PRESCRIBING INFORMATION (PI)

RINVOQ^▼(upadacitinib) 15 mg prolonged-release tablets; 30 mg prolonged-release tablets; 45 mg prolonged-release tablets.

Refer to Summary of Product Characteristics (SmPC) for full prescribing information.

PRESENTATION: Each tablet contains upadacitinib hemihydrate, equivalent to 15 mg upadacitinib in the 15 mg tablet, 30 mg in 30 mg tablet, 45 mg in 45 mg tablet.

INDICATION: Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment of active ankylosing spondylitis (AS, radiographic axial spondyloarthritis) in adult patients who have responded inadequately to conventional therapy. Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. Treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or biologic agent.

DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of RA, PsA, AS, nr-axSpA, AD or UC. Dosage: The recommended dose is 15mg once daily for RA, PsA, AS and nr-axSpA. Consideration should be given to discontinuing treatment in patients with AS and nr-axSpA who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. AD: 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). The lowest effective dose to maintain response should be used. Dose of 15 mg is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy. Patients ≥ 65 years of age, the recommended dose is 15 mg once daily. Adolescents 12-17 years weighing at least 30 kg; 15mg once daily. Consideration should be given to discontinuing treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. UC: Induction; The recommended dose is 45mg once daily for 8 weeks. For patients who do not achieve therapeutic benefit by week 8, 45mg once daily may be continued for an additional 8 weeks. Patients who show no evidence of therapeutic benefit by week 16 should discontinue treatment. Maintenance; the recommended dose is 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). The lowest effective dose to maintain response should be used. Dose of 15 mg is recommended for patients at higher risk of VTE, MACE and malignancy. Patients ≥ 65 years of age, the recommended dose is 15 mg once daily. In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care. Patients receiving strong inhibitors of cytochrome P450 (CYP) 3A4 the recommended induction dose is 30 mg once daily and maintenance dose is 15 mg once daily (see SmPC for more details). Avoid food/drink containing grapefruit. Special Populations: Elderly: For AD patients ≥ 65 years of age a dose higher than 15mg is not recommended. For RA, PsA, AS and nr-axSpA there are limited data for patients ≥ 75 years of age. For UC maintenance therapy, a dose higher than 15 mg once daily is not recommended in patients ≥ 65 years of age. For UC patients ≥ 75 of age the safety and efficacy of upadacitinib has not been established. Renal: No dose adjustment required in mild-moderate renal impairment.  Patients with severe renal impairment should use upadacitinib with caution (See SmPC for full details). Upadacitinib has not been studied in subjects with end stage renal disease and is therefore not recommended for use. Hepatic impairment: Should not be used in patients with severe Child Pugh C impairment. Paediatric Population: Safety and efficacy in RA, AS, PsA, nr-axSpA and UC in children and adolescents aged 0 to < 18 years and in AD in children under 12 has not been established. No clinical exposure data are available in AD adolescents < 40 kg.

CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active TB or active serious infections. Severe hepatic impairment. Pregnancy.

SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details.

