Vectibix^® (panitumumab) preparation and administration¹

The only FDA-approved anti-EGFR monoclonal antibody with every-other-week dosing (Q2W) schedule

Prepare infusion using appropriate aseptic technique

• 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. Final concentration should not exceed 10 mg/mL. Doses higher than 1000 mg should be diluted to 150 mL with 0.9% sodium chloride injection, USP
• Mix diluted solution by gentle inversion. DO NOT SHAKE
• Administer using an IV infusion pump with a low-protein-binding 0.2 μm or 0.22 μm in-line filter
• Infuse over approximately 60 minutes through a peripheral line or indwelling catheter. Doses higher than 1000 mg should be infused over approximately 90 minutes
• Flush line before and after Vectibix^® administration with 0.9% sodium chloride injection, USP, to avoid mixing with other drug products or IV solutions. Do not mix Vectibix^® with, or administer as an infusion with, other medicinal products. Do not add other medications to solutions containing panitumumab.
  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 degrees C (36-46 degrees F). DO NOT FREEZE.
  Discard any unused portion remaining in the vial

    No loading dose required¹

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^®.

Vectibix^® is not indicated for the treatment of patients with KRAS mutation-positive mCRC or for whom KRAS mCRC status is unknown. 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.

IMPORTANT SAFETY INFORMATION

In Study 1, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 16% of patients with mCRC receiving Vectibix^®. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix^® for the development of inflammatory or infectious sequelae. Life threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix^®. Withhold or discontinue Vectibix^® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix^® concerning dermatologic toxicity are provided in the product labeling.

Infusion reactions, manifesting as anaphylactoid reactions, bronchospasm, and hypotension, can occur following Vectibix^® administration. Terminate the infusion for severe infusion reactions.

Vectibix^® is not indicated for use in combination with chemotherapy. In a phase 3 study of patients with KRAS mutation-positive mCRC (n = 440) evaluating Vectibix^® in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared to FOLFOX alone as first-line therapy for mCRC, shortened overall survival time was observed in the mutant KRAS mCRC population after 294 deaths (HR = 1.24, 95% CI: 0.98-1.57).

In an interim analysis of Study 2, 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 three (< 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%.

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.

Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix^®. Patients with a history or evidence of interstitial pneumonitis, pulmonary fibrosis, were excluded from most clinical trials. Therefore, the estimated risk in a general population that includes such patients is uncertain. Cases of interstitial lung disease (ILD), including fatalities, have been reported in patients treated with Vectibix^®. Interrupt Vectibix^® therapy for the acute onset or worsening of pulmonary symptoms. Discontinue Vectibix^® therapy if ILD is confirmed.

In a 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. Hypomagnesemia occurred 6 weeks or longer after the initiation of Vectibix^®. In some patients, both hypomagnesemia and hypocalcemia occurred. Patients’ electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix^® therapy. Institute appropriate treatment (eg, oral or intravenous electrolyte repletion) as needed.

Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats, and limit sun exposure while receiving Vectibix^® and for 2 months after the last dose.

Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix^®. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix^® for acute or worsening keratitis.

Adequate contraception in both males and females must be used while receiving Vectibix^® and for 6 months after the last dose of Vectibix^® therapy. Vectibix^® may be transmitted from the mother to the developing fetus and has the potential to cause fetal harm when administered to pregnant women.

Women who become pregnant during Vectibix^® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1-800-772-6436 (1-800-77-AMGEN) to enroll.

Discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother. If nursing is interrupted, it should not be resumed earlier than 2 months following the last dose of Vectibix^®.

The most common adverse reactions (≥ 20%) of Vectibix^® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, diarrhea, including diarrhea resulting in dehydration, and constipation.

The most serious adverse reactions of Vectibix^® are pulmonary fibrosis, pulmonary embolism, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.

Please click here for the full Prescribing Information.

Reference: 1. Vectibix^® (panitumumab) prescribing information, Amgen.