General: In order to improve the traceability of biological medicinal products, the trade name and batch number of the administered product should be clearly recorded (or stated) in the patient file.
All Indications: Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents including Actemra (see Adverse Reactions). Actemra treatment should not be initiated in patients with active infections. Administration of Actemra should be interrupted if a patient develops a serious infection until the infection is controlled. Healthcare professionals should exercise caution when considering the use of Actemra in patients with a history of recurring infection or with underlying conditions (e.g. diverticulitis, diabetes) which may predispose patients to infections.
Vigilance for the timely detection of serious infection is recommended for patients receiving immunosuppressive agents, such as Actemra, as signs and symptoms of acute inflammation may be lessened, due to suppression of the acute phase reactants. Patients (which include younger children who may be less able to communicate their symptoms) and parents/guardians of minors should be instructed to contact a healthcare professional immediately when any symptoms suggesting infection appear, in order to assure rapid evaluation and appropriate treatment.
Complications of diverticulitis: Events of diverticular perforation as complications of diverticulitis have been reported in patients treated with Actemra. Actemra 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, should be evaluated promptly for early identification of gastrointestinal perforation.
Tuberculosis: As recommended for other biologic therapies in all patients should be screened for latent tuberculosis infection prior to starting Actemra therapy. Patients with latent tuberculosis should be treated with standard anti-mycobacterial therapy before initiating Actemra.
Vaccinations: Live and live attenuated vaccines should not be given concurrently with Actemra 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 Actemra. In a randomized open-label study, adult RA patients treated with Actemra and MTX were able to mount an effective response to both the 23- valent pneumococcal polysaccharide and tetanus toxoid vaccines which was comparable to the response seen in patients on MTX only. The data demonstrated a small attenuation in the immune response to the 23-valent pneumococcal polysaccharide with ACT + MTX compared with MTX alone, but the response to tetanus toxoid vaccine in each treatment group was similar.
It is recommended that all patients, particularly pediatric or elderly patients, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating Actemra therapy. The interval between live vaccinations and initiation of Actemra therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis have been reported in association with Actemra (see Clinical Trials under Adverse Reactions). In the post marketing setting, events of serious hypersensitivity and anaphylaxis have occurred in patients treated with a range of doses of Actemra, with or without concomitant therapies, premedication, and / or a previous hypersensitivity reaction. In the post marketing setting, cases with a fatal outcome have been reported with intravenous Actemra. These events have occurred as early as the first infusion of Actemra (see Contraindications and Post Marketing Experience under Adverse Reactions). Appropriate treatment should be available for immediate use in the event of an anaphylactic reaction during infusion with Actemra. If an anaphylactic reaction or other serious hypersensitivity reaction occurs, administration of Actemra should be stopped immediately and Actemra should be permanently discontinued (see Dosage & Administration).
Active Hepatic Disease and Hepatic Impairment: Treatment with Actemra particularly when administered concomitantly with methotrexate, may be associated with elevations in hepatic transaminases (see Clinical Trials under Adverse Reactions). Therefore caution should be exercised when considering treatment of patients with active hepatic disease or hepatic impairment, as the safety of Actemra in these patients has not been adequately studied (see Special Dosage Instructions under Dosage & Administration).
Hepatotoxicity: Mild and moderate elevations of hepatic transaminases have been observed with Actemra treatment (see Clinical Trials under Adverse Reactions). Increased frequency of these elevations was observed when drugs), which are known to cause hepatotoxicity (e.g. methotrexate (MTX) were used in combination with Actemra.
Serious drug-induced liver injury, including acute liver failure, hepatitis and jaundice, have been observed with Actemra (see Post Marketing Experience under Adverse Reactions). Serious hepatic injury occurred between 2 weeks to more than 5 years after initiation of Actemra. Cases of liver failure resulting in liver transplantation have been reported.
Caution should be exercised when considering initiation of Actemra treatment in patients with elevated transaminases ALT or AST above 1.5x ULN. In patients with elevated ALT or AST above 5x ULN treatment is not recommended.
