What is the dosage and usage of Upadacitinib (Janus kinase inhibitor) for treating inflammatory conditions?

Upadacitinib Dosage and Usage for Inflammatory Conditions

Upadacitinib is typically administered at a dose of 15 mg once daily for most inflammatory conditions, with dose adjustments required for drug interactions and organ dysfunction. 1

Approved Indications and Standard Dosing

Upadacitinib is a selective Janus kinase 1 (JAK1) inhibitor approved for several inflammatory conditions:

• Rheumatoid Arthritis (RA): 15 mg once daily 1, 2
• Psoriatic Arthritis (PsA): 15 mg once daily 1, 3
• Ankylosing Spondylitis (AS): 15 mg once daily 1
• Atopic Dermatitis: 15-30 mg once daily (with 30 mg providing approximately 20% greater efficacy) 4
• Ulcerative Colitis (UC): Dosing varies by indication 5
• Crohn's Disease (CD): Dosing varies by indication 5

Metabolism and Pharmacokinetics

Understanding upadacitinib's metabolism is crucial for proper dosing:

• Predominantly undergoes hepatic oxidation
• Minor metabolism via CYP3A4 pathway
• Approximately 20% renal excretion 1
• Extended-release formulation allows for once-daily dosing 2

Dose Adjustments

Drug Interactions

• Rifampicin (used in TB treatment): Increases hepatic metabolism of upadacitinib; consider dose increase 1
• Ketoconazole: Inhibits upadacitinib metabolism; dose reduction suggested 1

Organ Dysfunction

• Severe hepatic disease (Child-Pugh C): Upadacitinib should not be used 1
• Severe renal disease (CrCl <30 mL/min): No specific dosage reduction is currently recommended for upadacitinib, unlike other JAK inhibitors such as tofacitinib and baricitinib 1

Contraindications and Special Considerations

1. Severe active infections: Serious infection rates with upadacitinib are comparable to adalimumab, with higher rates at higher doses 1, 5

2. Malignancy: No specific malignancy signal has been demonstrated in clinical trials and registries, but shared decision-making is recommended for patients with:

   • Recent malignancy
   • Uncontrolled malignancy
   • Ongoing chemotherapy including checkpoint inhibitors 1

3. Pregnancy and lactation: Limited data available; contraception is advised for both female and male patients 1

4. Age considerations: Patients over 65 years with cardiovascular risk factors may have increased risk of serious infections 1, 5

Efficacy Profile

• In RA, upadacitinib has shown similar remission rates regardless of patient population (methotrexate-naïve, methotrexate-failure, or biologic failure) 2
• In PsA, exposure-response analyses predict robust efficacy with the 15 mg daily regimen 3
• In head-to-head trials, upadacitinib plus methotrexate was superior to adalimumab in methotrexate-inadequate responders 2, 6

Safety Considerations

• Most studies suggest no statistically significant difference in safety outcomes compared to other active treatments or placebo 5
• Safety profile generally consistent with other JAK inhibitors 2
• Shallow relationships with plasma exposures were observed for serious infections and hemoglobin decrease at the 15 mg dose 3

Monitoring Recommendations

• Monitor for infections, particularly in patients over 65 years
• Monitor hemoglobin levels, as decreases may occur
• Consider dose adjustments when using medications that affect CYP3A4 metabolism

Remember that while upadacitinib is selective for JAK1, its safety profile appears similar to less-selective JAK inhibitors, so appropriate monitoring is essential 6.