Upacit XR

• Rheumatoid arthritis

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.

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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.

Strong CYP3A4 Inhibitors: Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors (such as ketoconazole). Upadacitinib should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors.Strong CYP3A4 Inducers: Upadacitinib exposure is decreased when co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect of Upadacitinib. Coadministration of Upadacitinib with strong CYP3A4 inducers is not recommended.

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

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.

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.

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.