ROACTEMRA

Tocilizumab subcutaneous formulation is administered with a single-use pre-filled pen. Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA, sJIA, pJIA and/or GCA. The pre-filled pen should not be used to treat paediatric patients < 12 years of age since there is a potential risk of intramuscular injection due to thinner subcutaneous tissue layer.

The first injection should be performed under the supervision of a qualified health care professional. A patient or parent/guardian can inject this medicinal product only if the physician determines that it is appropriate and the patient or parent/guardian agrees to medical follow-up as necessary and has been trained in proper injection technique.

Patients who transition from tocilizumab intravenous therapy to subcutaneous administration should administer the first subcutaneous dose at the time of the next scheduled intravenous dose under the supervision of a qualified health care professional.

All patients treated with RoActemra must be given the Patient Card. Suitability of the patient or parent/guardian for subcutaneous home use should be assessed and patients or their parent/guardian should be instructed to inform a healthcare professional before administering the next dose if they experience symptoms of an allergic reaction.

4). Posology RA patients The recommended posology is subcutaneous 162 mg once every week. Limited information is available regarding switching patients from tocilizumab intravenous formulation to tocilizumab subcutaneous fixed dose formulation.

The once every week dosing interval should be followed. 3 gb-spc-roactemra-clean-251215-162mg-pen Patients transitioning from intravenous to subcutaneous formulation should administer their first subcutaneous dose instead of the next scheduled intravenous dose under the supervision of a qualified healthcare professional.

GCA patients The recommended posology is subcutaneous 162 mg once every week in combination with a tapering course of glucocorticoids. This medicinal product can be used alone following discontinuation of glucocorticoids. 4). Based upon the chronic nature of GCA, treatment beyond 52 weeks should be guided by disease activity, physician discretion, and patient choice.

4). • Liver enzyme abnormalities Laboratory Value Action > 1 to 3 × Upper Limit of Normal (ULN) Dose modify concomitant DMARDs (RA) or immunomodulatory agents (GCA) if appropriate. For persistent increases in this range, reduce tocilizumab dose frequency to every other week injection or interrupt treatment until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalised.

Restart with weekly or every other week injection, as clinically appropriate. > 3 to 5 × ULN Interrupt treatment dosing until < 3 × ULN and follow recommendations above for > 1 to 3 × ULN. ), discontinue treatment. > 5 × ULN Discontinue treatment.

• Low absolute neutrophil count (ANC) In patients not previously treated with tocilizumab, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 × 109/L. Laboratory Value (cells × 109/L ) Action ANC > 1 Maintain dose.

5 to 1 Interrupt tocilizumab dosing. When ANC increases > 1 × 109/L resume treatment dosing every other week and increase to every week injection, as clinically appropriate. 5 Discontinue treatment. • Low platelet count Laboratory Value (cells × 103/μL) Action 50 to 100 Interrupt tocilizumab dosing.

When platelet count > 100 × 103/μL resume treatment dosing every other week and increase to every week injection as clinically appropriate. < 50 Discontinue treatment. RA and GCA patients Missed dose If a patient misses a subcutaneous weekly injection of tocilizumab within 7 days of the scheduled dose, he/she should be instructed to take the missed dose on the next scheduled day.

If a patient misses a subcutaneous once every other week injection of tocilizumab within 7 days of the scheduled dose, he/she should be instructed to take the missed dose immediately and the next dose on the next scheduled day. Special populations Elderly No dose adjustment is required in elderly patients > 65 years of age.

Renal impairment No dose adjustment is required in patients with mild or moderate renal impairment. 2). Renal function must be monitored closely in these patients. Hepatic impairment Tocilizumab has not been studied in patients with hepatic impairment.

Therefore, no dose recommendations can be made. Paediatric population The safety and efficacy of tocilizumab subcutaneous formulation in children from birth to less than 1 year have not been established. No data are available. A change in dose should only be based on a consistent change in the patient’s body weight over time.

Tocilizumab can be used alone or in combination with MTX. sJIA patients The recommended posology in patients above 12 years of age is 162 mg subcutaneously once every week in patients weighing greater than or equal to 30 kg or 162 mg subcutaneously once every 2 weeks in patients weighing less than 30 kg.

The pre-filled pen should not be used to treat paediatric patients < 12 years of age. Patients must have a minimum body weight of 10 kg when receiving tocilizumab subcutaneously. 5 gb-spc-roactemra-clean-251215-162mg-pen pJIA patients The recommended posology in patients above 12 years of age is 162 mg subcutaneously once every 2 weeks in patients weighing greater than or equal to 30 kg or 162 mg […]

Summary of the safety profile The safety profile comes from 4510 patients exposed to tocilizumab in clinical trials; the majority of these patients were participating in RA studies (n=4009), while the remaining experience comes from GCA (n=149), pJIA (n=240) and sJIA (n=112) studies.

The safety profile of tocilizumab across these indications remains similar and undifferentiated. The most commonly reported adverse reactions were upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased ALT.

The most serious adverse reactions were serious infections, complications of diverticulitis, and hypersensitivity reactions. 12 gb-spc-roactemra-clean-251215-162mg-pen Tabulated list of adverse reactions Adverse reactions from clinical trials and/or post-marketing experience with tocilizumab based on spontaneous case reports, literature cases and cases from non-interventional study programs are listed in Table 1 and are presented by MedDRA system organ class.

