The primary undesirable effects of cetuximab are skin reactions, which occur in >80% of patients, hypomagnesaemia which occurs in >10% of patients and infusion-related reactions, which occur with mild to moderate symptoms in >10% of patients and with severe symptoms in >1% of patients.
The following definitions apply to the frequency terminology used hereafter: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and frequency not known (cannot be estimated from the available data).
An asterisk (*) indicates that additional information on the respective adverse reactions is provided as follows: Nervous System Disorders: Common: Headache. Frequency Not Known: Aseptic meningitis.
Eye Disorders: Common: Conjunctivitis. Uncommon: Blepharitis, keratitis.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Pulmonary embolism, interstitial lung disease.
Gastrointestinal Disorders: Common: Diarrhoea, nausea, vomiting.
Skin and Subcutaneous Tissue Disorders: Very Common: Skin reactions*. Frequency Not Known: Superinfection of skin lesions*.
Metabolism and Nutritional Disorders: Very Common: Hypomagnesaemia (see Precautions). Common: Dehydration, in particular secondary to diarrhoea or mucositis; hypocalcaemia (see Precautions); anorexia which may lead to decrease in weight.
Vascular Disorders: Uncommon: Deep vein thrombosis.
General Disorders and Administration Site Conditions: Very Common: Mild or moderate infusion-related reactions*; mild to moderate mucositis which may lead to epistaxis. Common: Severe infusion-related reactions*, fatigue.
Hepatobiliary Disorders: Very Common: Increase in liver enzyme levels (ASAT, ALAT, AP).
Additional Information*: Overall, no clinically relevant difference between genders was observed.
Infusion-Related Reactions: Mild or moderate infusion-related reactions are very common comprising symptoms eg, fever, chills, dizziness, or dyspnoea that occur in a close temporal relationship mainly to the 1st cetuximab infusion.
Severe infusion-related reactions may commonly occur, in rare cases with fatal outcome. They usually develop during or within 1 hr of the initial cetuximab infusion, but may occur after several hrs or with subsequent infusions. Although the underlying mechanism has not been identified, some of these reactions may be anaphylactoid/anaphylactic in nature and may include symptoms eg, bronchospasm, urticaria, increase/decrease of blood pressure, loss of consciousness or shock. In rare cases, angina pectoris, myocardial infarction or cardiac arrest have been observed.
For clinical management of infusion-related reactions, see Precautions.
Skin Reactions: Skin reactions may develop in >80% of patients and mainly present as acne-like rash and/or less frequently, as pruritus, dry skin, desquamation, hypertrichosis, or nail disorders (eg, paronychia).
Approximately 15% of the skin reactions are severe, including single cases of skin necrosis. The majority of skin reactions develop within the first 3 weeks of therapy. They generally resolve, without sequelae, over time following cessation of treatment if the recommended adjustments in dose regimen are followed (see Precautions).
Skin lesions induced by cetuximab may predispose patients to superinfections (eg, with Staphylococcus aureus), which may lead to subsequent complications eg, cellulitis, erysipelas, or potentially with fatal outcome, staphylococcal scalded skin syndrome or sepsis.
Combination Treatment: When cetuximab is used in combination with chemotherapeutic agents, also refer to their respective product information.
In combination with platinum-based chemotherapy, the frequency of severe leukopenia or severe neutropenia may be increased, and thus may lead to a higher rate of infectious complications eg, febrile neutropenia, pneumonia and sepsis compared to platinum-based chemotherapy alone (see Precautions).
In combination with infusional 5-fluorouracil, the frequency of cardiac ischaemia including myocardial infarction and congestive heart failure as well as the frequency of hand-foot syndrome (palmar-plantar erythrodysaesthesia) were increased compared to that with infusional 5-fluorouracil.
In combination with local radiation therapy of the head and neck area, additional undesirable effects were those typical of radiation therapy (eg, mucositis, radiation dermatitis, dysphagia or leukopenia, mainly presenting as lymphocytopenia). In a randomised controlled clinical study with 424 patients, reporting rates of severe acute radiation dermatitis and mucositis as well as of late radiation therapy-related events were slightly higher in patients receiving radiation therapy in combination with cetuximab than in those receiving radiation therapy alone.