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1). Patients must be given the patient card. Posology Rheumatoid arthritis The recommended dose of sarilumab is 200 mg once every 2 weeks administered as a subcutaneous injection. Polymyalgia rheumatica The recommended dose of sarilumab is 200 mg once every 2 weeks administered as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids, after which sarilumab can be continued as monotherapy.

Data are available in patients that were treated for up to 1 year. Therefore treatment beyond 52 weeks should be guided by disease activity, physician discretion, and patient choice. Dose modification Rheumatoid arthritis Reduction of dose from 200 mg once every 2 weeks to 150 mg once every 2 weeks is recommended for management of neutropenia, thrombocytopenia, and liver enzyme elevations.

Treatment with sarilumab must be withheld in patients who develop a serious infection until the infection is controlled. e. absolute neutrophil count (ANC) less than 2 x 109/L. Initiating treatment with sarilumab is not recommended in patients with a platelet count below 150 x 103/μL.

1) Lab Value (cells x 109/L) Recommendation ANC greater than 1 Current dose of sarilumab to be maintained. 5-1 Treatment with sarilumab to be withheld until >1 x 109/L. Sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate.

5 Treatment with sarilumab to be discontinued. Low Platelet Count Lab Value (cells x 103/μL) Recommendation 50 to 100 Treatment with sarilumab to be withheld until >100 x 103/μL. Sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate.

Less than 50 If confirmed by repeat testing, treatment with sarilumab to be discontinued. Liver Enzyme Abnormalities Lab Value Recommendation ALT > 1 to 3 x Upper Limit of Normal (ULN) Clinically appropriate dose modification of concomitant DMARDs or immunomodulatory agents to be considered.

ALT > 3 to 5 x ULN Treatment with sarilumab to be withheld until <3 x ULN. Sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate. ALT > 5 x ULN Treatment with sarilumab to be discontinued.

1): o neutropenia (ANC below 1 x 109/L at the end of the dosing interval) o thrombocytopenia (platelet count below 100 x 103 μL) o AST or ALT elevations (3 times above the ULN) Dosage modifications have not been studied in patients with PMR with these conditions.

For treatment initiation criteria, refer to the posology for PMR. Missed dose If a dose of sarilumab is missed and it has been 3 days or less since the missed dose, the next dose should be administered as soon as possible. The subsequent dose should be administered at the regularly scheduled time.

If it has been 4 days or more since the missed dose, the subsequent dose should be administered at the next regularly scheduled time, the dose should not be doubled. Special populations Renal impairment No dose adjustment is required in patients with mild to moderate renal impairment.

2). 4). 4). Paediatric population The safety and efficacy of sarilumab pre-filled syringe and pre-filled pen in children less than 18 years of age have not been established. No data are available. Method of administration Subcutaneous use.

Injection sites (abdomen, thigh and upper arm) should be rotated with each injection. Sarilumab should not be injected into skin that is tender, damaged, or has bruises or scars. 14 ml) of the pre-filled pen should be administered as a subcutaneous injection.

For the pre-filled pen, a patient may self-inject sarilumab or the patient's caregiver may administer sarilumab if their healthcare professional determines that it is appropriate. Proper training should be provided to patients and/or caregivers on the preparation and administration of sarilumab prior to use.

The pre-filled pen has not been studied in paediatric patients. Comprehensive instructions for administration of this medicinal product are given in the package leaflet.

0%). 4). Tabulated list of adverse reactions Adverse reactions listed in the table have been reported in controlled clinical studies. The frequency of adverse reactions listed below is defined using the following convention: 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 order of decreasing seriousness.

Table 2:

Adverse reactions in patients with RA and PMR MedDRA System Organ Class Frequency Adverse reaction Upper respiratory tract infection Urinary tract infection Oral herpes Cellulitis Pneumonia Nasopharyngitis Infections and infestations Common Diverticulitis Very common Neutropenia* Leukopenia* Blood and lymphatic system disorders Thrombocytopenia HypertriglyceridemiaMetabolism and nutrition disorders Common Hypercholesterolemia Gastrointestinal disorders Rare Gastrointestinal perforation Hepatobiliary disorders Common Transaminases increased Injection site erythemaGeneral disorders and administration site conditions Common Injection site pruritus* *In the SAPHYR study, the reported ADRs in PMR patients are neutropenia, leukopenia and injection site pruritus.

