SIDE EFFECTS

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

• Dermatologic Toxicity [see BOXED WARNING, DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Infusion Reactions [see BOXED WARNING, DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Increased Mortality or Toxicity of Vectibix in Combination with Chemotherapy [see WARNINGS AND PRECAUTIONS]
• Pulmonary Fibrosis/ILD [see WARNINGS AND PRECAUTIONS]
• Electrolyte Depletion/Monitoring [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions 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 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. Adverse reactions requiring discontinuation of Vectibix were infusion reactions, severe skin toxicity, paronychia, and pulmonary fibrosis.

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 available from 15 clinical trials in which 1467 patients received Vectibix; of these, 1293 received Vectibix monotherapy and 174 received Vectibix in combination with chemotherapy [see WARNINGS AND PRECAUTIONS].

The data described in Table 1 and in other sections below, except where noted, reflect exposure to Vectibix administered as a single agent at the recommended dose and schedule (6 mg/kg every 2 weeks) in 229 patients with mCRC enrolled in Study 1, a randomized, controlled trial. The median number of doses was five (range: one to 26 doses), and 71% of patients received eight or fewer doses. The population had a median age of 62 years (range: 27 to 82 years), 63% were male, and 99% were white with < 1% black, < 1% Hispanic, and 0% other.

Table 1: Per-Patient Incidence of Adverse Reactions Occurring in ≥ 5% of Patients with a Between-Group Difference of ≥ 5% (Study 1)

Dermatologic, Mucosal, and Ocular Toxicity

In Study 1, dermatologic toxicities occurred in 90% of patients receiving Vectibix. Skin toxicity was severe (NCICTC grade 3 and higher) in 16% of patients. Ocular toxicities occurred in 15% of patients and included, but were not limited to, conjunctivitis (4%), ocular hyperemia (3%), increased lacrimation (2%), and eye/eyelid irritation (1%). Stomatitis (7%) and oral mucositis (6%) were reported. One patient experienced a NCI-CTC grade 3 event of mucosal inflammation. The incidence of paronychia was 25% and was severe in 2% of patients. Nail disorders occurred in 9% of patients [see WARNINGS AND PRECAUTIONS].

Median time to the development of dermatologic, nail, or ocular toxicity was 14 days after the first dose of Vectibix; the median time to most severe skin/ocular toxicity was 15 days after the first dose of Vectibix; and the median time to resolution after the last dose of Vectibix was 84 days. Severe toxicity necessitated dose interruption in 11% of Vectibix-treated patients [see DOSAGE AND ADMINISTRATION].

Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, necrotizing fasciitis, and abscesses requiring incisions and drainage were reported.

Infusion Reactions

Infusional toxicity was defined as any event within 24 hours of an infusion during the clinical study described as allergic reaction or anaphylactoid reaction, or any event occurring on the first day of dosing described as allergic reaction, anaphylactoid reaction, fever, chills, or dyspnea. Vital signs and temperature were measured within 30 minutes prior to initiation and upon completion of the Vectibix infusion. The use of premedication was not standardized in the clinical trials. Thus, the utility of premedication in preventing the first or subsequent episodes of infusional toxicity is unknown. Across several clinical trials of Vectibix monotherapy, 3% (43/1336) experienced infusion reactions of which approximately 1% (6/1336) were severe (NCI-CTC grade 3-4). In one patient, Vectibix was permanently discontinued for a serious infusion reaction [see DOSAGE AND ADMINISTRATION].

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of Vectibix has been evaluated using two different screening immunoassays for the detection of binding anti-panitumumab antibodies: an acid dissociation bridging enzyme-linked immunosorbent assay (ELISA) detecting high-affinity antibodies and a Biacore® biosensor immunoassay detecting both high- and low-affinity antibodies. For patients whose sera tested positive in screening immunoassays, an in vitro biological assay was performed to detect neutralizing antibodies.

As monotherapy: The incidence of binding antibodies (excluding pre-existing and transient positive patients) was 0.4% (3/717), as detected by the acid dissociation ELISA, and 3.8% (27/717) as detected by the Biacore® assay. The incidence of neutralizing antibodies (excluding pre-existing and transient positive patients) was 1% (7/717). There was no evidence of altered pharmacokinetic or safety profiles in patients who developed antibodies to Vectibix.

In combination with irinotecan- or oxaliplatin-based chemotherapy: The incidence of binding antibodies (excluding pre-existing positive patients) was 1% (11/1124) as detected by the acid dissociation ELISA and 0.8% (9/1123) as detected by the Biacore assay. The incidence of neutralizing antibodies (excluding pre-existing positive patients) was 0.2 % (2/1124). No evidence of an altered safety profile was found in patients who developed antibodies to Vectibix.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to panitumumab with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Vectibix. Because these reactions are reported in a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Skin and subcutaneous tissue disorders: Skin necrosis, angioedema [see BOXED WARNING, DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Immune system disorders: Anaphylactoid reaction [see BOXED WARNING, DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS]
• Eye disorders: Keratitis/ulcerative keratitis [see WARNINGS AND PRECAUTIONS]

Read the entire FDA prescribing information for Vectibix (Panitumumab Injection for Intravenous Use) »