Bavencio

HOS-098141 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile Avelumab is associated with immune-mediated adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of avelumab (see “Description of selected adverse reactions” below). The most common adverse reactions with avelumab were fatigue (30.0%), nausea (23.6%), diarrhoea (18.5%), constipation (18.1%), decreased appetite (17.6%), infusion-related reactions (15.9%), vomiting (15.6%), and weight decreased (14.5%). 10 The most common Grade ≥ 3 adverse reactions were anaemia (5.6%), hypertension (3.9%), hyponatraemia (3.6%), dyspnoea (3.5%), and abdominal pain (2.6%). Serious adverse reactions were immune-mediated adverse reactions and infusion-related reaction (see section 4.4). Tabulated list of adverse reactions The safety of avelumab as monotherapy has been evaluated in 2 082 patients with solid tumours including metastatic MCC or locally advanced or metastatic UC receiving 10 mg/kg every 2 weeks of avelumab in clinical studies or reported from post-marketing use of avelumab (see Table 2). These reactions are presented by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 2: Adverse reactions in patients treated with avelumab as monotherapy Frequency Adverse reactions Blood and lymphatic system disorders Very common Anaemia Common Lymphopenia, thrombocytopenia Uncommon Eosinophilia§ Not known Neutropenia* Immune system disorders Very common Infusion-related reaction# Uncommon Hypersensitivity, drug hypersensitivity Rare Anaphylactic reaction, Type I hypersensitivity, sarcoidosis* Endocrine disorders Common Hypothyroidism*, hyperthyroidism* Uncommon Adrenal insufficiency*, autoimmune thyroiditis*, thyroiditis*, autoimmune hypothyroidism* Rare Adrenocortical insufficiency acute*, hypopituitarism* Metabolism and nutrition disorders Very common Decreased appetite Commo

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HOS-098137 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098136 · has-indication-information · PDF-Seite 2

Bavencio is indicated as monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC). Bavencio is indicated as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. Bavencio in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) (see section 5.1).

HOS-098139 · has-interaction-information · PDF-Seite 9

No interaction studies have been conducted with avelumab. Avelumab is primarily metabolised through catabolic pathways, therefore, it is not expected that avelumab will have pharmacokinetic drug-drug interactions with other medicinal products. 9

HOS-098140 · has-pregnancy-information · PDF-Seite 10

Women of childbearing potential/Contraception Women of childbearing potential should be advised to avoid becoming pregnant while receiving avelumab and should use effective contraception during treatment with avelumab and for at least 1 month after the last dose of avelumab. Pregnancy There are no or limited data from the use of avelumab in pregnant women. Animal reproduction studies have not been conducted with avelumab. However, in murine models of pregnancy, blockade of PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in an increased foetal loss (see section 5.3). These results indicate a potential risk, based on its mechanism of action, that administration of avelumab during pregnancy could cause foetal harm, including increased rates of abortion or stillbirth. Human IgG1 immunoglobulins are known to cross the placental barrier. Therefore, avelumab has the potential to be transmitted from the mother to the developing foetus. It is not recommended to use avelumab during pregnancy unless the clinical condition of the woman requires treatment with avelumab. Breast-feeding It is unknown whether avelumab is excreted in human milk. Since it is known that antibodies can be secreted in human milk, a risk to the newborns/infants cannot be excluded. Breast-feeding women should be advised not to breast-feed during treatment and for at least 1 month after the last dose due to the potential for serious adverse reactions in breast-fed infants. Fertility The effect of avelumab on male and female fertility is unknown. Although studies to evaluate the effect of avelumab on fertility have not been conducted, there were no notable effects in the female reproductive organs in monkeys based on 1-month and 3-month repeat-dose toxicity studies (see section 5.3).

HOS-098138 · has-warning-information · PDF-Seite 5

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. Infusion-related reactions Infusion-related reactions, which might be severe, have been reported in patients receiving avelumab (see section 4.8). Patients should be monitored for signs and symptoms of infusion-related reactions including pyrexia, chills, flushing, hypotension, dyspnoea, wheezing, back pain, abdominal pain, and urticaria. For Grade 3 or Grade 4 infusion-related reactions, the infusion should be stopped and avelumab should be permanently discontinued (see section 4.2). 5 For Grade 1 infusion-related reactions, the infusion rate should be slowed by 50% for the current infusion. For patients with Grade 2 infusion-related reactions, the infusion should be temporary discontinued until Grade 1 or resolved, then the infusion will restart with a 50% slower infusion rate (see section 4.2). In case of recurrence of Grade 1 or Grade 2 infusion-related reaction, the patient may continue to receive avelumab under close monitoring, after appropriate infusion rate modification and premedication with paracetamol and antihistamine (see section 4.2). In patients treated with avelumab as monotherapy, 24.6% (513/2 082) of patients experienced infusion-related reactions. Of these, 97.7% (501/513) had a first infusion-related reaction during the first 4 infusions of which 2.7% (14/513) were Grade ≥ 3. In the remaining 2.3% (12/513) of patients, infusion-related reactions occurred after the first 4 infusions and 91.7% (11/12) were of Grade 1 or Grade 2. Immune-mediated adverse reactions Immune-mediated adverse reactions, which may be severe or fatal, can occur in one or multiple organ systems or tissues simultaneously in patients treated with avelumab. Institute medical management promptly, including specialty consultation as appropriate (see section 4.2), to address associated morbidity and risk of mortality. While immune-mediated adverse reactions usually occur during treatment, symptoms can also manifest after discontinuation. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of avelumab. Monitor patients for signs and symptoms of immune-mediated adverse reactions. Most immune-mediated adverse reactions with avelumab were reversible and managed with temporary or permanen

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