Baricitinib

Breast Feeding; Lactation; Milk, Human; Antirheumatic Agents; Enzyme Inhibitors; Janus Kinase Inhibitors; JAK Inhibitors; Signal Transduction Inhibitors; Protein Kinase Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Danger

H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P270, P271, P273, P280, P301+P317, P304+P340, P318, P319, P330, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 6 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In the large prelicensure clinical trials in rheumatoid arthritis, serum aminotransferase elevations occurred in up to 17% of baricitinib treated subjects compared to 11% in placebo recipients. The elevations were typically mild and transient and values above 3 times the upper limit of normal (ULN) occurred in 1% to 2% of patients. The elevations occasionally led to early discontinuations, but more often resolved even without dose adjustment. In prelicensure studies in rheumatoid arthritis, alopecia areata and other rheumatic and immune-mediated disorders, there were no instances of clinically apparent liver injury attributed to baricitinib. Since approval and more wide scale availability of baricitinib, there have been no published reports of hepatotoxicity associated with its use.

Baricitinib is generally considered a safe and well-tolerated medication. However, it increases the risk of severe infections due to its immunosuppressive properties. During clinical trials, the most frequently reported adverse events in alopecia areata patients included upper respiratory tract infections, acne vulgaris, headaches, urinary tract infections, and folliculitis. In addition, there is an increased incidence of herpes zoster infections.

L04AA37

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Baricitinib is a disease-modifying antirheumatic drug (DMARD) used to ameliorate symptoms and slow down the progression of rheumatoid arthritis. In animal models of inflammatory arthritis, baricitinib was shown to have significant anti-inflammatory effects but also led to the preservation of cartilage and bone, with no detectable suppression of humoral immunity or adverse hematologic effects. Baricitinib decreased the levels of immunoglobulins and serum C-reactive protein in patients with rheumatoid arthritis.

As members of the tyrosine kinase family, Janus kinases (JAKs) are intracellular enzymes that modulate signals from cytokines and growth factor receptors involved in hematopoiesis, inflammation, and immune cell function. Upon binding of extracellular cytokines and growth factors, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs). STATs modulate intracellular activity, including gene transcription of inflammatory mediators that promote an autoimmune response, such as IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ, GM-CSF, and interferons. The JAK-STAT pathway has been implicated in the pathophysiology of rheumatoid arthritis, as it is associated with an overproduction of inflammatory mediators. There are four JAK proteins: JAK 1, JAK 2, JAK 3 and TYK2. JAKs form homodimers or heterodimers and pair differently in different cell receptors to transmit cytokine signaling. Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 with less affinity for JAK3 and TYK2; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. Baricitinib inhibits the activity of JAK proteins and modulates the signaling pathway of various interleukins, interferons, and growth factors. It was also shown to decrease the proliferation of JAK1/JAK2 expression in mutated cells and induce cell apoptosis.