The corresponding frequency category is based on 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) or very rare (<1/10,000), and frequency not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 13 gb-spc-roactemra-clean-251215-162mg-pen Table 1. 4 3 This adverse reaction was identified through post-marketing surveillance but not observed in controlled clinical trials.

The frequency category was estimated as the upper limit of the 95% confidence interval calculated on the basis of the total number of patients exposed to TCZ in clinical trials. Description of selected adverse reactions (subcutaneous use) RA patients The safety of subcutaneous tocilizumab in RA includes a double-blind, controlled, multicentre study, SC-I.

SC-I was a non-inferiority study that compared the efficacy and safety of 162 mg administered every week versus 8 mg/kg intravenous in 1262 patients with RA. All patients received background non-biologic DMARD(s). The safety and immunogenicity observed for tocilizumab administered subcutaneous was consistent with the known safety profile of intravenous tocilizumab and no new or unexpected adverse reactions were observed (see Table 1).

A higher frequency of injection site reactions was observed in the subcutaneous arms compared with placebo subcutaneous injections in the intravenous arms. 4% (15/631) for the subcutaneous tocilizumab and the subcutaneous placebo (intravenous group) weekly injections, respectively.

These injection site reactions (including erythema, pruritus, pain and haematoma) were mild to moderate in severity. The majority was resolved without any treatment and none necessitated treatment discontinuation. Immunogenicity In SC-I, a total of 625 patients treated with tocilizumab 162 mg weekly were tested for anti- tocilizumab antibodies in the 6 month controlled period.

8%) developed positive anti-tocilizumab antibodies; of these, all developed neutralising anti-tocilizumab antibodies. 2%). In SC-II, a total of 434 patients treated with tocilizumab 162 mg every other week were tested for anti-tocilizumab antibodies in the 6 month controlled period.

4%) developed neutralising anti- tocilizumab antibodies. 9%). No correlation of antibody development to clinical response or adverse events was observed. 9% of patients on the subcutaneous weekly dose. There was no clear relationship between decreases in neutrophils below 1 × 109/L and the occurrence of serious infections.

Platelets During routine laboratory monitoring in the tocilizumab 6 month clinical trial SC-I, none of the patients on the subcutaneous weekly dose had a decrease in platelet count to ≤ 50 × 103/μL. 4% of […]

RoActemra subcutaneous formulation is not intended for intravenous administration. RoActemra subcutaneous formulation is not intended to be given to children with sJIA weighing less than 10 kg. 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, Undesirable effects). 3). 8). g. diverticulitis, diabetes and interstitial lung disease which may predispose patients to infections. Vigilance for the timely detection of serious infection is recommended for patients receiving immunosuppressive agents such as tocilizumab as signs and symptoms of acute inflammation may be lessened, due to suppression of the acute phase reactants.

The effects of tocilizumab on C-reactive protein (CRP), neutrophils and signs and symptoms of infection must be considered when evaluating a patient for a potential infection. Patients, (which includes younger children with sJIA or pJIA who may be less able to communicate their symptoms) and parents/guardians of sJIA or pJIA patients, should be instructed to contact their healthcare professional immediately when any symptoms suggesting infection appear, in order to assure rapid evaluation and appropriate treatment.

Tuberculosis As recommended for other biological treatments, all patients should be screened for latent tuberculosis (TB) infection prior to starting tocilizumab therapy. Patients with latent TB must be treated with standard anti-mycobacterial therapy before initiating treatment.

Prescribers 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. , persistent cough, wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after therapy with this medicinal product.

g. hepatitis B virus) has been reported with biologic therapies for RA. In clinical trials with tocilizumab, patients who screened positive for hepatitis were excluded. 8). This medicinal product should be used with caution in patients with previous history of intestinal ulceration or diverticulitis.

Patients presenting with symptoms potentially indicative of complicated diverticulitis, such as abdominal pain, haemorrhage and/or unexplained change in bowel habits with fever must be evaluated promptly for early identification of diverticulitis which can be associated with gastrointestinal perforation.

8). Such reactions may be more severe, and potentially fatal in patients who have experienced hypersensitivity reactions during previous treatment with tocilizumab even if they have received premedication with steroids and antihistamines.

If an anaphylactic reaction or other serious hypersensitivity reaction occurs, administration of tocilizumab must be stopped immediately, appropriate therapy initiated and treatment should be permanently discontinued. 8). 8). g. MTX) were used in combination with tocilizumab.

When clinically indicated, other liver function tests including bilirubin should be considered. 8). Serious hepatic injury occurred between 2 weeks to more than 5 years after initiation of treatment. Cases of liver failure resulting in liver transplantation have been reported.

Patients must be advised to immediately seek medical help if they experience signs and symptoms of hepatic injury. 5 × ULN. In patients with baseline ALT or AST > 5 × ULN, treatment is not recommended. In RA, GCA, pJIA and sJIA patients, ALT/AST should be monitored every 4 to 8 weeks for the first 6 months of treatment followed by every 12 weeks thereafter.

2. For ALT or AST elevations > 3–5 × ULN, treatment should be interrupted. Haematological abnormalities Decreases in neutrophil and platelet counts have occurred following treatment with tocilizumab 8 mg/kg in combination with MTX (see section […]

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