Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderate to severe active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.

The recommended dose of Upadacitinib is 15 mg once daily. Upadacitinib may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs. Avoid initiation or interrupt Upadacitinib if absolute lymphocyte count is less than 500 cells/mm³, absolute neutrophil count is less than 1000 cells/mm³ or hemoglobin level is less than 8 g/dL.

Pediatric Use: The safety and efficacy of Upadacitinib in children and adolescents aged 0 to 18 years have not yet been established. No data are available.

Adverse reactions (greater than or equal to 1%) are: upper respiratory tract infections, nausea, cough, and pyrexia.

Overdose Effects

Upadacitinib was administered in clinical trials up to doses equivalent in daily AUC to 60 mg extended-release once daily. Adverse events were comparable to those seen at lower doses and no specific toxicities were identified. Approximately 90% of upadacitinib in the systemic circulation is eliminated within 24 hours of dosing (within the range of doses evaluated in clinical studies). In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate treatment.

• Serious Infections: Avoid use of Upadacitinib in patients with active, serious infection, including localized infections.
• Malignancy: Consider the risks and benefits of Upadacitinib treatment prior to initiating therapy in patients with a known malignancy.
• Thrombosis: Consider the risks and benefits prior to treating patients who may be at increased risk of thrombosis. Promptly evaluate patients with symptoms of thrombosis and treat appropriately.
• Gastrointestinal Perforations: Use with caution in patients who may be at increased risk.
• Laboratory Monitoring: Recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids.
• Embryo-Fetal Toxicity: Upadacitinib may cause fetal harm based on animal studies. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.
• Vaccinations: Avoid use of Upadacitinib with live vaccines.

Pregnancy & Lactation

The limited human data on use of Upadacitinib in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. Based on animal studies, upadacitinib has the potential to adversely affect a developing fetus. Advise not to breastfeed.