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PRESCRIBING INFORMATION (PI)

RINVOQ® (upadacitinib) 15mg prolonged-release tablets; 30mg prolonged-release tablets and 45mg prolonged-release tablets

Refer to Summary of Product Characteristics (SmPC) before prescribing.

PRESENTATIONS: Each prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 15mg upadacitinib in the 15mg tablet, 30mg in 30mg tablet and 45mg in 45mg tablet.

INDICATIONS: For the 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) or moderately to severely active Crohn’s disease (CD) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

DOSAGE AND ADMINISTRATION: Treatment should be initiated and supervised by physicians experienced in the diagnosis and treatment of RA, PsA, AS, nr-axSpA, AD, UC or CD. Posology: (oral administration, with or without food, any time of day, to be swallowed whole. Food or drink containing grapefruit should be avoided during treatment); RA, PsA, AS and nr-axSpA: 15mg once daily. 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 AS and nr-axSpA 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. 15mg once daily is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy. Patients ≥65 years of age, and adolescents 12-17 years weighing at least 30kg; the recommended dose is 15mg once daily. 30mg once daily is not recommended for patients with AD receiving chronic treatment with strong CYP3A4 inhibitors. The lowest effective dose to maintain response should be used. Consideration should be given to discontinuing treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. UC: Induction; 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; 15mg or 30mg once daily based on individual patient presentation. The lowest effective dose to maintain response should be used. Dose of 15mg is recommended for patients at higher risk of VTE, MACE and malignancy. Patients ≥65 years of age, the recommended dose is 15mg once daily. A dose of 30mg once daily may be appropriate for some patients, such as those with high disease burden or requiring 16 week induction treatment who are not at higher risk of VTE, MACE and malignancy or who do not show adequate therapeutic benefit to 15mg once daily. Patients receiving strong inhibitors CYP3A4 the recommended induction dose is 30mg once daily and maintenance dose is 15mg once daily. CD: Induction; 45mg once daily for 12 weeks. For patients who have not achieved adequate therapeutic benefit after the initial 12 week induction, 30mg once daily may be appropriate. For these patients, upadacitinib should be discontinued if there is no evidence of therapeutic benefit after 24 weeks of treatment. Maintenance; 15mg or 30mg once daily based on individual patient presentation. The lowest effective dose to maintain response should be used. 15mg once daily is recommended for patients at higher risk of VTE, MACE and malignancy. 30mg once daily may be appropriate for patients with high disease burden who are not at higher risk of VTE, MACE and malignancy, or who do not show adequate therapeutic benefit to 15mg once daily. Patients ≥65 years of age, the recommended dose is 15mg once daily. Patients receiving strong inhibitors of CYP3A4 the recommended induction dose is 30mg once daily and maintenance dose is 15mg once daily. Special Populations: Elderly: RA, PsA, AS and nr-axSpA: there are limited data for patients ≥75 years of age. AD: doses higher than 15mg in patients >65 years are not recommended. UC and CD maintenance: doses higher than 15mg once daily are not recommended in patients >65 years. In 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 dose adjustments. Upadacitinib is not recommended in patients with end stage renal disease. Hepatic impairment: No dose adjustment required in mild or moderate hepatic impairment. Upadacitinib should not be used in patients with severe hepatic impairment. Paediatric Population: Safety and efficacy in RA, AS, PsA, nr-axSpA, UC, and CD in children and adolescents aged 0 to <18 years and in AD in children under 12 years has not been established. No data are available. No clinical exposure data are available in AD adolescents < 40kg.

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

SPECIAL WARNINGS AND PRECAUTIONS: Refer to SmPC for full details.

Upadacitinib should only be used if no suitable treatment alternatives are available in patients: 65 years of age and older; with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers) or with malignancy risk factors (e.g. current malignancy or history of malignancy).

