Erbitux

Erbitux,

a trademark for cetuximab.

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cetuximab Warning - High-alert drug!

Erbitux

Pharmacologic class: Epidermal growth factor receptor (EGFR) inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category C

FDA Boxed Warning

• Drug may cause severe infusion reactions (rarely fatal). Approximately 90% of such reactions occur with first infusion. If severe reaction occurs, stop infusion immediately and discontinue therapy permanently.
• Cardiopulmonary arrest, sudden death, or both occurred in 2% of patients with squamous-cell carcinoma of head and neck who received drug plus radiation therapy (compared to none of 212 patients treated with radiation therapy alone). Fatal events occurred within 1 to 43 days after last drug administration. When combined with radiation therapy, drug should be used cautiously in head and neck cancer patients with known coronary artery disease, congestive heart failure, and arrhythmias. Monitor serum electrolyte levels closely during and after therapy.

Action

Binds to EGFR, competitively inhibiting binding of epidermal growth factor and other ligands and blocking phosphorylation and activation of receptor-associated kinases. These actions lead to cell growth inhibition, apoptosis induction, and decreased matrix metalloproteinases and vascular endothelial growth factor.

Availability

Solution for injection: 50-ml single-use vial containing 100 mg

⊘Indications and dosages

➣ EGFR-expressing metastatic colorectal carcinoma, used alone in patients intolerant to irinotecan-based chemotherapy or in combination with irinotecan in patients refractory to irinotecan-based therapy

Adults: 400 mg/m² initial loading dose given as 120-minute I.V. infusion followed by maintenance dose of 250 mg/m² infused I.V. over 60 minutes

➣ Locally or regionally advanced squamous-cell carcinoma of head and neck, in combination with radiation therapy

Adults: 400 mg/m² as initial loading dose (first infusion) given as 120-minute I.V. infusion 1 week before initiation of radiation therapy. For recommended weekly maintenance dose (all other infusions), 250 mg/m² infused I.V. over 60 minutes weekly for duration of radiation therapy (6 to 7 weeks) given 1 hour before radiation therapy.

➣ Recurrent or metastatic squamous-cell carcinoma of head and neck (used alone) in patients for whom platinum-based therapy has failed

Adults: Initially, 400-mg/m² I.V. infusion followed by 250 mg/m² I.V. weekly until disease progresses or unacceptable toxicity occurs

Off-label uses

• Cancers that overexpress EGFR

Dosage adjustment

• Mild to moderate infusion (Grade 1 or 2) reaction
• Severe acneiform rash
• Acute onset or worsening of pulmonary symptoms

Contraindications

None

Precautions

Use cautiously in:
• hypersensitivity to murine proteins or drug components
• dermatologic or pulmonary toxicities
• patients receiving concurrent radiation therapy and cisplatin
• patients receiving concurrent radiation therapy who have history of coronary artery disease, arrhythmias, and congestive heart failure
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• As ordered, premedicate with histamine₁-antagonist (such as 50 mg diphenhydramine I.V.).
• Use low-protein-binding, 0.22 micrometer in-line filter placed as close to patient as possible.
☞ Don't give by I.V. push or bolus.
☞ Don't shake or dilute vial.
• Administer by I.V. infusion pump or syringe pump.
• Piggyback drug to patient's infusion line.
• Give initial dose over 2 hours at a rate of 5 ml/minute; give subsequent weekly doses over 1 hour. Maximum infusion rate shouldn't exceed 5 ml/minute.
• At end of infusion, flush I.V. lines with normal saline solution.
• Observe patient closely for 1 hour after infusion (or longer in patients who experience infusion reactions). Severe and life-threatening infusion reactions have occurred, including rapid-onset airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and hypotension.
• Permanently reduce infusion rate by 50% if patient experiences mild or moderate infusion reaction. Immediately and permanently discontinue drug in patient who experiences severe (Grade 3 or 4) infusion reaction.
• Expect patients with colorectal cancer to undergo immunohistochemical testing for EGFR expression using DakoCytomation EGFR pharmDx test kit.
• Make sure appropriate medical resources for treatment of severe infusion reactions are available during infusion.
• Interrupt therapy if patient develops acute onset or worsening of pulmonary symptoms. Discontinue therapy if pneumonitis or lung infiltrates are confirmed.
• For first occurrence of severe acneiform rash, delay infusion 1 to 2 weeks; if condition improves, continue therapy at 250 mg/m²; if no improvement occurs, withdraw drug. For second occurrence, delay infusion 1 to 2 weeks; if condition improves, reduce dosage to 200 mg/m²; if no improvement occurs, withdraw drug. For third occurrence, delay infusion for 1 to 2 weeks; if condition improves, reduce dosage to 150 mg/m²; if no improvement occurs, withdraw drug. On fourth occurrence, withdraw drug.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

Adverse reactions

CNS: headache, insomnia, depression, malaise, asthenia

CV: cardiopulmonary arrest

EENT: conjunctivitis

GI: abdominal pain, diarrhea, nausea, vomiting, constipation, stomatitis, dyspepsia, anorexia

GU: renal failure

Hematologic: leukopenia, anemia

Metabolic: dehydration, electrolyte abnormalities

Musculoskeletal: back pain

Respiratory: dyspnea, increased cough, interstitial lung disease, pulmonary embolus

Skin: acneiform rash, alopecia, skin disorder, nail disorder, pruritus

Other: weight loss, fever, pain, infection, peripheral edema, severe infusion reaction

Interactions

Drug-diagnostic tests. Calcium, magnesium: decreased

Drug-behaviors. Sun exposure: exacerbated skin reactions

Patient monitoring

• Watch for signs and symptoms of infusion reaction.
• Monitor patient for hypomagnesemia and hypocalcemia during therapy and for 8 weeks afterward.
• Closely monitor serum electrolytes (including serum magnesium, potassium, and calcium) during therapy and after combination drug and radiation therapy in patients with history of coronary artery disease, arrhythmias, and heart failure.
• Monitor patient with dermatologic toxicities for inflammatory or infectious sequelae.
• Watch for pulmonary toxicities in patient with history of interstitial pneumonitis or pulmonary fibrosis. Be prepared to interrupt or discontinue therapy and intervene appropriately.
• Monitor for potentially serious cardiotoxicity if patient is receiving drug in combination with radiation therapy and cisplatin.
• Stay alert for severe diarrhea and electrolyte depletion.

Patient teaching

☞ Urge patient to immediately report rash, which may indicate skin toxicity.
☞ Instruct patient to immediately report new or worsening respiratory or cardiovascular symptoms.
• Advise patient to use sunscreen and wear a hat when outdoors and to limit sun exposure, because sunlight can exacerbate skin reactions.
• Caution female with childbearing potential that drug may cause pregnancy loss or pose hazard to fetus.
• Advise female to discontinue breastfeeding during therapy and for 60 days after last dose.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests and behaviors mentioned above.