cinoma of the head and neck treated with Vectibix in a clinical trial. The fatal event occurred after re-exposure following a prior episode of angioedema; both episodes occurred greater than 24 hours after administration (see sections 4.3 and 4.4). Hypersensitivity reactions occurring more than 24 hours after infusion have also been reported in the post-marketing setting.
For clinical management of infusion-related reactions, see section 4.4.
Skin and subcutaneous tissue disorders
Skin rash most commonly occurred on the face, upper chest, and back, but could extend to the extremities. Subsequent to the development of severe skin and subcutaneous reactions, infectious complications including sepsis, in rare cases leading to death, cellulitis and local abscesses requiring incisions and drainage were reported. The median time to first symptom of dermatologic reaction was 10 days, and the median time to resolution after the last dose of Vectibix was 28 days.
Paronychial inflammation was associated with swelling of the lateral nail folds of the toes and fingers.
Dermatological reactions (including nail effects), observed in patients treated with Vectibix or other EGFR inhibitors, are known to be associated with the pharmacologic effects of therapy.
Across all clinical trials, skin reactions occurred in 93% of patients receiving Vectibix as monotherapy or in combination with chemotherapy (n = 2588). These events consisted predominantly of rash and dermatitis acneiform and were mostly mild to moderate in severity. Severe (NCI-CTC grade 3) skin reactions were reported in 34% and life-threatening (NCI-CTC grade 4) skin reactions in < 1% of patients who received Vectibix in combination with chemotherapy (n = 1536).
For clinical management of dermatological reactions, including dose modification recommendations, see section 4.4.
In the post-marketing setting, cases of skin necrosis have been reported.
Paediatric population
There is no experience in children and Vectibix should not be used in those patients less than 18 years of age.
Other special populations
No overall differences in safety or efficacy were observed in elderly patients ( 65 years of age) treated with Vectibix monotherapy. However, an increased number of serious adverse events were reported in elderly patients treated with Vectibix in combination with FOLFIRI (45% vs 37%) or FOLFOX (52% vs 37%) chemotherapy compared to chemotherapy alone (see Section 4.4). The most increased serious adverse events were diarrhoea in patients treated with Vectibix in combination with either FOLFOX or FOLFIRI, and dehydration and pulmonary embolism when patients were treated with Vectibix in combination with FOLFIRI.
Ocular toxicities
Non-serious cases of keratitis have been observed in 0.2 to 0.7% of clinical trial patients. In the post-marketing setting, serious cases of keratitis and ulcerative keratitis have been rarely reported (see section 4.4).
The safety of Vectibix has not been studied in patients with renal or hepatic impairment.
4.9 Overdose
Doses up to 9 mg/kg have been tested in clinical trials. There have been reports of overdose at doses up to approximately twice the recommended therapeutic dose (12 mg/kg). Adverse events observed included skin toxicity, diarrhoea, dehydration and fatigue and were consistent with the safety profile at the recommended dose.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeut |
