Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
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-mediated adverse reactions
Severe and fatal immune-mediated adverse reactions have been observed with cemiplimab (see section 4.2 and section 4.8). These immune-mediated reactions may involve any organ system. Immune-mediated reactions can manifest at any time during treatment with cemiplimab; however, immune-mediated adverse reactions can occur after discontinuation of cemiplimab.

Immune-mediated adverse reactions affecting more than one body system can occur simultaneously, such as myositis and myocarditis or myasthenia gravis, in patients treated with cemiplimab or other PD-1/PD-L1 inhibitors.

Monitor patients for signs and symptoms of immune-mediated adverse reactions. Immune-mediated adverse reactions should be managed with cemiplimab treatment modifications, hormone replacement therapy (if clinically indicated), and corticosteroids. For suspected immune-mediated adverse reactions, patients should be evaluated to confirm an immune-mediated adverse reaction and to exclude other possible causes, including infection. Depending upon the severity of the adverse reaction, cemiplimab should be withheld or permanently discontinued (see section 4.2).

Immune-mediated pneumonitis
Immune-mediated pneumonitis, defined as requiring use of corticosteroids with no clear alternate aetiology, including fatal cases, has been observed in patients receiving cemiplimab (see section 4.8).
Patients should be monitored for signs and symptoms of pneumonitis and causes other than immune- mediated pneumonitis should be ruled out. Patients with suspected pneumonitis should be evaluated with radiographic imaging as indicated based on clinical evaluation and managed with cemiplimab treatment modifications and corticosteroids (see section 4.2).

Immune-mediated colitis
Immune-mediated diarrhoea or colitis, defined as requiring use of corticosteroids with no clear alternate aetiology, has been observed in patients receiving cemiplimab (see section 4.8). Patients should be monitored for signs and symptoms of diarrhoea or colitis and managed with cemiplimab treatment modifications, anti-diarrhoeal agents, and corticosteroids (see section 4.2).

Immune-mediated hepatitis
Immune-mediated hepatitis, defined as requiring use of corticosteroids with no clear alternate aetiology, including fatal cases, has been observed in patients receiving cemiplimab (see section 4.8). Patients should be monitored for abnormal liver tests prior to and periodically during treatment as indicated based on clinical evaluation and managed with cemiplimab treatment modifications and corticosteroids (see section 4.2).

Immune-mediated endocrinopathies
Immune-mediated endocrinopathies, defined as treatment-emergent endocrinopathies with no clear alternate aetiology, have been observed in patients receiving cemiplimab (see section 4.8).

Thyroid disorders (Hypothyroidism/Hyperthyroidism/Thyroiditis)
Immune-mediated thyroid disorders have been observed in patients receiving cemiplimab. Thyroiditis can present with or without an alteration in thyroid function tests. Hypothyroidism can follow hyperthyroidism. Thyroid disorders can occur at any time during the treatment. Patients should be monitored for changes in thyroid function at the start of treatment and periodically during the treatment as indicated based on clinical evaluation (see section 4.8). Patients should be managed with hormone replacement therapy (if indicated) and cemiplimab treatment modifications. Hyperthyroidism should be managed according to standard medical practice (see section 4.2).

Hypophysitis
Immune-mediated hypophysitis has been observed in patients receiving cemiplimab (see section 4.8).
Patients should be monitored for signs and symptoms of hypophysitis and managed with cemiplimab treatment modifications, corticosteroids and hormone replacement, as clinically indicated (see section 4.2).

Adrenal insufficiency
Adrenal insufficiency has been observed in patients receiving cemiplimab (see section 4.8). Patients should be monitored for signs and symptoms of adrenal insufficiency during and after treatment and managed with cemiplimab treatment modifications, corticosteroids and hormone replacement, as clinically indicated (see section 4.2).

