Panitumumab
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Alberto Plate [3]
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Black Box Warning
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Warning: Dermatological Toxicity
See full prescribing information for complete Boxed Warning.
Condition Name: 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.
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Overview
Panitumumab is an Immunological Agent and Monoclonal Antibody that is FDA approved for the treatment of metastatic colorectal cancer with wild-type KRAS (exon 2 in codons 12 or 13) as first-line therapy in combination with FOLFOX, monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding Panitumumab FDA-Labeled Indications and Dosage (Adult) in the drug label.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Panitumumab in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Panitumumab in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Panitumumab FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Panitumumab in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Panitumumab in pediatric patients.
Contraindications
None.
Warnings
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Warning: Dermatological Toxicity
See full prescribing information for complete Boxed Warning.
Condition Name: 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.
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Dermatologic and Soft Tissue Toxicity
In Study 1, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix. The clinical manifestations included, but were not limited to, acneiform dermatitis, 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. 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 (eg, 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. Dose modifications for Vectibix concerning dermatologic toxicity are provided.
Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with RAS- and KRAS-Mutant mCRC
A predefined retrospective subset analysis of Study 3 further identified a shortening of progression-free survival (PFS) and overall survival (OS) in patients with RAS-mutant tumors who received Vectibix and FOLFOX versus FOLFOX alone. Determination of RAS-mutant tumor status should be performed by an experienced laboratory.
Determination of KRAS mutational status in colorectal tumors using an FDA-approved test indicated for this use is necessary for selection of patients for treatment with Vectibix. Vectibix is indicated only for the treatment of patients with KRAS wild-type mCRC. Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in codons 12 and 13 (exon 2) as determined by an FDA-approved test for this use. In Study 3, 221 patients with KRAS-mutant mCRC tumors receiving Vectibix in combination with FOLFOX experienced shorter OS compared to 219 patients receiving FOLFOX alone (HR = 1.16, 95% CI: 0.94-1.41). Perform the assessment for KRAS mutational status in colorectal cancer in laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance can lead to unreliable test results. Refer to an FDA-approved test’s package insert for instructions on the identification of patients eligible for the treatment of Vectibix.
Electrolyte Depletion/Monitoring
Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 2) of patients across clinical trials. 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.
Infusion Reactions
In Study 1, 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. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
Acute Renal Failure in Combination with Chemotherapy
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
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. 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.
Photosensitivity
Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix.
Ocular Toxicities Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix therapy for acute or worsening keratitis.
5.9 Increased Mortality and Toxicity with Vectibix in Combination with Bevacizumab and Chemotherapy
In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix to the combination of bevacizumab and chemotherapy resulted in decreased OS 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/acneiform dermatitis (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 3%) and included fatal events in three (< 1%) Vectibix-treated patients.
As a result of the toxicities experienced, patients randomized to Vectibix, 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.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Panitumumab Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Panitumumab Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Panitumumab Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Panitumumab in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Panitumumab in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Panitumumab during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Panitumumab in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Panitumumab in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Panitumumab in geriatric settings.
Gender
There is no FDA guidance on the use of Panitumumab with respect to specific gender populations.
Race
There is no FDA guidance on the use of Panitumumab with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Panitumumab in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Panitumumab in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Panitumumab in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Panitumumab in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Panitumumab Administration in the drug label.
Monitoring
There is limited information regarding Panitumumab Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Panitumumab and IV administrations.
Overdosage
There is limited information regarding Panitumumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Panitumumab Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Panitumumab Mechanism of Action in the drug label.
Structure
There is limited information regarding Panitumumab Structure in the drug label.
Pharmacodynamics
There is limited information regarding Panitumumab Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Panitumumab Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Panitumumab Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Panitumumab Clinical Studies in the drug label.
How Supplied
There is limited information regarding Panitumumab How Supplied in the drug label.
Storage
There is limited information regarding Panitumumab Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Panitumumab Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Panitumumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Panitumumab Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Panitumumab Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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WikiDoc Resources for Panitumumab |
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Most recent articles on Panitumumab Most cited articles on Panitumumab |
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Media |
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Powerpoint slides on Panitumumab |
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Evidence Based Medicine |
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Clinical Trials |
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Ongoing Trials on Panitumumab at Clinical Trials.gov Clinical Trials on Panitumumab at Google
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Guidelines / Policies / Govt |
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US National Guidelines Clearinghouse on Panitumumab
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Books |
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News |
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Commentary |
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Definitions |
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Patient Resources / Community |
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Patient resources on Panitumumab Discussion groups on Panitumumab Patient Handouts on Panitumumab Directions to Hospitals Treating Panitumumab Risk calculators and risk factors for Panitumumab
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Healthcare Provider Resources |
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Causes & Risk Factors for Panitumumab |
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Continuing Medical Education (CME) |
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Experimental / Informatics |
Overview
Panitumumab (ABX-EGF) is a fully human monoclonal antibody specific to the EGF receptor (see illustration)[4]. It was FDA approved for the first time in September 2006, for the "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment [1]. Panitumumab is manufactured by Amgen and marketed as Vectibix in the USA.
The compound works by binding to the extracellular domain of the EGFR (epidermal growth factor receptor) preventing its activation. This in turn, results in halting of the cascade of intracellular signals dependent on this receptor. [2]
Panitumumab is produced by immunization of transgenic mice (xenomouse), that are able to produce human immunoglobulin light and heavy chains. After immunization of these animals a specific clone of B cells that produced an antibody against EGFR was selected and immortalized in Chinese hamster ovary (CHO) cells. These cells are then used for the full scale manufacture of the antibody.
Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate ADCC (antibody-dependent cellular cytotoxicity) better than their IgG2 counterparts, hence although they have not been documented, differences in the responses in treatments with these two antibodies might be expected. [5]
References
Further readings
Philippe Rougier, Emmanuel Mitry, Sophie Dominguez. Les Cancers Digestifs ; Springer , September 1, 2006, page=291 ; language=French