Cetuximab

CETUXIMAB (ERBITUX) — CLINICIAN SUMMARY

🔴 RED FLAG (IMPORTANT) INFORMATION

(Key safety and prescribing points)

• RAS mutation = NO benefit in colorectal cancer → confirm RAS wild-type before prescribing.

• Severe infusion reactions can be fatal, especially with the first dose → premedication and close monitoring required.

• Acneiform skin rash is very common (>80%) and can lead to serious skin infections, sepsis, necrotising fasciitis.

• Electrolyte disturbances (hypomagnesaemia ± hypocalcaemia/hypokalaemia) are common → monitor and replace.

• Pulmonary toxicity (rare) and severe mucocutaneous reactions (SJS/TEN) reported → stop permanently if suspected.

• Cardiac ischaemia risk increases when combined with fluoropyrimidines.

• Ocular toxicity (keratitis, corneal ulceration) → interrupt or discontinue if confirmed.

1. BASIC INFORMATION

• Generic name: Cetuximab

• Brand name: ERBITUX

• Drug class: EGFR monoclonal antibody (IgG1)

• Formulation: IV solution for infusion

• Strength: 5 mg/mL

  • 100 mg / 20 mL

  • 500 mg / 100 mL

2. INDICATIONS

Metastatic colorectal cancer (mCRC)

• EGFR-expressing, RAS wild-type tumours only

• Used:

  • In combination with chemotherapy (FOLFOX, FOLFIRI)

  • As monotherapy after chemotherapy failure

Squamous cell carcinoma of head and neck (SCCHN)

• Locally advanced disease with radiotherapy

• Recurrent or metastatic disease with platinum-based chemotherapy

• Platinum-refractory recurrent/metastatic disease (monotherapy)

3. DOSING & ADMINISTRATION

Standard dosing

• Loading dose:

  • 400 mg/m² IV over 120 minutes

• Maintenance dose:

  • 250 mg/m² IV weekly over 60 minutes

Administration notes

• Premedicate with antihistamine ± corticosteroid

• Use separate IV line

• Infuse via pump or gravity drip

• Do not mix with other IV drugs

• Observe patient during and after infusion

4. DOSE MODIFICATIONS

Infusion reactions

• Grade 1–2: Slow infusion, symptomatic management

• Grade 3–4: Permanently discontinue

Skin toxicity

• Grade 1–2: Continue + supportive care

• Grade 3: Interrupt until ≤ Grade 2, then restart

• Grade 4: Permanently discontinue

Electrolyte abnormalities

• Correct deficiencies

• Interrupt treatment if severe or symptomatic

5. CO-MEDICATIONS

Common combinations

• FOLFOX, FOLFIRI

• Platinum-based chemotherapy

• Radiotherapy (SCCHN)

Supportive care often required

• Oral/IV magnesium supplementation

• Emollients, topical antibiotics

• Oral doxycycline for rash prophylaxis

• Antihistamines ± steroids (infusion reactions)

6. CONTRAINDICATIONS

• Known hypersensitivity to cetuximab or murine proteins

• RAS-mutated colorectal cancer

• Pregnancy and breastfeeding (unless benefit outweighs risk)

7. MONITORING REQUIREMENTS

Baseline and ongoing

• RAS mutation status (CRC)

• Electrolytes: Mg²⁺, Ca²⁺, K⁺ (baseline and regularly)

• FBC: Especially with combination chemotherapy

• Liver enzymes

• Skin examination (weekly early in treatment)

Clinical monitoring

• Infusion reactions (especially first dose)

• Signs of infection or sepsis

• Visual symptoms (eye pain, redness, photophobia)

• Cardiac symptoms if on fluoropyrimidines

8. SIDE EFFECTS

Very common (>10%)

• Acneiform rash

• Hypomagnesaemia

• Infusion-related reactions

• Fatigue

• Mucositis

Common (1–10%)

• Diarrhoea

• Nausea, vomiting

• Nail changes (paronychia)

• Dry skin, pruritus

• Infections (secondary skin infections)

Serious / rare

• Severe infusion reactions (fatal)

• SJS / TEN

• Necrotising fasciitis, sepsis

• Keratitis, corneal ulceration

• Cardiac ischaemia (with fluoropyrimidines)

9. DRUG INTERACTIONS

• Platinum chemotherapy: ↑ severe neutropenia and infections

• Fluoropyrimidines: ↑ cardiac ischaemia, heart failure, hand-foot syndrome

• XELOX: ↑ severe diarrhoea

• No significant pharmacokinetic interactions identified

10. USE IN SPECIAL POPULATIONS

• Pregnancy: Avoid; fetal risk likely

• Breastfeeding: Contraindicated (stop for ≥2 months after last dose)

• Renal impairment: No dose adjustment

• Hepatic impairment: No dose adjustment

• Paediatrics: Not established

• Elderly: No specific adjustment

11. DURATION OF USE / WHEN TO STOP

Continue until:

• Disease progression, or

• Unacceptable toxicity

Permanently discontinue if:

• Grade 3–4 infusion reaction

• Confirmed SJS/TEN

• Severe or recurrent skin toxicity

• RAS mutation identified during CRC treatment

12. TOXICITY MANAGEMENT (SIMPLIFIED)

Skin rash

• Grade 1–2: Emollients ± doxycycline

• Grade 3: Hold, treat, restart when improved

• Grade 4: Discontinue permanently

Infusion reaction

• Mild: Slow infusion + antihistamine

• Severe: Stop immediately → never rechallenge

Electrolytes

• Replace magnesium aggressively

• Monitor for secondary hypocalcaemia

https://ec.europa.eu/health/documents/community-register/2023/20230424159203/anx_159203_en.pdf