Dosage & Administration
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Vectibix Prescribing Information
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC Grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
Metastatic Colorectal Cancer (mCRC)
- RAS Wild-Type mCRC
Vectibix is indicated for the treatment of adult patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal cancer (mCRC) [see Dosage and Administration (2.1)]:- As first-line therapy in combination with FOLFOX [see Clinical Studies (14.2)].
- As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy [see Clinical Studies (14.1)].
- KRAS G12C-mutated mCRC
Vectibix, in combination with sotorasib, is indicated for the treatment of adult patients with KRAS G12C-mutated mCRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy [see Dosage and Administration (2.1) and Clinical Studies (14.4)].
Limitations of Use: Vectibix is not indicated for the treatment of patients with RAS-mutant mCRC unless used in combination with sotorasib in KRAS G12C-mutated mCRC. Vectibix is not indicated for the treatment of patients with mCRC for whom RAS mutation status is unknown [see Dosage and Administration (2.1), Warnings and Precautions (5.2), Clinical Pharmacology (12.1) and Clinical Studies (14.3)].
Patient Selection
RAS Wild-Type mCRC
Prior to initiation of treatment with Vectibix as monotherapy, assess RAS mutational status in colorectal tumors and confirm the absence of a RAS mutation in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of both KRAS and NRAS.
KRAS G12C-mutated mCRC
Prior to initiation of treatment with Vectibix in combination with sotorasib, confirm the presence of the KRAS G12C mutation using an FDA-approved test.
Information on FDA-approved tests for the detection of RAS mutations in patients with mCRC is available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage
RAS Wild-Type mCRC
The recommended dosage of Vectibix is 6 mg/kg, administered as an intravenous infusion every 14 days until disease progression or unacceptable toxicity [see Dosage and Administration (2.4)].
Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions [see Warnings and Precautions (5.4)].
KRAS G12C-mutated mCRC
Administer the first sotorasib dose prior to the first Vectibix infusion.
The recommended dosage for Vectibix in combination with sotorasib is 6 mg/kg, administered as an intravenous infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued [see Dosage and Administration (2.3, 2.4)]. Refer to the sotorasib full prescribing information for recommended sotorasib dosing information.
Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions [see Warnings and Precautions (5.4)].
Dose Modifications
Dose Modifications for Vectibix in Combination with Sotorasib
When Vectibix is administered in combination with sotorasib, if treatment with sotorasib is temporarily withheld or permanently discontinued, temporarily withhold or permanently discontinue Vectibix, respectively [see Clinical Studies (14.4)].
Refer to the sotorasib full prescribing information for dose modifications for adverse reactions associated with the use of sotorasib.
Dose Modifications for Specific Adverse Reactions Associated with the Use of Vectibix
Infusion Reactions [see Warnings and Precautions (5.4) and Adverse Reactions (6.1, 6.2)]
- Reduce infusion rate by 50% in patients experiencing a mild or moderate (Grade 1 or 2) infusion reaction for the duration of that infusion.
- Terminate the infusion in patients experiencing severe infusion reactions. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix.
Dermatologic Toxicity [see Boxed Warning, Warnings and Precautions (5.1) and Adverse Reactions (6.1, 6.2)]
- Upon first occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < Grade 3, reinitiate Vectibix at the original dose.
- Upon the second occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < Grade 3, reinitiate Vectibix at 80% of the original dose.
- Upon the third occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < Grade 3, reinitiate Vectibix at 60% of the original dose.
- Upon the fourth occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, permanently discontinue Vectibix.
Permanently discontinue Vectibix following the occurrence of a Grade 4 dermatologic reaction or for a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction that does not recover after withholding 1 or 2 doses.
Preparation and Administration
For intravenous infusion only. Do not administer Vectibix as an intravenous push or bolus.
Preparation
Visually inspect parenteral drug products for particulate matter and discoloration prior to administration. Vectibix solution is colorless and may contain a small amount of visible translucent-to-white, amorphous, proteinaceous particles. Do not use if the solution is discolored or cloudy, or if foreign matter is present.
Prepare the solution for infusion, using aseptic technique, as follows:
- Do not shake the vial.
- Use a 21-gauge or larger gauge (smaller bore) hypodermic needle to withdraw the necessary amount of Vectibix for a dose of 6 mg/kg. Do not use needle-free devices (e.g., vial adapters) to withdraw vial contents.
