vectibix

Important safety information

Dermatologic and Soft Tissue Toxicity: Monitor for dermatologic and soft tissue toxicities. Reduce dose for recurrent Grade 3 toxicity and withhold or discontinue Vectibix for severe or life-threatening complications. Limit sun exposure. ( 2.3 , 5.1 , 5.7 ) Increased tumor progression, increased mortality, or lack of benefit in patients with RAS -mutant mCRC, receiving Vectibix monotherapy or in combination with oxaliplatin-based chemotherapy. ( 2.1 , 5.2 ) Electrolyte Depletion/Monitoring: Monitor electrolytes and institute appropriate treatment. ( 5.3 ) Infusion Reactions: Reduce infusion rate by 50% for mild to moderate reactions; terminate the infusion for severe infusion reactions. ( 2.3 , 5.4 ) Pulmonary Fibrosis/Interstitial Lung Disease (ILD): Permanently discontinue Vectibix in patients developing ILD. ( 5.6 ) Ocular Toxicities: Monitor for keratitis, ulcerative keratitis, or corneal perforation. Interrupt or discontinue Vectibix for acute or worsening keratitis, ulcerative keratitis, or corneal perforation. ( 5.8 ) Embryo-fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception during treatment with Vectibix and for 2 months after the last dose. ( 5.10 , 8.1 , 8.3 ) 5.1 Dermatologic and Soft Tissue Toxicity Vectibix can cause dermatologic toxicity, which may be severe. Clinical manifestations included, but were not limited to, acneiform dermatitis, pruritis, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Among 229 patients who received Vectibix as monotherapy, dermatologic toxicity occurred in 90% including Grade 3 (15%). Among 585 patients who received Vectibix in combination with FOLFOX, dermatologic toxicity occurred in 96% including Grade 4 (1%) and Grade 3 (32%). In 126 patients receiving Vectibix in combination with sotorasib across clinical studies, dermatologic toxicities occurred in 94%, including Grade 3 (16%) of patients. 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. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications [see Boxed Warning and Adverse Reactions (6.1 , 6.2) ] . Dose modifications for Vectibix concerning dermatologic toxicity are provided [see Dosage and Administration (2.3) ] . 5.2 Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with RAS- Mutant mCRC Receiving Vectibix Monotherapy or in Combination with Oxaliplatin-based Chemotherapy Vectibix monotherapy or in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as " RAS " [see Indications and Usage (1) , Dosage and Administration (2.1) , Clinical Pharmacology (12.1) and Clinical Studies (14.3) ] . Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents [see Indications and Usage (1) and Clinical Pharmacology (12.1) ] . Additionally, in Study 20050203, 272 patients with RAS- mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis , overall survival (OS) was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS- mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone [see Indications and Usage (1) ] . 5.3 Electrolyte Depletion/Monitoring Vectibix can cause progressively decreasing serum magnesium levels leading to severe (Grade 3 or 4) hypomagnesemia. Among 229 patients who received Vectibix as monotherapy, decreased magnesium occurred in 38% including Grade 4 (1.3%) and Grade 3 (2.6%). Among 585 patients who received Vectibix in combination with FOLFOX, decreased magnesium occurred in 51% including Grade 4 (5%) and Grade 3 (6%). In 126 patients receiving Vectibix in combination with sotorasib across clinical studies, decreased magnesium occurred in 69%, including Grade 4 (2.4%) and Grade 3 (14%). Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. 5.4 Infusion Reactions In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC Grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix administration [see Adverse Reactions (6.1 , 6.2) ] . Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions [see Dosage and Administration (2.3) ] . 5.5 Acute Renal Failure Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix. Among 229 patients who received Vectibix as monotherapy, acute renal failure occurred in 2% including Grade 3 or 4 (2%). Among 585 patients who received Vectibix in combination with FOLFOX, acute renal failure occurred in 2% including Grade 3 or 4 (2%). In 126 patients receiving Vectibix in combination with sotorasib across clinical studies, acute renal failure occurred in 3.2% including Grade 3 (0.8%). Monitor patients for diarrhea and dehydration, provide supportive care (including anti-emetic or anti-diarrheal therapy) as needed, and withhold Vectibix if necessary. 5.6 Pulmonary Fibrosis/Interstitial Lung Disease (ILD) Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. Grade 1 ILD/pneumonitis occurred in 0.8% (1/126) of patients enrolled in clinical studies of Vectibix in combination with sotorasib. In the event of acute onset or worsening of pulmonary symptoms, interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary complications must be carefully considered. 5.7 Photosensitivity Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix. 5.8 Ocular Toxicities Serious cases of keratitis, ulcerative keratitis, and corneal perforation have occurred with Vectibix use. Among 585 patients who received Vectibix in combination with FOLFOX, keratitis occurred in 0.3%. In 126 patients receiving Vectibix in combination with…