Product Description

**Upanib (Upadacitinib) Summary**

**Indications**

* **Rheumatism & Spondyloarthritis:** Adults with active rheumatoid arthritis (RA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) who had an inadequate response or intolerance to one or more TNF blockers.

* **Psoriatic & Juvenile Arthritis:** Adults and pediatric patients $\ge$2 years with active psoriatic arthritis (PsA) or polyarticular juvenile idiopathic arthritis (pJIA) after inadequate TNF blocker response/intolerance.

* **Atopic Dermatitis:** Refractory, moderate to severe cases in adults and adolescents $\ge$12 years ($\ge$40 kg) not adequately controlled by other systemic agents or biologics.

* **Inflammatory Bowel Disease (IBD):** Adults with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) who had an inadequate response or intolerance to TNF blockers.

**Mechanism & Pharmacology**

* **Class:** Janus kinase (JAK) inhibitor.

* **Action:** Selectively inhibits intracellular JAK enzymes, blocking the phosphorylation and activation of Signal Transducers and Activators of Transcription (STATs). This downregulates cytokine signaling involved in systemic inflammation and immune-mediated cell function.

**Dosage & Administration**

* **RA, PsA, AS, nr-axSpA, & pJIA ($\ge$30 kg):** 15 mg once daily.

* **Atopic Dermatitis:**

* *Ages 12–64 years ($\ge$40 kg):* Initiate at 15 mg once daily; may increase to 30 mg once daily if response is inadequate (discontinue if 30 mg fails).

* *Adults $\ge$65 years:* 15 mg once daily.

* **Ulcerative Colitis:**

* *Induction:* 45 mg once daily for 8 weeks.

* *Maintenance:* 15 mg once daily (30 mg once daily may be considered for severe/refractory disease; discontinue if 30 mg fails).

* **Crohn's Disease:**

* *Induction:* 45 mg once daily for 12 weeks.

* *Maintenance:* 15 mg once daily (30 mg once daily may be considered for severe/refractory disease; discontinue if 30 mg fails).

**Key Interactions**

* **Strong CYP3A4 Inhibitors (e.g., Ketoconazole):** Increases upadacitinib concentration; use with caution.

* **Strong CYP3A4 Inducers (e.g., Rifampin):** Decreases upadacitinib concentration, reducing efficacy; co-administration is not recommended.

**Contraindications & Warnings**

* **Active Serious Infections:** Avoid starting treatment during active, severe localized or systemic infections.

* **Malignancy & Thrombosis:** Exercise caution in patients with known malignancies or elevated risk for blood clots (DVT/PE).

* **Gastrointestinal Perforation:** Caution in patients at increased risk for GI perforations.

* **Vaccinations:** Avoid administration of live vaccines concurrently.

* **Pregnancy & Lactation:** Potential fetal harm based on animal data; effective contraception is required during treatment. Breastfeeding is not recommended.

* **Organ Impairment:**

* *Hepatic:* Not recommended in severe hepatic impairment.

* *Renal:* Dose adjustments are required for severe renal impairment in AD, UC, and CD (max 15 mg/day for AD; 30 mg induction / 15 mg maintenance for UC/CD). Not recommended in end-stage renal disease (ESRD) for AD, UC, or CD.

**Side Effects & Monitoring**

* **Common Adverse Reactions:** Upper respiratory tract infections, acne, herpes zoster, herpes simplex, headache, cough, nausea, pyrexia, weight gain, increased blood CPK, and elevated liver enzymes.

* **Laboratory Monitoring:** Periodically check baseline and on-treatment levels of lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids.

**Storage**

* Store below 25°C protected from light. Keep out of reach of children.