Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis

Serious Infections

• Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)]. 
•  Reported infections include:
      Active tuberculosis, which may present with pulmonary or extrapulmonary disease. 
      Invasive fungal infections, including candidiasis and pneumocystosis. 
      Bacterial, viral, and other infections due to opportunistic pathogens.
• Avoid use of OPZELURA in patients with an active, serious infection, including localized infectns. If a serious infection develops, interrupt OPZELURA until the infection is controlled.
• The risks and benefits of treatment with OPZELURA 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 OPZELURA [see Warnings and Precautions (5.1)].

Mortality

• In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor.

Malignancy and Lymphoproliferative Disorders

• Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Major Adverse Cardiovascular Events (MACE)

• In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke.

Thrombosis

• Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately.