Upadacitinib Safety Considerations

Serious Cardiovascular and Thrombotic Risks

The European Medicines Agency recommends that upadacitinib should only be used in patients aged ≥65 years if no suitable alternatives exist, due to increased risk of major cardiovascular problems 1, 2
Upadacitinib carries significant cardiovascular and thrombotic risks, requiring careful patient selection, particularly avoiding use in patients ≥65 years, current/former smokers, or those with cardiovascular risk factors unless no alternatives exist 1, 2
Numerically increased rates of venous thromboembolism (VTE) observed in clinical trials, primarily with the 15 mg once daily dose 1, 4
Patients with prior VTE history have up to 10-fold increased risk 1
Risk factors for VTE include age, high BMI, immobilization, surgery, Cox-2 inhibitor use, and prior VTE history 1

Mandatory screening for latent tuberculosis before initiation using interferon-gamma release assay or tuberculin skin test is recommended 5
Screen for viral hepatitis before treatment 5
Recombinant zoster vaccine (Shingrix) should be administered before initiating therapy 5

Gastrointestinal perforation has been reported in clinical trials, possibly a class effect of JAK inhibitors 1, 4
Use with caution in patients at increased risk, including those with a history of diverticulitis, concomitant NSAID use, or concomitant glucocorticoid use 1, 4

Interrupt treatment if absolute neutrophil count <1000 cells/mm³ or absolute lymphocyte count <500 cells/mm³ 3, 5
Hemoglobin decreases ≤20 g/L and levels ≥90 g/L do not require dose adjustment 4
Hemoglobin <80 g/L (confirmed by repeat testing) should lead to dose interruption 7
Lipid profile should be checked at baseline and at 3 months 4, 5

Mandatory laboratory monitoring schedule includes baseline, 1 month, 3 months, and every 3 months thereafter, with tests including complete blood count, comprehensive metabolic panel, and lipid profile 4, 5

Contraindicated in pregnancy; teratogenic in animal studies 8
Do not use with severe hepatic disease (Child-Pugh C) 8
No dosage reduction currently recommended for upadacitinib with renal impairment, though 20% undergoes renal excretion 8

Do not initiate in patients with active serious infections 5
Do not fail to complete tuberculosis screening and hepatitis screening before initiation 5
Do not assume absence of symptoms equals absence of latent tuberculosis 5
Do not overlook cardiovascular risk assessment in older patients 6