Patients ≥65 years of age: Only use upadacitinib if no suitable treatment alternatives are available. Increased risk of adverse reactions with upadacitinib 30mg once daily. Recommended dose for long-term use is 15mg once daily. Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, 6-mercaptopurine, ciclosporin, tacrolimus, and biologic DMARDs or other Janus kinase (JAK) inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded. Serious infections: Serious and fatal infections have been reported. Frequently reported pneumonia and cellulitis. Bacterial meningitis and sepsis have been reported. Opportunistic infections reported – tuberculosis, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active, serious infection including localised infections. Consider the risk/benefit of treatment in patients with; chronic or recurrent infection, history of serious or opportunistic infection, those exposed to tuberculosis (TB), those who have resided or travelled in areas of endemic TB or endemic mycoses or with underlying conditions that may predispose them to infection. Closely monitor patients and interrupt treatment if there are signs and symptoms of infection pre and post treatment. If infection is controlled, resume treatment following risk/benefit consideration. Higher rate of serious infections with upadacitinib 30 mg compared to upadacitinib 15 mg. Use with caution when treating patients ≥65 years of age and patients with diabetes. Tuberculosis: Pre-screen patients for active or latent TB. Upadacitinib should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB and consult with a physician with experience in TB therapy and whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy. Viral reactivation: Cases of herpes virus reactivation have been reported e.g., herpes zoster. If herpes zoster is reactivated, consider interruption of therapy until the episode resolves. Screen pre-therapy for viral hepatitis and monitor regularly for reactivation. Patients positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis B is detected while receiving therapy, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines. Malignancy: Lymphoma and other malignancies have been reported in patients receiving upadacitinib. Higher rate observed with upadacitinib 30 mg compared to upadacitinib 15 mg. In patients ≥65 years or who are current or past long-time smokers, or with other malignancy risk factors (e.g., current malignancy or history of malignancy) upadacitinib should only be used if no suitable treatment alternatives are available. (see SmPC). Non-melanoma skin cancer: Higher rate observed with upadacitinib 30 mg compared to upadacitinib 15 mg. Periodic skin examination recommended for all patients, particularly those with risk factors for skin cancer. Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1,000 cells/mm³, Absolute Lymphocyte Count <500 cells/mm³ or Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Diverticulitis: Diverticulitis may cause gastrointestinal perforation. Use with caution in patients with diverticular disease and especially when chronically treated with concomitant medications associated with an increased risk of diverticulitis: NSAIDs, corticosteroids and opioids. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification to prevent gastrointestinal perforation. Major adverse cardiovascular events: MACE have been reported in patients receiving upadacitinib. In patients ≥65 years or who are current or past long-time smokers, or patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, upadacitinib should only be used if no suitable treatment alternatives are available. Lipids: Upadacitinib was associated with dose-dependent increases in lipid parameters, including total cholesterol, LDL and HDL (see SmPC). Monitor lipids at 12 weeks and thereafter according to international guidelines. Elevated LDL in clinical trials decreased to pre-treatment levels in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded. Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for upadacitinib. Use therapy with caution in patients with VTE risk factors other than cardiovascular or malignancy risk factors. Risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder. Re-evaluate patients periodically to assess for changes in VTE risk. If clinical features of VTE occur discontinue therapy and evaluate promptly. Hypersensitivity reactions: Serious hypersensitivity reactions (e.g. anaphylaxis and angioedema) have been reported. If clinically significant hypersensitivity reaction occurs discontinue therapy and manage appropriately. Pregnancy and Lactation: Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of Upadacitinib. Upadacitinib should not be used during breast-feeding.

ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions.

Very common adverse reactions (≥1/10): Upper respiratory tract infections and acne. Common adverse reactions (≥1/100 to <1/10): Bronchitis, Herpes zoster, Herpes simplex, folliculitis, influenza, urinary tract infection, pneumonia, non-melanoma skin cancer, anaemia, neutropaenia, lymphopaenia, hypercholesterolaemia, hyperlipidaemia, cough, abdominal pain, nausea, urticaria, rash, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache. Serious adverse reactions: The most common serious adverse reactions were serious infections. Please see section on serious infections above.

LEGAL CLASSIFICATION: POM

FURTHER INFORMATION: available from AbbVie Ltd, Maidenhead, SL6 4UB, UK

MARKETING AUTHORISATION NUMBERS/ PRESENTATIONS/NHS LIST PRICE: Great Britain (GB) PLGB 41042/0042, Northern Ireland (NI) EU/1/19/1404/001: RINVOQ 15 mg prolonged-release tablets in cartons of 28 tablets: £805.56. GB PLGB 41042/0044, NI EU/1/19/1404/006 RINVOQ 30 mg prolonged-release tablets in cartons of 28 tablets: £1281.54. GB PLGB 41042/0087, NI EU/1/19/1404/010: RINVOQ 45 mg prolonged-release tablets in cartons of 28 tablets £2087.10

DATE OF REVISION: February 2023

PI-RINVOQ-013

UK-UPAD-220323. Date of preparation: March 2023