Tocilizumab (1 brand name, 1 dosage form, 2 routes)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION, INTRAVENOUS, SUBCUTANEOUS.
Brand Names
- ACTEMRA
Boxed Warning
Patients treated with tocilizumab products including AVTOZMA are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt AVTOZMA until the infection is controlled. Reported infections include: Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients, except those with COVID-19, should be tested for latent tuberculosis before AVTOZMA use and during therapy. Treatment for latent infection should be initiated prior to AVTOZMA 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 AVTOZMA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVTOZMA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1)].
Contraindications
AVTOZMA is contraindicated in patients with known hypersensitivity to tocilizumab products [see Warnings and Precautions (5.6)].
Adverse Reactions
The following serious adverse reactions are described elsewhere in labeling: Serious Infections [see Warnings and Precautions (5.1)] Gastrointestinal Perforations [see Warnings and Precautions (5.2)] Laboratory Parameters [see Warnings and Precautions (5.4)] Immunosuppression [see Warnings and Precautions (5.5)] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.6)] Demyelinating Disorders [see Warnings and Precautions (5.7)] Active Hepatic Disease and Hepatic Impairment [see Warnings and Precautions (5.8)] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.
Mechanism of Action
Tocilizumab products bind to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and have been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.
Overdosage
There are limited data available on overdoses with tocilizumab products. One case of accidental overdose was reported with intravenous tocilizumab in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.