In RA, pJIA and SJIA, ALT/AST should be monitored every 4 to 8 weeks for the first 6 months of treatment followed by every 12 weeks thereafter. For recommended dose modifications, including Actemra discontinuation, based on transaminases levels, see Dosage & Administration.
Viral reactivation: Viral reactivation (e.g. hepatitis B virus) has been reported with biologic therapies for rheumatoid arthritis. In clinical studies with Actemra, patients who screened positive for hepatitis were excluded.
Demyelinating disorders: Physicians should be vigilant for symptoms potentially indicative of new onset central demyelinating disorders. The potential for central demyelination with Actemra is currently unknown.
Neutropenia: Treatment with Actemra was associated with a higher incidence of neutropenia. Treatment-related neutropenia was not associated with serious infection in clinical trials (see Clinical Trials under Adverse Reactions).
Caution should be exercised when considering initiation of Actemra treatment in patients with a low neutrophil count i.e. absolute neutrophil count (ANC) below 2 x 109/L. In patients with an absolute neutrophil count below 0.5 x 109/L treatment is not recommended.
In RA, the neutrophil count should be monitored 4 to 8 weeks after start of therapy and thereafter according to good clinical practice. For recommended dose modifications based on ANC results, see Dosage & Administration.
In pJIA and sJIA, the neutrophil count should be monitored at the time of the second infusion and thereafter according to good clinical practice (see Dose modifications under Dosage & Administration).
Thrombocytopenia: Treatment with Actemra was associated with a reduction in platelet counts. Treatment-related reduction in platelets was not associated with serious bleeding events in clinical trials (see Clinical Trials under Adverse Reactions).
Caution should be exercised when considering initiation of Actemra treatment in patients with a platelet count below 100 x 103/mL. In patients with a platelet count below 50 x 103/mL treatment is not recommended. In RA, platelets should be monitored 4 to 8 weeks after start of therapy and thereafter according to good clinical practice. For recommended dose modifications based on platelet counts, see Dosage and Administration. In pJIA and sJIA: Platelets should be monitored at the time of the second infusion and thereafter according to good clinical practice (see Dose modifications under Dosage & Administration).
Lipids parameters: Elevations of lipid parameters such as total cholesterol, triglycerides and/or low density lipoprotein (LDL) cholesterol have been observed (see Clinical Trials under Adverse Reactions).
In patients treated with Actemra, assessment of lipid parameters should be performed 4 to 8 weeks following initiation of Actemra therapy. Patients should be managed according to local clinical guidelines for management of hyperlipidaemia.
Cardiovascular risk: RA patients have an increased risk for cardiovascular disorders and should have risk factors (e.g. hypertension, hyperlipidaemia) managed as part of usual standard of care.
Combination with TNF antagonists: There is no experience with the use of Actemra with TNF antagonists or other biological treatments for RA. Actemra is not recommended for use with other biological agents.
Neurological disorders: Physicians should be vigilant for symptoms potentially indicative of new-onset central demyelinating disorders. The potential for central demyelination with Actemra is currently unknown.
Malignancy: The risk of malignancy is increased in patients with RA. Immunomodulatory medicinal products may increase the risk of malignancy.
Infusion reactions: Infusion reactions have been observed during and within 24 hours of treatment with Actemra.
Sodium: This medicinal product contains 1.17 mmol (or 26.55 mg) sodium per maximum dose of 1200 mg. To be taken into consideration by patients on a controlled sodium diet. Doses below 1025 mg of this medicinal product contain less than 1 mmol sodium (23 mg), i.e. essentially 'sodium free'.
Systemic juvenile idiopathic arthritis [IV formulation only]: Macrophage activation syndrome (MAS): MAS is a serious life-threatening disorder that may develop in patients with sJIA. In clinical trials, Actemra has not been studied in patients during an episode of active MAS.
Drug Abuse and Dependence: No studies on the effects on the potential for Actemra to cause dependence have been performed. However, there is no evidence from the available data that Actemra treatment results in dependence.
Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machine have been performed. However, there is no evidence from the available data that Actemra treatment affects the ability to drive and use machines.
Renal Impairment: See Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Use in Children: See Special Dosage Instructions under Dosage & Administration.
Use in the Elderly: See Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.