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

Upadacitinib Dosage and Usage for Inflammatory Conditions

Upadacitinib is recommended at a standard dose of 15 mg once daily for treating rheumatoid arthritis and other approved inflammatory conditions. 1

Approved Indications and Standard Dosing

Upadacitinib is approved for several inflammatory conditions with the following dosages:

• Rheumatoid Arthritis (RA): 15 mg once daily 1
• Psoriatic Arthritis (PsA): 15 mg once daily 2
• Ankylosing Spondylitis (AS): 15 mg once daily 3
• Atopic Dermatitis (AD): 15 mg or 30 mg once daily (higher dose used in AD only) 3
• Ulcerative Colitis (UC): 45 mg for induction, followed by 15 mg for maintenance 4
• Crohn's Disease (CD): Dosing similar to UC with higher induction dose followed by maintenance dose 4

Metabolism and Drug Interactions

Upadacitinib primarily undergoes hepatic oxidation with minor CYP metabolism and approximately 20% renal excretion 1. Important drug interactions to consider:

• Strong CYP3A4 inhibitors (e.g., ketoconazole): Increase upadacitinib exposure by 75% - consider dose reduction 5
• Strong CYP3A4 inducers (e.g., rifampin): Decrease upadacitinib exposure by 61% - coadministration not recommended 5
• Rifampin when used for TB prophylaxis/treatment: Consider dose increase of upadacitinib 1

Dose Adjustments for Special Populations

1. Renal impairment:

   • Severe renal disease (CrCl <30 mL/min): No specific dose adjustment recommended for upadacitinib, unlike tofacitinib or baricitinib 1
   • Mild to moderate renal impairment: Estimated 10-22% higher AUC compared to normal renal function 6

2. Hepatic impairment:

   • Severe hepatic disease (Child-Pugh C): Upadacitinib should not be used 1

3. Pregnancy and lactation:

   • Contraindicated during pregnancy due to potential risk to the fetus 5
   • Not recommended during breastfeeding; advise waiting at least 6 days (approximately 10 half-lives) after the last dose before breastfeeding 5

Safety Considerations

1. Infections:

   • Serious infection rates comparable to adalimumab, with higher rates at higher doses 1
   • Contraindicated in patients with severe active infections, including latent TB and opportunistic infections 1

2. Thromboembolic risk:

   • Use with caution in patients with history of venous thromboembolism (VTE) events 1
   • Monitor for signs and symptoms of VTE during treatment 3

3. Other safety considerations:

   • Higher rates of herpes zoster compared to active comparators 3
   • Elevated creatine phosphokinase levels may occur 3
   • Monitor for malignancies, though no specific signal has been observed in clinical trials 1, 3

Long-term Safety Profile

Long-term safety data across 15,425 patient-years of exposure shows upadacitinib is generally well-tolerated across RA, PsA, AS, and AD 3. Rates of treatment-emergent adverse events leading to discontinuation were similar across diseases (4.5-5.4 events/100 patient-years) 3.

Clinical Efficacy

Upadacitinib has demonstrated consistent clinical response rates across different patient populations, including methotrexate-naïve, methotrexate-failure, or biologic failure patients 7. In head-to-head trials, upadacitinib plus methotrexate has shown superiority to adalimumab with background methotrexate in patients with inadequate response to methotrexate 7.

Common Pitfalls and Caveats

1. Drug interactions: Failure to adjust dosing with CYP3A4 inhibitors or inducers can lead to under or over-exposure
2. Infection risk: Carefully screen for latent TB and active infections before initiating therapy
3. Age considerations: Higher risk of serious infections in patients over 65 years, particularly with higher doses
4. Pregnancy planning: Advise a 4-week gap after the last dose if pregnancy is being contemplated 1
5. Laboratory monitoring: Regular monitoring of complete blood count, liver enzymes, and lipids is recommended

Upadacitinib offers an effective oral option for various inflammatory conditions with a generally favorable benefit-risk profile when used at the recommended dosages and with appropriate patient selection.