Loqtorzi · 4.4 Special warnings and precautions for use · 1

HOS-100574 · has-adverse-reaction-information · PDF-Seite 9

Summary of the safety profile Toripalimab in combination with platinum containing chemotherapy (see section 4.2) The safety of toripalimab in combination with platinum containing chemotherapy has been evaluated in 403 patients with NPC or oesophageal squamous cell carcinoma (OSCC) receiving 240 mg toripalimab every 3 weeks in JUPITER-02 or JUPITER-06. The median duration of treatment in these patients was 6.5 months (range 1 day-2.1 years). The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. In this patient population, the most frequent adverse reactions were anaemia (44.9%), leukopenia (41.7%), neutropenia (39.0%), thrombocytopenia (30.3%), nausea (29.8%), vomiting (27.3%), decreased appetite (23.8%), rash (23.8%), fatigue (23.6%), liver function test abnormal (22.3%), hypothyroidism (18.4%), constipation (16.6%), neuropathy (15.1%), colitis (14.1%), pyrexia (13.6%), cough (11.4%), pruritus (11.4%), creatinine renal clearance decreased (11.2%), and hyponatraemia (10.2%). Incidences of grades 3-5 adverse reactions in patients with NPC were 81.5% for toripalimab combination therapy and 83.9% for chemotherapy alone and in patients with OSCC were 24.9% for toripalimab combination therapy and 13.6% for chemotherapy alone. Tabulated list of adverse reactions Adverse reactions observed in clinical studies of toripalimab as monotherapy or in combination with chemotherapy are listed in Table 2. Adverse reactions are presented by system organ class and by 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 includes only treatment related adverse drug reactions. The adverse reaction frequencies from clinical studies are based on all-cause adverse event frequencies, where a proportion of the events for 9 an adverse reaction may have other causes than the medicinal product such as the disease, other medicines or unrelated causes. Adverse reactions reported in clinical studies are listed by system organ class and by frequency. The safety data is based on 1 514 patients exposed to toripalimab (of which 1 100 patients were expo

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100570 · has-contraindication-information · PDF-Seite 5

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

HOS-100569 · has-indication-information · PDF-Seite 2

LOQTORZI, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma. LOQTORZI, in combination with cisplatin and paclitaxel, is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma.

HOS-100572 · has-interaction-information · PDF-Seite 8

No formal interaction studies have been performed. Since toripalimab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. Toripalimab is not a substrate for cytochrome P450 or active substance transporters. Toripalimab is not a cytokine and is unlikely to be a cytokine modulator. Additionally, pharmacokinetic (PK) interaction of toripalimab with small molecule active substances is not expected. There is no evidence of interaction mediated by non-specific clearance of lysosome degradation for antibodies. The use of systemic corticosteroids or immunosuppressants before starting toripalimab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of toripalimab. However, systemic corticosteroids or other immunosuppressants can be used after starting toripalimab to treat immune-related adverse reactions (see section 4.4). Corticosteroids can also be used as premedication, when toripalimab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions.

HOS-100573 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception Women of childbearing potential should use effective contraception during treatment with toripalimab and for at least 4 months after the last dose of toripalimab. 8 Pregnancy There are no data on the use of toripalimab in pregnant women. Animal studies have not been conducted with toripalimab; however, animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-related rejection of the developing foetus and result in foetal death (see section 5.3). Human immunoglobulin G4 (IgG4) is known to cross the placental barrier; therefore, toripalimab can potentially be transmitted from the mother to the developing foetus. Toripalimab should not be used during pregnancy or in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk. Breast-feeding It is unknown whether toripalimab is secreted in human milk. It is known that antibodies (including IgG4) are secreted in human milk; a risk to the breast-feeding newborn/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from toripalimab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. If a woman chooses to be treated with toripalimab, she should be instructed not to breast-feed while receiving toripalimab and for at least 4 months after the last dose of toripalimab. Fertility Studies to evaluate the effect of toripalimab on fertility have not been performed (see section 5.3).

HOS-100571 · 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. Immune-related adverse reactions Immune-related adverse reactions, which may be severe or fatal, can occur in patients treated with antibodies blocking the programmed cell death protein-1 / programmed death-ligand 1 (PD-1/PD-L1) pathway, including toripalimab. While immune-related adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, symptoms can also manifest after discontinuation of treatment. Immune-related adverse reactions may occur in any organ or tissue and may affect more than one body system simultaneously. Important immune-related adverse reactions listed in this section are not inclusive of all possible severe and fatal immune-related reactions. Early identification and management of immune-related adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Patients should be monitored closely for symptoms and signs of immune-related adverse reactions. Clinical chemistries including liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically during treatment. In cases of suspected immune-related adverse reactions, appropriate workup should be initiated to exclude alternative aetiologies, including infection. Medical management should be instituted promptly, including specialty consultation as appropriate. Toripalimab should be withheld or permanently discontinued depending on the type and severity of the adverse reaction (see section 4.2). If treatment with toripalimab should be withheld or permanently discontinued, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. If myocarditis is suspected, initiate high-dose steroids (e.g., methylprednisolone 1 g/day intravenously for 3–5 days). Upon improvement to Grade 1 or less, initiate corticosteroid taper. Consider administration of other systemic immunosuppressants in patients whose immune-related adverse reactions are not controlled with corticosteroid therapy. Hormone replacement therapy for endocrinopathies should be instituted as warranted. Treatment with toripalimab may be restarted within 12 weeks after last dose of toripalimab if the adverse reaction recovers to Grade ≤1 and corticosteroid dose has been reduced to ≤ 10 mg prednisone or equivalent per day.

Auszug; vollständigen Abschnitt im Original lesen.