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Preparation and administration1
Important considerations:
• Do not administer Vectibix® as an IV push or bolus. Vectibix® must be administered by an IV infusion pump using a low-protein-binding 0.2 µm or 0.22 µm inline filter.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. 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). Do not shake. Vectibix® should not be administered if discoloration is observed.
• Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix® infusions.
Six steps to prepare and administer Vectibix®
1. Withdraw the necessary amount of Vectibix® for a dose of 6 mg/kg.
2. Dilute to a total volume of 100 mL with 0.9% sodium chloride injection, USP.* Final concentration should not exceed 10 mg/mL.
3. Mix diluted solution by gentle inversion. DO NOT SHAKE.
4. Administer using an IV infusion pump with a low-protein-binding 0.2 µm or 0.22 µm inline filter.
5. Infuse over approximately 60 minutes through a peripheral line or indwelling catheter. Doses higher than 1,000 mg should be infused over approximately 90 minutes.
6. Flush line before and after Vectibix® administration with 0.9% sodium chloride injection, USP, to avoid mixing with other drug products or IV solutions.
* Doses higher than 1,000 mg should be diluted in 150 mL 0.9% sodium chloride injection, USP.
• If a patient develops dermatologic toxicities related to Vectibix® that are grade 3 or higher or are considered intolerable, temporarily withhold Vectibix® administration until the toxicities have improved.
• If dermatologic toxicity improves to < grade 2, and the patient is symptomatically improved after withholding no more than 2 doses of Vectibix®, treatment may be resumed at 50% of the original dose.
• If toxicities do not recur, escalate each additional dose of Vectibix® by 25% increments of the original dose until the recommended starting dose is reached.
• If toxicities do not resolve after withholding 1 or 2 doses of Vectibix®, or if toxicities recur or become intolerable at 50% of the original dose level, permanently discontinue the use of Vectibix®.
• Reduce the infusion rate by 50% in patients experiencing a mild or moderate (grade 1 or 2) infusion reaction for the duration of that infusion.
• Immediately and permanently discontinue Vectibix® infusion in patients experiencing severe (grade 3 or 4) infusion reactions.
References
1. Vectibix® (panitumumab) package insert. Amgen; 2007.
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Indication
Vectibix® (panitumumab) is indicated as a single agent for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The effectiveness of Vectibix® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. 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.
Important Safety Information, including Boxed WARNINGS
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WARNING: DERMATOLOGIC TOXICITY and INFUSION REACTIONS Dermatologic Toxicity: Dermatologic toxicities occurred in 89% of patients and were severe (NCI-CTC grade 3 or higher) in 12% of patients receiving Vectibix® monotherapy. [See Product Labeling: Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. Infusion Reactions: Severe infusion reactions occurred in approximately 1% of patients. [See Product Labeling: Warnings and Precautions (5.2) and Adverse Reactions (6.1)]. Although not reported with Vectibix®, fatal infusion reactions have occurred with other monoclonal antibody products. [See Product Labeling: Dosage and Administration (2.1)]. |
Vectibix® is not indicated for use in combination with chemotherapy. In an interim analysis of a randomized clinical trial, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/dermatitis/acneiform (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%) and hypomagnesemia (4% vs 0%). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 4%) and included fatal events in 3 (< 1%) Vectibix®-treated patients.
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 1 patient. In a single-arm study of 24 patients receiving Vectibix® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.
Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. Of the 2 cases, 1 involved a patient with underlying idiopathic pulmonary fibrosis and resulted in death. The second patient had symptoms of pulmonary fibrosis, which was confirmed by CT. Additionally, a third patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia.
In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix® arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or IV electrolyte repletion occurred in 2% of patients. Patients’ electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix® therapy.
Exposure to sunlight can exacerbate dermatologic toxicity. It is recommended that patients wear sunscreen and hats, and limit sun exposure while receiving Vectibix®.
The most common adverse events of Vectibix® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events of Vectibix® are pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.
