.2 Infusion Reactions
Infusion reactions, manifesting as anaphylactoid reactions, bronchospasm, and hypotension, can occur following Vectibix administration [see Boxed Warning, and Adverse Reactions (6.1, 6.3)]. In clinical studies, severe infusion reactions occurred with the administration of Vectibix in approximately 1% of patients. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions [see Dosage and Administration (2.1)].
5.3 Increased Toxicity With Combination Chemotherapy
As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study, compared with those randomized to bevacizumab and chemotherapy.
In a single-arm study of 19 patients receiving Vectibix in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in one patient. In a single-arm study of 24 patients receiving Vectibix plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.
Severe diarrhea and dehydration, which may lead to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
5.4 Pulmonary Fibrosis
One case occurred in a patient with underlying idiopathic pulmonary fibrosis who received Vectibix in combination with chemotherapy and resulted in death from worsening pulmonary fibrosis after four doses of Vectibix. The second case was characterized by cough and wheezing 8 days following the initial dose, exertional dyspnea on the day of the seventh dose, and persistent symptoms and CT evidence of pulmonary fibrosis following the 11th dose of Vectibix as monotherapy. An additional patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia after 23 doses of Vectibix in combination with chemotherapy. Permanently discontinue Vectibix therapy in patients developing interstitial lung disease, pneumonitis, or lung infiltrates.
5.5 Electrolyte Depletion/Monitoring
5.7 EGF Receptor Testing
Assessment for EGFR expression should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specific reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation can lead to unreliable results. Refer to the package insert for the Dako EGFR pharmDx® test kit, or other test kits approved by FDA, for identification of patients eligible for treatment with Vectibix and for full instructions on assay performance.
HOW SUPPLIED/STORAGE AND HANDLING
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).
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
This product, its production, and/or its use may be covered by one or more US Patents, including US Patent No. 6,235,883, as well as other patents or patents pending.
© 2006-2010 Amgen Inc. All rights reserved.
1) [PACKAGE INSERT DATA] : VECTIBIX® (panitumumab) solution.[AMGEN INC] One Amgen Center Drive. Thousand Oaks, CA 91320-1799. Revised: 05/2010.
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user’s use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Read the disclaimer