Leitlinien & Arzneimittelsicherheit

HOS-094608 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Based on an analysis of all mCRC clinical trial patients receiving Vectibix monotherapy and in combination with chemotherapy (n = 2 224), the most commonly reported adverse reactions are skin reactions occurring in approximately 94% of patients. These reactions are related to the pharmacologic effects of Vectibix, and the majority are mild to moderate in nature with 23% severe (grade 3) and < 1% life-threatening (grade 4). For clinical management of skin reactions, including dose modification recommendations, see section 4.4. 7 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 the table below 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. Adverse reactions MedDRA Very common Common Uncommon system organ (≥ 1/10) (≥ 1/100 to < 1/10) (≥ 1/1 000 to class < 1/100) Infections and Conjunctivitis Rash pustular Eye infection infestations Paronychia1 Cellulitis1 Eyelid infection Urinary tract infection Folliculitis Localised infection Blood and Anaemia Leucopenia lymphatic system disorders Immune system Hypersensitivity1 Anaphylactic disorders

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HOS-094604 · has-contraindication-information · PDF-Seite 4

Patients with a history of severe or life-threatening hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4). Patients with interstitial pneumonitis or pulmonary fibrosis (see section 4.4). The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC status is unknown (see section 4.4).

HOS-094603 · has-indication-information · PDF-Seite 2

Vectibix is indicated for the treatment of adult patients with wild-type RAS metastatic colorectal cancer (mCRC): • in first-line in combination with FOLFOX or FOLFIRI. • in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan). • as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

HOS-094606 · has-interaction-information · PDF-Seite 6

Data from an interaction study involving Vectibix and irinotecan in patients with mCRC indicated that the pharmacokinetics of irinotecan and its active metabolite, SN-38, are not altered when the medicinal products are co-administered. Results from a cross-study comparison indicated that irinotecan-containing regimens (IFL or FOLFIRI) have no effect on the pharmacokinetics of panitumumab. 6 Vectibix should not be administered in combination with IFL chemotherapy or with bevacizumab-containing chemotherapy. A high incidence of severe diarrhoea was observed when panitumumab was administered in combination with IFL (see section 4.4), and increased toxicity and deaths were seen when panitumumab was combined with bevacizumab and chemotherapy (see sections 4.4 and 5.1). The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC status is unknown. A shortened progression-free survival and overall survival time were observed in a clinical study in patients with mutant RAS tumours who received panitumumab and FOLFOX (see sections 4.4 and 5.1).

HOS-094607 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are no adequate data from the use of Vectibix in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. EGFR has been implicated in the control of prenatal development and may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo. Therefore, Vectibix has the potential to cause foetal harm when administered to pregnant women. Human IgG is known to cross the placental barrier, and panitumumab may therefore be transmitted from the mother to the developing foetus. In women of childbearing potential, appropriate contraceptive measures must be used during treatment with Vectibix, and for 2 months following the last dose. If Vectibix is used during pregnancy or if the patient becomes pregnant while receiving this medicinal product, she should be advised of the potential risk for loss of the pregnancy or potential hazard to the foetus. Breast-feeding It is unknown whether panitumumab is excreted in human breast milk. Because human IgG is secreted into human milk, panitumumab might also be secreted. The potential for absorption and harm to the infant after ingestion is unknown. It is recommended that women do not breast-feed during treatment with Vectibix and for 2 months after the last dose. Fertility Animal studies have shown reversible effects on the menstrual cycle and reduced female fertility in monkeys (see section 5.3). Panitumumab may impact the ability of a woman to become pregnant.

HOS-094605 · has-warning-information · PDF-Seite 4

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Dermatologic reactions and soft tissue toxicity Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, are experienced with nearly all patients (approximately 94%) treated with Vectibix. Severe (NCI-CTC grade 3, where grading is defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)) skin reactions were reported in 23% and life-threatening (grade 4) skin reactions in < 1% of patients who received Vectibix monotherapy and in combination with chemotherapy (n = 2 224) (see section 4.8). If a patient develops dermatologic reactions that are grade 3 (CTCAE v5.0) or higher, or that are considered intolerable, see the recommendation for dose modification in section 4.2. In clinical studies, subsequent to the development of severe dermatologic reactions (including stomatitis), infectious complications including sepsis and necrotising fasciitis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or soft tissue toxicity or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae (including cellulitis and necrotising fasciitis), and appropriate treatment promptly initiated. Life-threatening and fatal infectious complications including necrotising fasciitis and sepsis have been observed in patients treated with Vectibix. Rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in patients treated with Vectibix in the post-marketing setting. Withhold or discontinue Vectibix in the event of dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Treatment and management of dermatologic reactions should be based on severity and may include a moisturiser, sunscreen (SPF > 15 UVA and UVB), and topical steroid cream (not stronger than 1% hydrocortisone) applied to affected areas, and/or oral antibiotics (e.g. doxycycline). It is also recommended that patients experiencing rash/dermatological toxicities wear sunscreen and hats and limit sun exposure as sunlight can exacerbate any skin reactions that may occur. Patients may be ad

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