Uparen

• Approved Indications:
• Moderate to severe rheumatoid arthritis (RA) in adults with inadequate response or intolerance to methotrexate or other conventional synthetic DMARDs.
• Active psoriatic arthritis (PsA) in adults with inadequate response or intolerance to one or more DMARDs.
• Moderate to severe atopic dermatitis in adults and adolescents aged 12 years and older who are candidates for systemic therapy.
• Active ankylosing spondylitis (AS) in adults with inadequate response to conventional therapy.
• Active non-radiographic axial spondyloarthritis in adults with objective signs of inflammation and inadequate response to NSAIDs.
• Off-Label / Investigational Uses:
• Potential use in other inflammatory autoimmune diseases under clinical trials, such as ulcerative colitis (approved in some regions), Crohn’s disease, and other immune-mediated conditions.

• Rheumatoid Arthritis and Psoriatic Arthritis:
• Adults: 15 mg orally once daily with or without food.
• Dose reduction to 15 mg every other day or temporary interruption may be considered for adverse events or specific clinical situations.
• Atopic Dermatitis:
• Adults and adolescents (≥12 years): 15 mg orally once daily.
• For severe cases, some guidelines allow 30 mg once daily under specialist supervision.
• Ankylosing Spondylitis / Non-radiographic Axial Spondyloarthritis:
• Adults: 15 mg orally once daily.
• Elderly:
• No initial dose adjustment required; monitor closely for adverse events.
• Pediatrics (<12 years):
• Safety and efficacy not established.
• Renal Impairment:
• No dose adjustment needed for mild to moderate impairment.
• Use with caution in severe impairment.
• Hepatic Impairment:
• Use with caution in mild to moderate impairment; no dose adjustment recommended.
• Not recommended in severe hepatic impairment.
• Administration:
• Oral tablets taken once daily, with or without food.

Upadacitinib is a selective Janus kinase (JAK) inhibitor with higher specificity for JAK1 over JAK2, JAK3, and TYK2. By inhibiting JAK1, it interferes with the JAK-STAT signaling pathway crucial for cytokine-mediated intracellular signaling involved in immune cell function and inflammation. This modulation reduces the activity of pro-inflammatory cytokines such as interleukins (IL-6, IL-12, IL-23), interferons, and others, leading to decreased inflammation and immune response in autoimmune diseases like rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis.

• Absorption:
• Rapidly absorbed orally with peak plasma concentrations reached within 2 to 4 hours.
• Absolute bioavailability approximately 80%.
• Distribution:
• Volume of distribution approximately 45 L.
• Plasma protein binding ~54%.
• Metabolism:
• Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6.
• Multiple metabolites formed, none significantly active.
• Elimination:
• Half-life approximately 9 to 14 hours.
• Eliminated mainly via feces (~38%) and urine (~24%).

• Pregnancy:
• Classified as pregnancy category C (FDA).
• Animal studies showed adverse effects on fetal development; no adequate human data available.
• Use only if potential benefits justify the risk.
• Lactation:
• Unknown if excreted in human milk.
• Breastfeeding is not recommended during treatment and for at least 2 days after the last dose.

• Janus kinase (JAK) inhibitor
• Targeted synthetic disease-modifying antirheumatic drug (tsDMARD)

• Known hypersensitivity to Upadacitinib or any formulation components.
• Active serious infections, including tuberculosis.
• Severe hepatic impairment.
• Use in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants (e.g., azathioprine, ciclosporin).

• Increased risk of serious infections (bacterial, viral, fungal, opportunistic).
• Screen for latent tuberculosis before initiation.
• Monitor for signs of infection during treatment.
• Risk of thrombosis including deep vein thrombosis and pulmonary embolism.
• Laboratory monitoring recommended: CBC, liver enzymes, lipid profile.
• Potential risk of malignancies, gastrointestinal perforation, and elevated liver enzymes.
• Use with caution in elderly patients or those with cardiovascular risk factors.
• Avoid live vaccines during treatment.

• Common:
• Upper respiratory tract infections
• Nasopharyngitis
• Nausea
• Elevated liver enzymes
• Increased creatine phosphokinase (CPK)
• Serious (Less Common):
• Serious infections (e.g., pneumonia, herpes zoster)
• Thromboembolic events
• Gastrointestinal perforation
• Malignancies (lymphoma, skin cancers)
• Cytopenias (anemia, neutropenia)

• CYP3A4 Inducers (e.g., rifampin, carbamazepine):
• May decrease Upadacitinib plasma concentration, reducing efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole):
• May increase plasma concentration, increasing risk of adverse effects.
• Immunosuppressants:
• Combination increases risk of infections; concomitant use not recommended.
• Live Vaccines:
• Should be avoided during and shortly after treatment.
• No significant food or alcohol interactions reported.

• FDA approved Upadacitinib for multiple indications, expanding beyond rheumatoid arthritis to atopic dermatitis, psoriatic arthritis, and axial spondyloarthritis.
• EMA and other regulatory agencies have issued similar approvals with specific dosing recommendations.
• Recent guidelines emphasize careful patient selection due to infection and thromboembolism risks.
• Updated safety warnings on risk of serious infections and thrombosis incorporated into prescribing information.
• Monitoring protocols and vaccination recommendations updated accordingly.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Keep out of reach of children.
• No refrigeration required.