Upadacitinib

Source: UK SPC (eMC) §4.2 for RINVOQ 15 mg prolonged-release tablets (https://www.medicines.org.uk/emc/product/10972/smpc). VERBATIM: 'Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis — The recommended dose of upadacitinib is 15 mg once daily.' In axial spondyloarthritis, consider discontinuing treatment in patients who have shown no clinical response after 16 weeks (some patients with an initial partial response may improve with continued treatment beyond 16 weeks). INITIATION: treatment should be initiated and supervised by physicians experienced in the diagnosis and treatment of the indicated conditions. TREATMENT MUST NOT BE INITIATED if the absolute lymphocyte count is < 0.5 x 10^9 cells/L, the absolute neutrophil count is < 1 x 10^9 cells/L, or haemoglobin is < 8 g/dL. DOSE INTERRUPTION: interrupt if a serious infection develops until the infection is controlled; interrupt if ANC < 1 x 10^9 cells/L, ALC < 0.5 x 10^9 cells/L or Hb < 8 g/dL (restart once values return above these thresholds); interrupt temporarily if drug-induced liver injury is suspected. MONITORING: evaluate ANC/ALC/Hb at baseline and no later than 12 weeks after initiation, then per individual patient management; evaluate hepatic transaminases at baseline then per routine management; evaluate lipids 12 weeks after initiation and manage per international hyperlipidaemia guidelines. OTHER INDICATIONS IN THE SAME SPC — giant cell arteritis: 15 mg once daily in combination with a tapering course of corticosteroids (monotherapy should not be used for acute relapses; 15 mg once daily can be continued as monotherapy after corticosteroids are stopped). Atopic dermatitis: 15 mg or 30 mg once daily based on individual patient presentation — 15 mg for patients at higher risk of VTE, MACE and malignancy; 30 mg may be appropriate for high disease burden in patients not at higher risk or with inadequate response to 15 mg; use the lowest effective dose; consider discontinuing if no evidence of therapeutic benefit after 12 weeks. Ulcerative colitis: induction 45 mg once daily for 8 weeks (may continue a further 8 weeks if inadequate benefit at week 8; discontinue if no benefit by week 16), then maintenance 15 mg or 30 mg once daily. Crohn's disease: induction 45 mg once daily for 12 weeks, then maintenance 15 mg or 30 mg once daily (discontinue if no benefit after 24 weeks in those needing 30 mg after inadequate induction response). ELDERLY: limited data in patients 75 years and older (safety and efficacy not established); for atopic dermatitis, doses higher than 15 mg once daily are not recommended at 65 years and older; for ulcerative colitis and Crohn's disease, maintenance doses higher than 15 mg once daily are not recommended at 65 years and older. HEPATIC IMPAIRMENT: no dose adjustment in mild (Child-Pugh A) or moderate (Child-Pugh B); must not be used in severe (Child-Pugh C) — this is a contraindication. PAEDIATRIC (fixed dose, NOT per-kg, so paedDose is null): for atopic dermatitis in adolescents 12 to 17 years of age weighing at least 30 kg, 15 mg once daily is recommended, increased to 30 mg once daily if response to 15 mg is inadequate. Safety and efficacy have not been established in children with atopic dermatitis below 12 years, nor in children and adolescents aged 0 to less than 18 years with rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, ulcerative colitis or Crohn's disease; there is no relevant paediatric use in giant cell arteritis. Female paediatric patients and/or their parents/caregivers should be told to contact the treating physician once the patient experiences menarche while taking upadacitinib. Verify any under-18 use against a children's formulary. §4.5 was not retrieved from the UK SPC in this bundle — the CYP3A4 entries below come from the §4.2 interactions paragraph and the US RINVOQ label §7.