CELLTRION
CONNECT® A patient support program that provides personalized support to you and your patients prescribed AVTOZMA®

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS

Patients treated with tocilizumab products including AVTOZMA 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 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.

Contraindications: Known hypersensitivity to tocilizumab products.

Serious Infections. Serious and sometimes fatal infections, including bacterial, mycobacterial, invasive fungal, viral, and opportunistic infections, have been reported with tocilizumab products, including AVTOZMA. Common serious infections include pneumonia, urinary tract infections, cellulitis, herpes zoster, and sepsis, while opportunistic infections such as tuberculosis and cryptococcus have also occurred. Patients with chronic or recurrent infections, tuberculosis exposure, or underlying conditions predisposing to infections should have the risks and benefits of AVTOZMA carefully evaluated. Monitor patients closely during and after treatment for signs of infection, and discontinue AVTOZMA if a serious infection develops, initiating appropriate antimicrobial therapy as needed.

Gastrointestinal (GI) Perforation. Gastrointestinal perforation events, primarily associated with diverticulitis, have been reported in clinical trials of tocilizumab. Use AVTOZMA cautiously in patients at increased risk for gastrointestinal perforation. Promptly evaluate any patient experiencing new abdominal symptoms to ensure early detection and management of this condition.

Hepatotoxicity. Serious hepatic injury, including cases of liver transplant and death, has occurred with tocilizumab products, with onset ranging from months to years. Some cases involved marked transaminase elevations (>5x ULN), while others presented with mild elevations and symptoms of liver dysfunction. Risk is higher with hepatotoxic drugs like methotrexate. Baseline and regular liver tests are required for RA, GCA, PJIA, and SJIA patients, with specific monitoring intervals based on the condition. Do not initiate AVTOZMA if ALT or AST >1.5x ULN (RA/GCA) or >10x ULN (COVID-19), and discontinue if ALT or AST >5x ULN. Evaluate symptoms of liver injury promptly, and only restart treatment if liver test abnormalities are resolved and attributed to another cause.

Changes in Laboratory Parameters. Treatment with tocilizumab products, including AVTOZMA, has been associated with neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities. Infections are uncommon with treatment-related neutropenia, but AVTOZMA should not be initiated in RA or GCA patients with ANC <2000/mm³ or platelet counts <100,000/mm³, and treatment is not recommended if ANC drops below 500/mm3 or platelets below 50,000/mm³. For COVID-19 patients, AVTOZMA is not recommended with ANC <1000/mm³ or platelets <50,000/mm³. Monitor neutrophils, platelets, and liver enzymes 4–8 weeks after starting therapy and every 3 months thereafter, adjusting treatment as needed. Lipid levels, including cholesterol and triglycerides, may increase and should be assessed 4–8 weeks after initiation, with management per clinical guidelines. A similar pattern is observed in PJIA and SJIA, requiring specific monitoring intervals for these populations. Refer to Dosage and Administration for modifications based on test results.

Immunosuppression. The effect of tocilizumab products on malignancy development is unknown, though malignancies were observed in clinical studies. As an immunosuppressant, AVTOZMA may increase the risk of malignancies.

Hypersensitivity Reactions, Including Anaphylaxis. Hypersensitivity reactions, including anaphylaxis and fatal events, have been reported with tocilizumab products. Anaphylaxis requiring discontinuation occurred in 0.1% to 0.7% of trial patients, with postmarketing cases reported at various doses, with or without premedication, and as early as the first infusion. AVTOZMA intravenous infusions must be administered by healthcare professionals equipped to manage anaphylaxis. For subcutaneous use, patients must seek immediate medical attention if hypersensitivity symptoms occur. Discontinue AVTOZMA permanently if anaphylaxis or other hypersensitivity reaction occurs. Do not use in patients with known hypersensitivity to tocilizumab products.

Demyelinating Disorders. The impact of tocilizumab on demyelinating disorders is unknown, but rare cases like multiple sclerosis and polyneuropathy were reported in RA studies. Monitor for symptoms and use caution in patients with preexisting or recent demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment. Treatment with AVTOZMA is not recommended.

Live Vaccines. Avoid concurrent use of live vaccines with AVTOZMA, as clinical safety and secondary transmission risk are unknown. Follow guidelines on timing between live vaccines and AVTOZMA.

Adverse Reactions reported in ≥5% of tocilizumab-treated patients include upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, and injection site reactions.