1 events per 100 patient-years, in the 200 mg and 150 mg sarilumab + DMARDs and placebo + DMARDs groups respectively. The most commonly reported infections (5% to 7% of patients) were upper respiratory tract infections, urinary tract infections, and nasopharyngitis.

1 events per 100 patient-years, in the 200 mg, 150 mg sarilumab + DMARDs, and placebo + DMARDs groups, respectively. 4 events per 100-patient years, respectively. The most frequently observed serious infections included pneumonia and cellulitis.

4). The overall rates of infections and serious infections in the sarilumab monotherapy population were consistent with rates in the sarilumab + DMARDs population. Gastrointestinal perforation Gastrointestinal perforation was reported in patients with and without diverticulitis.

Most patients who developed gastrointestinal perforations were taking concomitant nonsteroidal anti-inflammatory medicinal products (NSAIDs), corticosteroids, or MTX. 4). 2%). The rates of discontinuations due to hypersensitivity in the sarilumab + DMARDs long-term safety population and the sarilumab monotherapy population were consistent with the placebo-controlled population.

2% of the patients treated with sarilumab 200 mg every two weeks (q2w) + DMARD reported serious adverse reactions of hypersensitivity reactions, and none from sarilumab 150 mg q2w + DMARD group. 4% of patients receiving sarilumab 200 mg, 150 mg, and placebo respectively.

5%, 100%, and 100%, for sarilumab 200 mg, 150 mg, and placebo respectively). 2%) discontinued treatment due to injection site reactions. Laboratory abnormalities To allow for a direct comparison of frequency of laboratory abnormalities between placebo and active treatment, data from weeks 0-12 were used as this was prior to patients being permitted to switch from placebo to sarilumab.

6% of patients in the 200 mg and 150 mg sarilumab + DMARDs group, respectively, compared to no patients in the placebo + DMARDs group. 6% of patients in the 200 mg and 150 mg sarilumab + DMARDs groups, respectively. 2). Decrease in ANC was not associated with higher incidence of infections, including serious infections.

4). 6% of patients on 200 mg and 150 mg sarilumab + DMARDs, respectively, compared to no patients on placebo + DMARDs. In the sarilumab + DMARDs long-term safety population and the sarilumab monotherapy population, the observations on platelet counts were consistent with those seen in the placebo-controlled population.

There were no bleeding events associated with decreases in platelet count. […]

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. 8). As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Sarilumab must 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 must be withheld if a patient develops a serious infection or an opportunistic infection. Once the infection is controlled, treatment with sarilumab may be re-initiated at the discretion of the healthcare professional.

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. 8). Among opportunistic infections, tuberculosis, candidiasis, and pneumocystis were reported with sarilumab in RA.

In some patients with RA with concomitant tuberculosis, disseminated rather than localised infections were observed, most of whom were taking concomitant immunosuppressants such as MTX or corticosteroids, which may increase the risk of infection.

Tuberculosis Patients must be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating treatment with sarilumab. Patients with latent or active tuberculosis must be treated with standard antimycobacterial therapy before initiating treatment.

Anti-tuberculosis therapy must 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.

Healthcare professionals are reminded of the risk of false negative tuberculin skin and interferon-gamma TB blood test results, especially in patients who are severely ill or immunocompromised. 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.

8). No cases of Hepatitis B reactivation were reported in the clinical studies; however, patients who were at risk for reactivation were excluded. 8). Decrease in ANC was not associated with higher incidence of infections, including serious infections.

, ANC less than 2 x 109/L. 2). • Neutrophil count must be monitored 4 to 8 weeks after start of therapy and according to clinical judgment thereafter. 2. 1). Platelet count Treatment with sarilumab was associated with a reduction in platelet counts in clinical studies.

8). • Initiating treatment with sarilumab is 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 must be discontinued. • Platelet count must be monitored 4 to 8 weeks after start of therapy and according to clinical judgment thereafter.

2. Liver enzymes Treatment with sarilumab was associated with a higher incidence of transaminase elevations. 8). , MTX) were used in combination with sarilumab. 5 x ULN. 2). ALT and AST levels must 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 […]

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