Indicated for:

Rheumatoid Arthritis (RA) (adult patients):

• The treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

ACTEMRA may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion or as a subcutaneous injection.

Giant Cell Arteritis (GCA) (adult patients):

• The treatment of giant cell arteritis (GCA) in adult patients.

ACTEMRA can be used alone following discontinuation of glucocorticoids.

Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia.

Intravenous administration is not approved for GCA.

Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD) (adult patients):

• Slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease.

Interruption of dosing may be needed for management of dose-related laboratory abnormalities including
elevated liver enzymes, neutropenia, and thrombocytopenia.

Subcutaneous administration with the prefilled ACTPen autoinjector has not been studied in SSc-ILD.

Intravenous administration is not approved for SSc-ILD.

Polyarticular Juvenile Idiopathic Arthritis (PJIA) (pediatric patients 2 years of age and older):

• The treatment of active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.

ACTEMRA may be used alone or in combination with methotrexate.

Do not change dose based solely on a single visit body weight measurement, as weight may fluctuate.

Systemic Juvenile Idiopathic Arthritis (SJIA): (pediatric patients 2 years of age and older):

• The treatment of active systemic juvenile idiopathic arthritis in patients 2 years of age and older.

ACTEMRA may be used as an intravenous infusion or as a subcutaneous injection alone or in combination with methotrexate.

Do not change a dose based solely on a single visit body weight measurement, as weight may fluctuate.

Cytokine Release Syndrome (CRS) (adult and pediatric patients 2 years of age and older):

• The treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

Doses exceeding 800 mg per infusion are not recommended in CRS patients.

Subcutaneous administration is not approved for CRS.

Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt ACTEMRA until the infection is controlled. Reported infections include:

• Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before ACTEMRA use and during therapy. Treatment for latent infection should be initiated prior to ACTEMRA use
• Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease
• Bacterial, viral and other infections due to opportunistic pathogens. The risks and benefits of treatment with ACTEMRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection

Patients should be tested for latent tuberculosis before ACTEMRA use and during therapy. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ACTEMRA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Hold ACTEMRA if a patient develops a serious infection, an opportunistic infection, or sepsis.

A patient who develops a new infection during treatment with ACTEMRA should undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor the patient.

Do not administer ACTEMRA in patients with an active infection, including localized infections. The risks and benefits of treatment should be considered prior to initiating ACTEMRA in patients:
• with chronic or recurrent infection
• who have been exposed to tuberculosis
• with a history of serious or an opportunistic infection
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses or
• with underlying conditions that may predispose them to infection

Viral reactivation has been reported with immunosuppressive biologic therapies and cases of herpes zoster exacerbation were observed in clinical studies with ACTEMRA.

Avoid use of live vaccines concurrently with ACTEMRA as clinical safety has not been established.

ACTEMRA for subcutaneous injection is not intended for intravenous drip infusion.

Events of gastrointestinal perforation have been reported in clinical trials, primarily as complications of diverticulitis in patients treated with ACTEMRA. Use ACTEMRA with caution in patients who may be at increased risk for gastrointestinal perforation.

Treatment with ACTEMRA was associated with a higher incidence of neutropenia. Infections have been uncommonly reported in association with treatment-related neutropenia in long-term extension studies and postmarketing clinical experience.

It is not recommended to initiate ACTEMRA treatment in patients with a low neutrophil count, i.e., absolute neutrophil count (ANC) less than 2000 per mm³. In patients who develop an absolute neutrophil count less than 500 per mm³ treatment is not recommended.

Treatment with ACTEMRA was associated with a reduction in platelet counts.

It is not recommended to initiate ACTEMRA treatment in patients with a platelet count below 100,000 per mm³. In patients who develop a platelet count less than 50,000 per mm³ treatment is not recommended.

Treatment with ACTEMRA was associated with a higher incidence of transaminase elevations.

It is not recommended to initiate ACTEMRA treatment in patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN treatment is not recommended.

Treatment with ACTEMRA was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterol, and/or HDL cholesterol.

ACTEMRA is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

In the postmarketing setting, events of hypersensitivity reactions, including anaphylaxis and death have occurred in patients treated with a range of doses of intravenous ACTEMRA, with or without concomitant therapies.

Prescribers should exercise caution in considering the use of ACTEMRA in patients with preexisting or recent onset demyelinating disorders.

Treatment with ACTEMRA is not recommended in patients with active hepatic disease or hepatic impairment.

Serious cases of hepatic injury have been observed in patients taking intravenous or subcutaneous ACTEMRA. Some of these cases have resulted in liver transplant or death. Time to onset for cases ranged from months to years after treatment initiation with tocilizumab.