Type 1 Diabetes mellitus
Immune-mediated type 1 diabetes mellitus, including diabetic ketoacidosis, has been observed in patients receiving cemiplimab (see section 4.8). Patients should be monitored for hyperglycaemia and signs and symptoms of diabetes as indicated based on clinical evaluation and managed with oral anti-hyperglycaemics or insulin and cemiplimab treatment modifications (see section 4.2).

Immune-mediated skin adverse reactions
Immune-mediated skin adverse reactions, defined as requiring use of systemic corticosteroids with no clear alternate aetiology, including severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (some cases with fatal outcome), and other skin reactions such as rash, erythema multiforme, pemphigoid, have been reported in association with cemiplimab treatment (see section 4.8).

Patients should be monitored for evidence of suspected severe skin reactions and exclude other causes.
Patients should be managed with cemiplimab treatment modifications and corticosteroids (see section 4.2). For symptoms or signs of SJS or TEN, refer the patient for specialised care for assessment and treatment and manage patient with treatment modifications (see section 4.2).

Cases of SJS, fatal TEN and stomatitis occurred following 1 dose of cemiplimab in patients with prior exposure to idelalisib, who were participating in a clinical trial evaluating cemiplimab in Non-Hodgkin Lymphoma (NHL), and who had recent exposure to sulfa containing antibiotics (see section 4.8).
Patients should be managed with cemiplimab treatment modifications and corticosteroids as described above (see section 4.2).

Immune-mediated nephritis
Immune-mediated nephritis, defined as requiring use of corticosteroids with no clear alternate aetiology, including a fatal case, has been observed in patients receiving cemiplimab (see section 4.8). Monitor patients for changes in renal function. Patients should be managed with cemiplimab treatment modifications and corticosteroids (see section 4.2).

Other immune-mediated adverse reactions
Other fatal and life-threatening immune-mediated adverse reactions have been observed in patients receiving cemiplimab including paraneoplastic encephalomyelitis, meningitis myositis and myocarditis (see section 4.8 for other immune-mediated adverse reactions).

Noninfective cystitis has been reported with other PD-1/PD-L1 inhibitors.
Evaluate suspected immune-mediated adverse reactions to exclude other causes. Patients should be monitored for signs and symptoms of immune-mediated adverse reactions and managed with cemiplimab treatment modifications and corticosteroids as clinically indicated (see section 4.2 and section 4.8).

Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with PD-1 inhibitors. Treatment with cemiplimab may increase the risk of rejection in solid organ transplant recipients. The benefit of treatment with cemiplimab versus the risk of possible organ rejection should be considered in these patients. Cases of graft-versus-host disease have been reported in the post-marketing setting in patients treated with other PD-1/PD-L1 inhibitors in association with allogeneic haematopoietic stem cell transplant.

Haemophagocytic lymphohistiocytosis (HLH) has been reported in patients receiving cemiplimab (see section 4.8). Patients should be monitored for clinical signs and symptoms of HLH. If HLH is confirmed,
administration of cemiplimab should be discontinued and treatment for HLH initiated (see section 4.2).

Infusion-related reactions
Cemiplimab can cause severe or life-threatening infusion-related reactions (see section 4.8). Patients should be monitored for signs and symptoms of infusion-related reactions and managed with cemiplimab treatment modifications and corticosteroids. Cemiplimab should be interrupted or the rate of infusion slowed for mild or moderate infusion-related reactions. The infusion should be stopped and cemiplimab should be permanently discontinued for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions (see section 4.2).

Patients excluded from clinical studies
Patients that had active infections, were immunocompromised, had a history of autoimmune diseases, ECOG PS ≥2 or a history of interstitial lung disease were not included. For a full list of patients excluded from clinical studies, see section 5.1.

In the absence of data, cemiplimab should be used with caution in these populations after careful evaluation of the balance of benefits and risks for the patient.

Effects on Driving

4.7 Effects on ability to drive and use machines

Cemiplimab has no or negligible influence on the ability to drive and use machines. Fatigue has been reported following treatment with cemiplimab (see section 4.8).