Immunosuppression: Combination with potent immunosuppressants, biologic DMARDs or other Janus kinase (JAK) inhibitors has not been evaluated and is not recommended. Serious infections: Serious and fatal infections have been reported. Most frequent reported include pneumonia and cellulitis. Bacterial meningitis, sepsis and opportunistic infections including tuberculosis, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis have been reported. 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; who have been exposed to tuberculosis (TB); with a history of a serious or an opportunistic infection; who have resided or travelled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with upadacitinib. Upadacitinib therapy should be interrupted if a patient develops a serious or opportunistic infection. A patient who develops a new infection during treatment with upadacitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and upadacitinib therapy should be interrupted if the patient is not responding to antimicrobial therapy. Upadacitinib therapy may be resumed once the infection is controlled and only following careful consideration of benefit-risk. Higher rate of serious infections with upadacitinib 30mg compared to upadacitinib 15mg. Higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used with the elderly and diabetic patients given the higher risk to these patients in general. In patients aged >65 years, upadacitinib should only be used if no suitable treatment alternatives are available. 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 or in patients with risk factors for TB infection and consult with a physician with experience in TB therapy. 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: Viral reactivation, including cases of herpes virus reactivation (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 JAK inhibitors, including upadacitinib. Higher rate of malignancies observed with upadacitinib 30mg compared to upadacitinib 15mg. In patients aged > 65 years, patients 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. Non-melanoma skin cancer (NMSC): Higher rate of NMSC have been reported with upadacitinib 30mg compared to upadacitinib 15mg. Periodic skin examination recommended for all patients, particularly those with risk factors for skin cancer. Haematological abnormalities: If Absolute Neutrophil Count <1 x 109 cells/L, Absolute Lymphocyte Count <0.5 x 109 cells/L or Hb <8 g/dL do not start treatment or temporarily interrupt existing therapy. Evaluate these haematological parameters at baseline and then no later than 12 weeks after initiation of treatment. Thereafter evaluate according to individual patient management. Gastrointestinal perforations: Events of diverticulitis and gastrointestinal perforations have been reported. Use with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking non-steroidal anti- inflammatory drugs (NSAIDs), corticosteroids, or opioids). Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. Major adverse cardiovascular events: MACE have been reported. In patients aged > 65 years, 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: Treatment with upadacitinib was associated with dose-dependent increases in lipid parameters, including total cholesterol, LDL and HDL. Monitor lipids total at 12 weeks and thereafter according to international guidelines. 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. In patients with cardiovascular or malignancy risk factors, upadacitinib should only be used if no suitable treatment alternatives are available. In patients with known VTE risk factors other than cardiovascular or malignancy risk factors, upadacitinib should be used with caution. VTE risk factors other than cardiovascular or malignancy risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder. Patients should be re-evaluated periodically during upadacitinib treatment to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue upadacitinib in patients with suspected VTE, regardless of dose. Hypersensitivity reactions: Serious hypersensitivity reactions (e.g. anaphylaxis and angioedema) have been reported. If a clinically significant hypersensitivity reaction occurs discontinue therapy and manage appropriately. Hypoglycaemia in patients treated for diabetes: Hypoglycaemia has been reported in patients receiving medication for diabetes. Dose adjustment of anti-diabetic medication may be necessary if hypoglycaemia occurs.

INTERACTIONS: Avoid food or drink containing grapefruit. Caution should be used with strong CYP3A4 inhibitors, see SmPC for dosing considerations. Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors. Alternatives to strong CYP3A4 inhibitors should be considered when used in the long term. CYP3A4 inducers may reduce therapeutic effect. Patients should be monitored for changes in disease activity if upadacitinib is co-administered with strong CYP3A4 inducers.

FERTILITY, PREGNANCY AND LACTATION: Women of childbearing potential: should be advised to use effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. For indication(s) licensed in adolescents, female adolescent patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib. Pregnancy: Upadacitinib is contraindicated during pregnancy. There are no or limited data on the use of upadacitinib in pregnant women. Studies in animals have shown reproductive toxicity. If a patient becomes pregnant while taking upadacitinib the parents should be informed of the potential risk to the foetus. Breast-feeding: Upadacitinib should not be used during breast-feeding. A decision must be made whether to discontinue breast-feeding or to discontinue upadacitinib therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility: The effect of upadacitinib on human fertility has not been evaluated. Animal studies do not indicate effects with respect to fertility.

ABILITY TO DRIVE AND USE MACHINES: Upadacitinib may have a minor influence on the ability to drive and use machines because dizziness and vertigo may occur during treatment.

UNDESIRABLE EFFECTS: See SmPC for full list of adverse events.

Very common (≥1/10): Upper respiratory tract infections and acne.

Common (≥1/100 to <1/10) including serious: Bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, urinary tract infection, pneumonia, non-melanoma skin cancer (basal cell and squamous cell carcinoma of skin), anaemia, neutropaenia, lymphopaenia, hypercholesterolaemia, hyperlipidaemia, headache, dizziness, vertigo, cough, abdominal pain, nausea, urticaria, rash, fatigue, pyrexia, increased blood CPK/ALT/AST and increased weight.

Serious also include: Serious infections including sepsis, cellulitis, bacterial meningitis, opportunistic infections including TB and cryptococcosis; lymphoma, malignancies, MACE, VTE including DVT & PE, serious hypersensitivity reactions including anaphylactic reaction and angioedema, gastrointestinal perforation.

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

LEGAL CLASSIFICATION: POM

MA HOLDER: further information available from AbbVie Ltd, Maidenhead, SL6 4UB, UK

DATE OF REVISION: May 2024

DOCUMENT NUMBER: JAKa-UK-00030-C/PI-RINVOQ-18

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk or via the MHRA Yellow Card app, available in the Google Play or Apple App Stores. Adverse events should also be reported to AbbVie on [email protected]

 

 

UK-UPAD-240029. Date of preparation: June 2024