ACTEMRA has not been studied in combination with biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators because of the possibility of increased immunosuppression and increased risk of infection. Avoid using ACTEMRA with biological DMARDs.

Selection of a particular dose of simvastatin in RA patients should take into account the potentially lower exposures that may result after initiation of ACTEMRA (due to normalization of CYP3A4) or higher exposures after discontinuation of ACTEMRA.

In RA patients receiving 10 mg omeprazole, exposure to omeprazole was approximately 2 fold higher than that observed in healthy subjects.

Exercise caution when co-administering ACTEMRA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy.

Monoclonal antibodies, such as tocilizumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. Based on the animal data, there may be a potential risk to the fetus.

Maternal immunoglobulin G (IgG) is present in human milk.

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• Systemic lupus erythematosus, systemic sclerosis, polymyositis, large-vessel vasculitis, relapsing polychondritis, acquired hemophilia A, autoimmune hemolytic anemia, adult-onset still’s disease, crohn’s disease, behcet’s disease with posterior uveitis, polymyalgia rheumatica, remitting seronegative, symmetrical synovitis with pitting edema, spondyloarthritides, graft-versus-host disease, TNF-receptor-associated periodic syndrome, pulmonary arterial hypertension and castleman’s disease. GoToSource

• Adjuvant therapy for hemophagocytic lymphohistiocytosis. GoToSource

• Dermatomyositis. GoToSource

• New-onset type I diabetes. GoToSource

• Sjögren’s syndrome. GoToSource

• Osteoarthritis. GoToSource

• Hepatocellular carcinoma. GoToSource

• Type II diabetes, obesity, grave’s ophthalmopathy, schizophrenia, non-infectious posterior, intermediate or panuveitis, fibrous dysplasia of bone, cogan’s syndrome with iritis and aortitis. GoToSource

• Neuromyelitis optica. GoToSource 

• TAFRO syndrome. GoToSource

• Psoriatic arthritis. GoToSource

• Use in patients under 2 years of age. GoToSource

Cytopenias (neutropenia and thrombocytopenia) (low white blood cell count and low platelet count). GoToSource

Hypersensitivity reactions including anaphylaxis (life-threatening allergic reaction). GoToSource

Infusion reactions, hyperlipidaemia (high concentration of fats or lipids in the blood), transaminasemia (elevated levels of certain liver enzymes), ophthalmic herpes zoster virus infection (shingles involving the eye), allergic bronchopulmonary aspergillosis (allergic reaction to aspergillus fungus), cytomegalovirus-associated pneumonitis (infection of the lungs) and increase in miscarriage and embryo–fetal death. GoToSource

Infections (including herpes and fungal infections), strokes, malignancies (nonmelanoma skin cancer, basal cell carcinoma, lung cancer, prostate cancer, hematologic/lymphatic cancers), cellulitis (bacterial skin infection), urinary tract infection, sepsis (life-threatening response to infection), pulmonary embolism (blockage in one of the pulmonary arteries in lungs) and tendon rupture. GoToSource

Cardiorespiratory arrest and gastrointestinal hemorrhage. GoToSource

Pyelonephritis (severe kidney infection), acute bronchitis, bladder cancer, breast cancer, large intestine carcinoma and intraductal papilloma (benign tumor in the breast). GoToSource

Fulminant bilateral papilloedema (optic disc swelling) and vision loss. GoToSource

Acute pancreatitis (inflammation of the pancreas). GoToSource

Septic arthritis (joint inflammation caused by infection). GoToSource

Aggravation of multiple sclerosis. GoToSource

Multiple halo naevi (mole with a white ring around it). GoToSource

Psoriasiform rash (rash that resembles psoriasis). GoToSource

Multifocal encephalopathy and limbic encephalitis (inflammation of the brain). GoToSource

Secondary sialadenitis (inflammation of salivary gland) in rheumatoid arthritis patients. GoToSource

Mouth ulcers. GoToSource

Staphylococcus aureus infection. GoToSource

Pulmonary nontuberculous mycobacteriosis (lung infection). GoToSource

Multiple ulcers in the small and large intestines. GoToSource

Exacerbation of interstitial lung disease. GoToSource

Peripheral neuropathy (nerve damage) and skin ulcers. GoToSource

Pneumonia, myocardial infarction, increased lipid and liver function parameters, gastrointestinal perforation and reactivation of tuberculosis. GoToSource

Lawsuits filed for heart failure, stroke, pancreatitis, lung disease and gastrointestinal perforations.