- Dilute to a total volume of 100 mL with 0.9% sodium chloride injection, USP. Doses higher than 1000 mg should be diluted to 150 mL with 0.9% sodium chloride injection, USP. Do not exceed a final concentration of 10 mg/mL.
- Mix diluted solution by gentle inversion.
- Discard any unused portion of the vial.
Administration
- Administer using a low-protein-binding 0.2 µm or 0.22 µm in-line filter.
- Vectibix must be administered via infusion pump.
- Flush line before and after Vectibix administration with 0.9% sodium chloride injection, USP, to avoid mixing with other drug products or intravenous solutions. Do not mix Vectibix with, or administer as an infusion with, other medicinal products. Do not add other medications to solutions containing panitumumab.
- Infuse doses of 1000 mg or lower over 60 minutes through a peripheral intravenous line or indwelling intravenous catheter. If the first infusion is tolerated, administer subsequent infusions over 30 to 60 minutes. Administer doses higher than 1000 mg over 90 minutes.
- 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°C (36° to 46°F). DO NOT FREEZE.
Injection: 100 mg/5 mL (20 mg/mL) colorless solution in single-dose vial.
Injection: 400 mg/20 mL (20 mg/mL) colorless solution in single-dose vial.
Pregnancy
Risk Summary
Based on data from animal studies and its mechanism of action, Vectibix can cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1)]. Limited available data on the use of Vectibix in pregnant women are not sufficient to inform a risk of adverse pregnancy-related outcomes. Vectibix is a human IgG monoclonal antibody and may be transferred across the placenta during pregnancy. 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 Data]. Advise pregnant women of the potential risk to the fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Based on animal models, EGFR is involved in prenatal development and may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo. Pregnant cynomolgus monkeys were treated weekly with panitumumab during the period of organogenesis (gestation day [GD] 20-50). While no panitumumab was detected in serum of neonates from panitumumab-treated dams, anti-panitumumab antibody titers were present in 14 of 27 offspring delivered at GD 100. There were no fetal malformations or other evidence of teratogenesis noted in the offspring; however, significant increases in embryolethality and abortions occurred at doses of approximately 1.25 to 5 times the recommended human dose (based on body weight).
Lactation
Risk Summary
There are no data on the presence of panitumumab in human milk or the effects of panitumumab on the breastfed infant or on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential for serious adverse reactions in breastfed infants from Vectibix, advise women not to breastfeed during treatment with Vectibix and for 2 months after the last dose.
Females and Males of Reproductive Potential
Contraception
Females
Vectibix can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Vectibix and for 2 months after the last dose of Vectibix.
Infertility
Females
Based on results from animal fertility studies conducted in female cynomolgus monkeys, Vectibix may reduce fertility in females of reproductive potential. The effects in animal studies were reversible [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness of Vectibix have not been established in pediatric patients.
The pharmacokinetics of panitumumab at doses ranging from 2.5 mg/kg intravenous weekly, 6 mg/kg intravenous every 2 weeks, or 9 mg/kg intravenous every 3 weeks were evaluated in 28 pediatric patients. Panitumumab exposures were comparable in adult and adolescent patients of 12 to 17 years of age. Limited data suggested that pediatric patients of 2 to < 12 years of age had lower panitumumab exposure and higher clearance than that in adolescent patients following 6 mg/kg intravenous administration of Vectibix. There was no evidence of an anti-tumor treatment effect in these patients.
Geriatric Use
Of the 737 patients who received Vectibix monotherapy for recurrent or refractory mCRC [see Clinical Studies (14.1)], 36% were 65 and over while 8% were 75 and over. No overall differences in safety or efficacy were observed in elderly patients (≥ 65 years of age) treated with Vectibix monotherapy.
Of the 322 patients who received Vectibix plus FOLFOX, for wild-type KRAS-mutated mCRC [see Clinical Studies (14.2)], 128 (40%) were 65 and over while 8% were 75 and over. Patients older than 65 years of age experienced an increased incidence of serious adverse events (52% vs 36%) and an increased incidence of serious diarrhea (15% vs 5%) as compared to younger patients.
In a pooled analysis of 132 patients who received Vectibix in combination with sotorasib 960 mg for KRAS G12C-mutated mCRC, 30% were 65 and over while 9% were 75 and over. No overall differences in safety or efficacy were observed in elderly patients (≥ 65 years of age) compared to younger patients treated with Vectibix in combination with sotorasib.
None.