panitumumab (Rx)

>10%

Erythema (65%)

Acneiform dermatitis (57%)

Pruritus (57%)

Hypomagnesemia (39%)

Fatigue (26%)

Abdominal pain (25%)

Paronychia (25%)

Skin exfoliation (25%)

Nausea (23%)

Rash (22%)

Constipation (21%)

Diarrhea (21%)

Vomiting (21%)

Skin fissures (20%)

Cough (14%)

Dermatologic toxicity, Grade 3 and 4 (14% )

Acne (13%)

Peripheral edema (12%)

1-10%

Abdominal pain, Grade 3 and 4 (7% )

Pulmonary embolism, Grades 3 to 5 (7% )

Hypomagnesemia, Grade 3 and 4 (4% )

Angioedema, All grades (3% to 4% )

Complication of infusion, All grades (3% to 4% )

Constipation, Grade 3 and 4 (3% )

Binding antibodies (0.4-3.8%)

Diarrhea, Grade 3 and 4 (2% )

Vomiting, Grade 3 and 4 (2% )

Nausea, Grade 3 and 4 (1% )

Anaphylaxis (1% )

Complication of infusion, Grade 3 and 4 (1% )

Sepsis (1%)

<1%

Pulmonary fibrosis

Frequency Not Defined

Conjunctivitis

Growth of eyelashes

Increased tears

Ocular hyperemia

Mucositis

Stomatitis

Postmarketing Reports

Skin and subcutaneous tissue disorders: Skin necrosis, angioedema

Immune system disorders: Anaphylactoid reaction

Eye disorders: Keratitis/ulcerative keratitis

Life threatening and fatal bullous mucocutaneous disease

Contraindications

None

Cautions

Increased tumor progression, increased mortality, or lack of benefit in patients with RAS-mutant mCRC; determine RAS-mutant tumor status in an experienced laboratory using an FDA-approved test before treatment

Monitor patients who develop dermatologic toxicities while receiving panitumumab for the development of inflammatory or infectious sequelae; limit sun exposure

Panitumumab is not indicated for use in combination with chemotherapy due to increase in mortality or toxicity

Permanently discontinue in patients developing pulmonary fibrosis/interstitial lung disease

Monitor electrolytes and institute appropriate treatment if needed

Terminate the infusion for severe infusion reactions

Ocular toxicities reported; monitor for keratitis or ulcerative keratitis; interrupt or discontinue for acute or worsening keratitis

Discontinue permanently if patient develops interstitial lung disease, pneumonitis, or lung infiltrates

Avoid pregnancy

Not indicated for 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 (RAS)

Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia reported; monitor patients for hypomagnesemia and hypocalcemia prior to initiating treatment, periodically during treatment, and for up to 8 weeks after completion of treatment; other electrolyte disturbances, including hypokalemia, have also been observed; replete magnesium and other electrolytes as appropriate

Dermatologic toxicity

• Clinical manifestations reported include, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures
• Severe dermatologic toxicities complicated by infection including sepsis, septic death, and abscesses requiring incisions and drainage
• 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) is unclear
• Withhold or discontinue panitumumab and monitor for inflammatory or infectious sequelae in patients with severe dermatologic toxicities

Pregnancy

Based on data from animal studies and mechanism of action; therapy can cause fetal harm when administered to pregnant women; limited available data on use of therapy in pregnant women are not sufficient to inform a risk of adverse pregnancy-related outcomes; panitumumab is a human IgG monoclonal antibody and may be transferred across the placenta during pregnancy; advise pregnant women of the potential risk to the fetus

Contraception

• Females: Therapy can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 2 months after last dose

Infertility

• Females: Based on results from animal fertility studies conducted in female cynomolgus monkeys, therapy may reduce fertility in females of reproductive potential; effects in animal studies were reversible.

Lactation

There are no data on presence of drug in human milk or effects of panitumumab on breastfed infant or on milk production; human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter neonatal and infant circulation in substantial amounts; because of potential for serious adverse reactions in breastfed infants from therapy, advise women not to breastfeed during treatment and for 2 months after final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Human monoclonal antibody to human EGF receptor

Pharmacokinetics

Peak Plasma Concentration: 213±59 mcg/mL

Trough Concentration: 39±14 mcg/mL

Half-Life, Elimination: 7.5 days

Clearance: 4.9±1.4 mL/kg/day

Pharmacogenomics

Colorectal cancer expressing with KRAS wild-type respond more favorably to regimens that include anti-EGFR antibodies (cetuximab, panitumumab); whereas, the presence of KRAS mutation (codon 12 or 13) showed an absence of biological and clinical activity for the anti-EGFR antibody treatment

Strongly recommended that patients with metastatic CRC who are being considered for treatment with anti-EGFR antibody therapy should be tested for the presence of a KRAS mutation prior to the administration of therapy (NCCN guidelines)

Genetic testing laboratories

• The following companies are currently offering KRAS mutation status testing
• Clarient, Inc. (http://www.clarientinc.com)
• Caris Diagnostics (http://www.carisdx.com)
• DxS (http://www.dxsdiagnostics.com)
• Genzyme Genetics (http://www.genzymegenetics.com)
• LabCorp (http://www.labcorp.com)
• Response Genetics (http://www.responsegenetics.com)

IV Preparation

Inspect vial; discard if discolored

Some particulate matter may be present, OK to use (will be removed by filter)

Withdraw dose amount & dilute to 100 mL with 0.9% NaCl (if dose >1 g, in 150 mL)

Mix by gentle inversion, do not shake

Final concentration not to exceed 10 mg/mL

Use diluted solution within 6 hr if stored at room temp, or within 24 hr if stored at 2-8°C

IV Administration

For IV infusion only; not for IV push or bolus

Use low-protein-binding 0.2-0.22 micron in-line filter

Flush IV line with 0.9% NaCl before and after administration

Use infusion pump

Doses &lge;1 g: Infuse over 60 min through peripheral line or indwelling catheter; ; if first infusion tolerated, administer subsequent infusion over 30-60 min

Doses >1 g: Infuse IV over 90 min

Storage

Unopened vials

• Store vials in the original carton under refrigeration at 2-8°C (36-46°F) until time of use
• Protect from direct sunlight
• Do not freeze
• Discard any unused solution remaining in the vial

Diluted solution

• Room temperature: Administer within 6 hr of preparation
• Refrigerated (2-8°C [36-46°]): Administer within 24 hr of preparation
• Do not freeze