• Hypersensitivity Reactions: Hypersensitivity reactions, such as angioedema, have been reported. Discontinue if a clinically significant hypersensitivity reaction occurs. • Infections: SOTYKTU may increase the risk of infection. Avoid use in patients with active or serious infection. If a serious infection develops, discontinue SOTYKTU until the infection resolves. • Tuberculosis: Evaluate for latent or active TB prior to initiating treatment with SOTYKTU. • Malignancy: Malignancies including lymphomas were observed in clinical trials with SOTYKTU. Consider the benefits and risks prior to initiating or continuing SOTYKTU in patients with a malignancy. • Rhabdomyolysis and Elevated CPK: Discontinue SOTYKTU if markedly elevated CPK levels occur or myopathy is diagnosed or suspected . • Laboratory Abnormalities: Periodically evaluate serum triglycerides. Evaluate liver enzymes at baseline and during SOTYKTU treatment in patients with known or suspected liver disease. • Immunizations: Avoid use of SOTYKTU with live vaccines. • Potential Risks Related to JAK Inhibition: It is not known whether TYK2 inhibition may be associated with the observed or potential adverse reactions of JAK inhibition. Higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with a JAK inhibitor compared to those treated with TNF blockers in patients with rheumatoid arthritis (RA). SOTYKTU is not approved for use in RA. 5.1 Hypersensitivity Reactions Hypersensitivity reactions, such as angioedema, have been reported in subjects receiving SOTYKTU. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue SOTYKTU
Infections SOTYKTU may increase the risk of infections. Serious infections have been reported in subjects who received SOTYKTU. The most common serious infections reported with SOTYKTU included pneumonia and COVID-19 . Avoid use of SOTYKTU in patients with an active or serious infection. Consider the risks and benefits of SOTYKTU prior to initiating treatment in patients: • with chronic or recurrent infection • who have been exposed to tuberculosis • with a history of a serious or an opportunistic infection • with underlying conditions that may predispose them to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SOTYKTU. Patients who develops a new infection during treatment with SOTYKTU should undergo prompt and complete diagnostic testing, have appropriate antimicrobial therapy be initiated, and be closely monitored. Interrupt SOTYKTU if a serious infection occurs. Do not resume SOTYKTU until the infection resolves or is adequately treated. Viral Reactivation Herpes virus reactivation (e.g., herpes zoster, herpes simplex) was reported in clinical trials with SOTYKTU . In the 16‑week placebo-controlled period of Trials PSO-1 and PSO-2, herpes simplex infections were reported in 17 subjects (6.8 per 100 patient‑years) treated with SOTYKTU, and 1 subject (0.8 per 100 patient-years) treated with placebo. Multidermatomal herpes zoster was reported in an immunocompetent subject who received SOTYKTU. The clinical implications of SOTYKTU on viral hepatitis reactivation are unknown. Subjects with positive screening tests for hepatitis B or C, or chronic hepatitis B, or untreated hepatitis C were excluded from clinical trials or closely monitored for evidence of reactivation. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with SOTYKTU. If signs of reactivation occur, consult a hepatitis specialist. SOTYKTU is not recommended for use in patients with active hepatitis B or hepatitis C
Tuberculosis In Trials PSO-1 and PSO-2, of 4 subjects with latent tuberculosis (TB) who were treated with SOTYKTU and received appropriate TB prophylaxis, no subjects developed active TB (during the mean follow-up of 34 weeks). One subject, who did not have latent TB, developed active TB after receiving 54 weeks of SOTYKTU. Evaluate patients for latent and active TB infection prior to initiating treatment with SOTYKTU. Do not administer SOTYKTU to patients with active TB. Initiate treatment of latent TB prior to administering SOTYKTU. Consider anti-TB therapy prior to initiation of SOTYKTU in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients receiving SOTYKTU for signs and symptoms of active TB during treatment
Malignancy including Lymphomas Malignancies, including lymphomas, were observed in clinical trials with SOTYKTU . Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with SOTYKTU, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer) and patients who develop a malignancy during treatment with SOTYKTU
Rhabdomyolysis and Elevated CPK Cases of rhabdomyolysis were reported in subjects treated with SOTYKTU resulting in interruption or discontinuation of SOTYKTU dosing. Treatment with SOTYKTU was associated with an increased incidence of asymptomatic creatine phosphokinase (CPK) elevation and rhabdomyolysis compared to treatment with placebo. Discontinue SOTYKTU if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever
Laboratory Abnormalities Triglyceride Elevations - Treatment with SOTYKTU was associated with increases in triglyceride levels . The effect of this elevated parameter on cardiovascular morbidity and mortality has not been determined. Periodically evaluate serum triglycerides according to the clinical guidelines for hyperlipidemia while patients are receiving treatment with SOTYKTU. Manage patients according to clinical guidelines for the management of hyperlipidemia. Liver Enzyme Elevations - Treatment with SOTYKTU has been associated with liver enzyme elevation. Liver serum transaminase elevations ≥3 times the ULN have been reported in subjects treated with SOTYKTU . Evaluate liver enzymes at baseline and during treatment SOTYKTU in patients with known or suspected liver disease according to routine patient management. If increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt SOTYKTU until a diagnosis of liver injury is excluded
Immunizations Prior to initiating therapy with SOTYKTU, complete all age-appropriate immunizations according to current immunization guidelines including prophylactic herpes zoster vaccination. Avoid use of live vaccines in patients treated with SOTYKTU. The response to live or non-live vaccines has not been evaluated
Potential Risks Related to JAK Inhibition It is not known whether TYK2 inhibition may be associated with the observed or potential adverse reactions of Janus Kinase (JAK) inhibition. In a large, randomized, postmarketing safety trial of a JAK inhibitor in rheumatoid arthritis (RA), patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. SOTYKTU is not approved for use in RA.
