Very commonly reported adverse reactions occurring in ≥ 20% of patients were gastrointestinal disorders [diarrhoea (46%), nausea (39%), vomiting (26%), constipation (23%) and abdominal pain (23%)]; general disorders [fatigue (35%), pyrexia (21%)]; metabolism and nutrition disorders [decreased appetite (30%)]; infections and infestations [paronychia (20%)]; and skin and subcutaneous disorders [rash (47%), dermatitis acneiform (39%), pruritus (36%), erythema (33%) and dry skin (21%)].
Tabulated list of adverse reactions: The data in Table 7 as follows describe adverse reactions reported from clinical studies in patients with mCRC who received panitumumab as a single agent or in combination with chemotherapy (n = 2,224) and spontaneous reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 7.)
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The safety profile of Vectibix in combination with chemotherapy consisted of the reported adverse reactions of Vectibix (as a monotherapy) and the toxicities of the background chemotherapy regimen. No new toxicities or worsening of previously recognised toxicities beyond the expected additive effects were observed. Skin reactions were the most frequently occurring adverse reactions in patients receiving panitumumab in combination with chemotherapy. Other toxicities that were observed with a greater frequency relative to monotherapy included hypomagnesaemia, diarrhoea, and stomatitis. These toxicities infrequently led to discontinuation of Vectibix or of chemotherapy.
Description of selected adverse reactions: Gastrointestinal disorders: Diarrhoea when reported was mainly mild or moderate in severity. Severe diarrhoea (NCI-CTC grade 3 and 4) was reported in 2% of patients treated with Vectibix as a monotherapy and in 16% of patients treated with Vectibix in combination with chemotherapy.
There have been reports of acute renal failure in patients who develop diarrhoea and dehydration (see Precautions).
Infusion-related reactions: Across monotherapy and combination mCRC clinical studies (n = 2,224), infusion-related reactions (occurring within 24 hours of any infusion), which may include symptoms/signs such as chills, fever or dyspnoea, were reported in approximately 5% of Vectibix-treated patients, of which 1% were severe (NCI-CTC grade 3 and grade 4).
A case of fatal angioedema occurred in a patient with recurrent and metastatic squamous cell carcinoma 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 Contraindications and Precautions). 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 Precautions
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 31 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 approximately 94% of patients receiving Vectibix as monotherapy or in combination with chemotherapy (n = 2,224). 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 23% and life-threatening (NCI-CTC grade 4) skin reactions in < 1% of patients. Life threatening and fatal infectious complications including necrotising fasciitis and sepsis have been observed in patients treated with Vectibix (see Precautions).
For clinical management of dermatological reactions, including dose modification recommendations, see Precautions
In the post-marketing setting, rare cases of skin necrosis, Stevens-Johnson syndrome and toxic epidermal necrolysis (see Precautions) have been reported.
Ocular toxicities: Serious cases of keratitis and ulcerative keratitis, which may lead to corneal perforation, have been reported (see Precautions).
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% versus 32%) or FOLFOX (52% versus 37%) chemotherapy compared to chemotherapy alone (see Precautions). The most increased serious adverse events included 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.The safety of Vectibix has not been studied in patients with renal or hepatic impairment.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
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