What is the recommended dosing regimen for Epuris (upadacitinib)?

Epuris (Upadacitinib) Dosing

The standard dose of upadacitinib is 15 mg once daily for rheumatoid arthritis, atopic dermatitis, and other approved indications, with no dose adjustment needed for renal impairment but contraindicated in severe hepatic impairment. 1

Standard Dosing by Indication

Rheumatoid Arthritis

• 15 mg once daily is the FDA and EMA approved dose for moderate to severe rheumatoid arthritis 1
• Can be used as monotherapy or in combination with methotrexate 1
• Effective in all RA populations: methotrexate-inadequate responders, biologic-inadequate responders, and methotrexate-naïve patients 1

Atopic Dermatitis

• 15 mg or 30 mg once daily depending on disease severity 1
• The 30 mg dose demonstrates highest efficacy for reducing EASI scores and was superior to dupilumab in head-to-head trials 1
• Reserved for moderate-to-severe patients who have failed other systemic therapies (immunosuppressants, corticosteroids, biologics) 1

Ulcerative Colitis

• Induction: 45 mg once daily for 8 weeks 1
• Maintenance: 15 mg or 30 mg once daily after achieving clinical response 1

Dose Adjustments and Contraindications

Hepatic Impairment

• No adjustment needed for mild to moderate hepatic impairment 1
• Contraindicated in severe hepatic impairment (Child-Pugh C) 1

Renal Impairment

• No dose adjustment required for any degree of renal impairment 1
• This distinguishes upadacitinib from other JAK inhibitors like baricitinib, which requires dose reduction with creatinine clearance 30-60 mL/min 1

Critical Safety Considerations

High-Risk Populations Requiring Caution

The European Medicines Agency mandates that JAK inhibitors should only be used when no suitable alternatives exist in: 1, 2

• Patients ≥65 years of age
• Those with cardiovascular risk factors (increased MACE risk)
• Current or long-term past smokers
• Those at increased risk of malignancy
• Patients with VTE risk factors (thromboembolism concerns)

Baseline Screening Requirements

Before initiating upadacitinib: 1

• Screen for tuberculosis, hepatitis B, hepatitis C, and pregnancy
• Check complete blood count with differential
• Obtain liver enzymes and renal function
• Assess lipid panel
• Administer recombinant zoster vaccine (Shingrix) prior to treatment initiation

Monitoring Protocol

• CBC with differential and liver enzymes: at baseline, then per routine management 1
• Lipid panel: at 12 weeks after initiation 1
• Monitor for herpes zoster infection (increased risk versus comparators) 3, 4
• Watch for signs of VTE (chest pain, leg swelling, shortness of breath) 1, 3

Formulation and Administration

• Extended-release (ER) formulation enables once-daily dosing 5
• Food effect is minimal: high-fat meal increases exposure by only 17-20%, so can be taken with or without food 5
• Steady state achieved by day 4 of once-daily dosing 5
• Time to peak concentration: 2-4 hours 5

Drug Interactions

• Avoid strong CYP3A4 inducers (upadacitinib is a CYP3A4 substrate) 4
• No significant interactions with methotrexate when used in combination 1

Common Pitfalls to Avoid

• Do not use 30 mg dose in RA: only the 15 mg dose is approved for rheumatoid arthritis; 30 mg is reserved for atopic dermatitis and ulcerative colitis maintenance 1
• Do not overlook cardiovascular risk stratification: the ORAL surveillance study with tofacitinib showed increased MACE and malignancy in high-risk RA patients, leading to class-wide warnings 1, 2
• Do not skip zoster vaccination: herpes zoster rates are consistently elevated with upadacitinib versus comparators 3, 4
• Do not assume dose reduction is needed for renal impairment: unlike baricitinib, upadacitinib requires no renal dose adjustment 1