Tocilizumab

Tocilizumab is associated with transaminase elevations. Monitor transaminases. Treatment should be discontinued in patients who develop elevated ALT or AST >5 x ULN. Patients receiving concomitant hepatotoxic drugs (eg, methotrexate) are at an increased risk of developing elevated transaminases; elevations are typically reversible and do not result in clinically evident hepatic injury.

Use with caution in patients at increased risk for GI perforation; perforation has been reported, typically secondary to diverticulitis. Monitor for new-onset abdominal symptoms; promptly evaluate if new symptoms occur.

Neutropenia and thrombocytopenia may occur; may require treatment interruption, dose or interval modification, or discontinuation. Monitor neutrophils and platelets. Do not initiate treatment in patients with giant cell arteritis, polyarticular juvenile idiopathic arthritis, rheumatoid arthritis, or systemic juvenile idiopathic arthritis with an ANC 3 or platelet count 3; discontinue treatment for ANC 3 or platelet count 3.

Herpes zoster reactivation has been reported.

Therapy is associated with increases in total cholesterol, triglycerides, LDL, and/or HDL; monitor ~4 to 8 weeks after initiation, then approximately every 6 months. Hyperlipidemia should be managed according to current guidelines.

May cause hypersensitivity or anaphylaxis; anaphylactic events including fatalities have been reported with IV administration; hypersensitivity reactions have occurred in patients who were premedicated, in patients with and without a prior history of hypersensitivity, and as early as the first infusion. Medications for the treatment of hypersensitivity reactions should be available for immediate use. Patients should seek medical attention if symptoms of hypersensitivity reaction occur with SubQ use. Stop immediately and permanently discontinue treatment in patients who develop a hypersensitivity reaction to tocilizumab. In clinical studies, reactions requiring treatment discontinuation included generalized erythema, rash, and urticaria.

Serious and potentially fatal infections (including active tuberculosis, invasive fungal, bacterial, viral, protozoal, and other opportunistic infections) have been reported in patients receiving tocilizumab; infection may lead to hospitalization or death. Most of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Patients should be closely monitored for signs and symptoms of infection during and after treatment. If serious infection occurs during treatment, withhold tocilizumab until infection is controlled. Prior to treatment initiation, carefully consider risk versus benefit in patients with chronic or recurrent infections, tuberculosis exposure, history of or current opportunistic infection, underlying conditions predisposing to infection, or patients residing in or with travel to areas of endemic tuberculosis or endemic mycosis. The most common serious infections occurring have included pneumonia, UTI, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis, and bacterial arthritis. Do not administer tocilizumab to a patient with an active infection, including localized infection. Interrupt treatment for serious infection, opportunistic infection, or sepsis.

Use of tocilizumab may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined; however, malignancies were observed in clinical trials.

Tuberculosis (pulmonary or extrapulmonary) has been reported in patients receiving tocilizumab; both reactivation of latent infection and new infections have been reported. Patients should be tested for latent tuberculosis infection before and during therapy; consider treatment of latent tuberculosis used prior to tocilizumab treatment. Some patients who test negative prior to therapy may develop active infection; monitor for signs and symptoms of tuberculosis during and after treatment in all patients. Patients should be evaluated for tuberculosis risk factors with a tuberculin skin test prior to starting therapy. Consider antituberculosis treatment in patients with a history of latent or active tuberculosis if adequate treatment course cannot be confirmed, and for patients with risk factors for tuberculosis despite a negative test. Disease-related concerns:

Use with caution in patients with preexisting or recent onset CNS demyelinating disorders; rare cases of CNS demyelinating disorders (multiple sclerosis and chronic inflammatory demyelinating polyneuropathy) have occurred. All patients should be monitored for signs and symptoms of demyelinating disorders.

Use is not recommended in patients with active hepatic disease or hepatic impairment. Monitor ALT and AST. Do not initiate treatment if ALT or AST is >1.5 times ULN. Concurrent drug therapy issues:

Concomitant use with other biological DMARDs (eg, TNF blockers, IL-1 receptor blockers, anti-CD20 monoclonal antibodies, selective costimulation modulators) has not been studied and should be avoided due to the increased risk of infection.

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Infection has been reported at a higher incidence in elderly patients compared with younger adults; use with caution in elderly patients. Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Other warnings/precautions:

SubQ administration is only indicated for adult patients with rheumatoid arthritis and giant cell arteritis (GCA). Do not use SubQ injection for IV infusion. Do not administer IV for the treatment of GCA.

Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of infection from live vaccines in patients receiving therapy.