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Included as part of the PRECAUTIONS section.

Dermatologic Toxicity

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 (panitumumab injection for intravenous use) . The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.

Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage were reported. Withhold Vectibix for severe or life-threatening dermatologic toxicity. [see BOXED WARNING, ADVERSE REACTIONS, AND DOSAGE AND ADMINISTRATION].

Infusion Reactions

In Study 1, 4% of patients experienced infusion reactions and in 1% of patients, these reactions were graded as severe (NCI-CTC grade 3–4).

Across all clinical studies, severe infusion reactions occurred with the administration of Vectibix (panitumumab injection for intravenous use) in approximately 1% of patients. Severe infusion reactions included anaphylactic reactions, bronchospasm, and hypotension [see BOXED WARNING and ADVERSE REACTIONS]. Although fatal infusion reactions have not been reported with Vectibix (panitumumab injection for intravenous use) , fatalities have occurred with other monoclonal antibody products. Stop infusion if a severe infusion reaction occurs. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix [see DOSAGE AND ADMINISTRATION].

Increased Toxicity With Combination Chemotherapy

Vectibix (panitumumab injection for intravenous use) is not indicated for use in combination with chemotherapy. In an interim analysis of Study 2, the addition of Vectibix (panitumumab injection for intravenous use) 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 [see Clinical Studies]. NCI-CTC grade 3–4 adverse drug reactions occurring at a higher rate in Vectibix (panitumumab injection for intravenous use) -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 (panitumumab injection for intravenous use) -treated patients (7% vs 4%) and included fatal events in three ( < 1%) Vectibix (panitumumab injection for intravenous use) -treated patients.

As a result of the toxicities experienced, patients randomized to Vectibix (panitumumab injection for intravenous use) , 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 (panitumumab injection for intravenous use) 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 (panitumumab injection for intravenous use) plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.

Pulmonary Fibrosis

Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix (panitumumab injection for intravenous use) . Following the initial fatality described below, patients with a history of interstitial pneumonitis, pulmonary fibrosis, evidence of interstitial pneumonitis, or pulmonary fibrosis were excluded from clinical studies. Therefore, the estimated risk in a general population that may include such patients is uncertain.

One case occurred in a patient with underlying idiopathic pulmonary fibrosis who received Vectibix (panitumumab injection for intravenous use) in combination with chemotherapy and resulted in death from worsening pulmonary fibrosis after four doses of Vectibix (panitumumab injection for intravenous use) . 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 (panitumumab injection for intravenous use) as monotherapy. An additional patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia after 23 doses of Vectibix (panitumumab injection for intravenous use) in combination with chemotherapy. Permanently discontinue Vectibix (panitumumab injection for intravenous use) therapy in patients developing interstitial lung disease, pneumonitis, or lung infiltrates.

Electrolyte Depletion/Monitoring

In Study 1, median magnesium levels decreased by 0.1 mmol/L in the Vectibix (panitumumab injection for intravenous use) arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or intravenous electrolyte repletion occurred in 2% of patients. Hypomagnesemia occurred 6 weeks or longer after the initiation of Vectibix (panitumumab injection for intravenous use) . In some patients, both hypomagnesemia and hypocalcemia occurred. Patients' electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix (panitumumab injection for intravenous use) therapy. Institute appropriate treatment, eg, oral or intravenous electrolyte repletion, as needed.

Photosensitivity

Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix (panitumumab injection for intravenous use) .

EGF Receptor Testing

Detection of EGFR protein expression is necessary for selection of patients appropriate for Vectibix (panitumumab injection for intravenous use) therapy because these are the only patients studied and for whom benefit has been shown [see INDICATIONS AND USAGE and Clinical Studies]. Patients with colorectal cancer enrolled in Study 1 were required to have immunohistochemical evidence of EGFR expression using the Dako EGFR pharmDx® test kit.

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 (panitumumab injection for intravenous use) and for full instructions on assay performance.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity or mutagenicity studies of panitumumab have been conducted. It is not known if panitumumab can impair fertility in humans. Prolonged menstrual cycles and/or amenorrhea occurred in normally cycling, female cynomolgus monkeys treated weekly with 1.25 to 5 times the recommended human dose of panitumumab (based on body weight). Menstrual cycle irregularities in panitumumab-treated female monkeys were accompanied by both a decrease and delay in peak progesterone and 17β-estradiol levels. Normal menstrual cycling resumed in most animals after discontinuation of panitumumab treatment. A no-effect level for menstrual cycle irregularities and serum hormone levels was not identified. The effects of panitumumab on male fertility have not been studied. However, no adverse effects were observed microscopically in reproductive organs from male cynomolgus monkeys treated for 26 weeks with panitumumab at doses of up to approximately 5-fold the recommended human dose (based on body weight).

Animal Toxicology and/or Pharmacology

Weekly administration of panitumumab to cynomolgus monkeys for 4 to 26 weeks resulted in dermatologic findings, including dermatitis, pustule formation and exfoliative rash, and deaths secondary to bacterial infection and sepsis at doses of 1.25 to 5-fold higher (based on body weight) than the recommended human dose.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no studies of Vectibix (panitumumab injection for intravenous use) in pregnant women. Reproduction studies in cynomolgus monkeys treated with 1.25 to 5 times the recommended human dose of panitumumab resulted in significant embryolethality and abortions; however, no other evidence of teratogenesis was noted in offspring. [see Reproductive and Developmental Toxicology]. Vectibix (panitumumab injection for intravenous use) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Based on animal models, EGFR is involved in prenatal development and may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo. Human IgG is known to cross the placental barrier; therefore, panitumumab 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 (panitumumab injection for intravenous use) 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.

Nursing Mothers

It is not known whether panitumumab is excreted into human milk; however, human IgG is excreted into human milk. Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants from Vectibix (panitumumab injection for intravenous use) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If nursing is interrupted, based on the mean half-life of panitumumab, nursing should not be resumed earlier than 2 months following the last dose of Vectibix [see CLINICAL PHARMACOLOGY].

Pediatric Use

The safety and effectiveness of Vectibix (panitumumab injection for intravenous use) have not been established in pediatric patients. The pharmacokinetic profile of Vectibix (panitumumab injection for intravenous use) has not been studied in pediatric patients.

Geriatric Use

Of 229 patients with mCRC who received Vectibix (panitumumab injection for intravenous use) in Study 1, 96 (42%) were ≥ age 65. Although the clinical study did not include a sufficient number of geriatric patients to determine whether they respond differently from younger patients, there were no apparent differences in safety and effectiveness of Vectibix (panitumumab injection for intravenous use) between these patients and younger patients.

Last reviewed on RxList: 8/5/2009
This monograph has been modified to include the generic and brand name in many instances.