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 of the administered product should be clearly recorded. It is recommended to record the batch number as well.

Serious infections
Patients should be closely monitored for the development of signs and symptoms of infection during treatment with sarilumab (see sections 4.2 and 4.8). As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Sarilumab should not be administered in patients with an active infection, including localised infections. The risks and benefits should be considered prior to initiating treatment in patients who have:
•      chronic or recurrent infection;
•      a history of serious or opportunistic infections;
•      HIV infection;
•      underlying conditions that may predispose them to infection;
•      been exposed to tuberculosis; or
•      lived in or travelled to areas of endemic tuberculosis or endemic mycoses.

Treatment with sarilumab should be withheld if a patient develops a serious infection or an opportunistic infection.

A patient who develops an infection during treatment should also undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including sarilumab. The most frequently observed serious infections with sarilumab included pneumonia and cellulitis (see section 4.8). Among opportunistic infections, tuberculosis, candidiasis, and pneumocystis were reported with sarilumab. In isolated cases, disseminated rather than localised infections were observed in patients often taking concomitant immunosuppressants such as MTX or corticosteroids.

Tuberculosis
Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating treatment with sarilumab. Patients with latent or active tuberculosis should be treated with standard antimycobacterial therapy before initiating treatment. Anti-tuberculosis therapy should be considered prior to initiation of treatment in patients with a past medical history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. When considering anti-tuberculosis therapy, consultation with a physician with expertise in tuberculosis may be appropriate.

Patients should be closely monitored for the development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Viral reactivation
Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with sarilumab (see section 4.8). No cases of Hepatitis B reactivation were reported in the clinical studies; however patients who were at risk for reactivation were excluded.

Laboratory parameters
Neutrophil count
Treatment with sarilumab was associated with a higher incidence of decrease in ANC (see section 4.8). Decrease in ANC was not associated with higher incidence of infections, including serious infections.
• Initiating treatment with sarilumab is not recommended in patients with a low neutrophil count, i.e., ANC less than 2 x 109/L. In patients who develop an ANC less than 0.5 x 109/L, treatment with sarilumab should be discontinued (see section 4.2).
• Neutrophil count should be monitored 4 to 8 weeks after start of therapy and according to clinical judgment thereafter. For recommended dose modifications based on ANC results, see section 4.2.
• Based on the pharmacodynamics of the changes in ANC, results obtained at the end of the dosing interval should be used when considering dose modification (see section 5.1).

Platelet count
Treatment with sarilumab was associated with a reduction in platelet counts in clinical studies.
Reduction in platelets was not associated with bleeding events (see section 4.8).
• Initiating treatment with sarilumabis not recommended in patients with a platelet count below 150 x103/µL. In patients who develop a platelet count less than 50 x 103/ µL, treatment with sarilumab should be discontinued.
• Platelet count should be monitored 4 to 8 weeks after start of therapy and according to clinical judgment thereafter. For recommended dose modifications based on platelet counts, see section 4.2.

Liver enzymes
Treatment with sarilumab was associated with a higher incidence of transaminase elevations. These elevations were transient and did not result in any clinically evident hepatic injury in clinical studies (see section 4.8). Increased frequency and magnitude of these elevations were observed when potentially hepatotoxic medicinal products (e.g., MTX) were used in combination with sarilumab.

Initiating treatment with sarilumab is not recommended in patients with elevated transaminases, ALT or AST greater than 1.5 x ULN. In patients who develop elevated ALT greater than 5 x ULN, treatment with sarilumab should be discontinued (see section 4.2).

ALT and AST levels should be monitored 4 to 8 weeks after start of therapy and every 3 months thereafter. When clinically indicated, consider other liver function tests such as bilirubin. For recommended dose modifications based on transaminase elevations, see section 4.2.

Lipid abnormalities
Lipid levels may be reduced in patients with chronic inflammation. Treatment with sarilumab was associated with increases in lipid parameters such as LDL cholesterol, HDL cholesterol, and/or triglycerides (see section 4.8).

Lipid parameters should be assessed approximately 4 to 8 weeks following initiation of treatment with sarilumab, then at approximately 6 month intervals.
Patients should be managed according to clinical guidelines for the management of hyperlipidaemia.

Gastrointestinal perforation and diverticulitis
Cases of gastrointestinal perforation and diverticulitis have been reported in association with sarilumab. Gastrointestinal perforation has been reported in patients with and without diverticulitis.
Sarilumab should be used with caution in patients with previous history of intestinal ulceration or diverticulitis. Patients presenting with new onset abdominal symptoms such as persistent pain with fever should be evaluated promptly (see section 4.8).

Malignancies
Treatment with immunosuppressants may result in an increased risk of malignancies. The impact of treatment with sarilumab on the development of malignancies is not known but malignancies were reported in clinical studies (see section 4.8).

Hypersensitivity reactions
Hypersensitivity reactions have been reported in association with sarilumab (see section 4.8). Injection site rash, rash, and urticaria were the most frequent hypersensitivity reactions. Patients should be advised to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, administration of sarilumab should be stopped immediately (see section 4.3).

Hepatic impairment
Treatment with sarilumab is not recommended in patients with active hepatic disease or hepatic impairment (see sections 4.2 and 4.8).

Vaccinations
Concurrent use of live vaccines as well as live attenuated vaccines should be avoided during treatment with sarilumab as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving sarilumab. Prior to initiating treatment, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines. The interval between live vaccinations and initiation of therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents (see section 4.5).

Cardiovascular risk
RA patients have an increased risk for cardiovascular disorders and risk factors (e.g. hypertension, hyperlipidaemia) should be managed as part of usual standard of care.

Effects on Driving

4.7   Effects on ability to drive and use machines

Kevzara has no or negligible influence on the ability to drive and use machines.