Filgotinib instructions

1. Name: filgotinib, filgotinib, filgotinib, fillotinib, Jyseleca

2. Indications:

1. Rheumatoid arthritis (RA): Filgotinib (Filgotinib) is suitable for one or more conditions that alleviate the disease. For the treatment of moderately to severely active rheumatoid arthritis in adult patients with inadequate response to or intolerance to antirheumatic drugs (DMARDs), can be used as monotherapy or in combination with methotrexate (MTX).

2. Ulcerative colitis(UC):Figotinib is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients who have insufficient response, loss of response, or intolerance to conventional treatments or biologic agents.

3. Usage and dosage:

1. Recommended dose: The recommended dose of filgotinib is 200mg once daily. It can be taken with or without food. Whether the tablets can be divided, crushed, or chewed has not been studied and it is recommended that the tablets be swallowed whole.

2. Dose adjustment: For patients aged 75 years and above, the starting dose is 100 mg once a day. If a patient develops a serious infection, treatment should be interrupted until the infection is controlled. Patients with moderate or severe renal impairment (creatinine clearance [CrCl] 15 to <60 mL/min) are advised to take 100 mg of filgotinib once daily.

4. Adverse reactions:

In clinical studies of filgotinib, the most common side effects were nausea, upper respiratory tract infection (nose and throat infection), urinary tract infection, dizziness, and lymphopenia.

5. Storage:

Store filgotinib in its original packaging to protect it from moisture. Keep the bottle tightly closed.

6. Taboo:

Figotinib is contraindicated in the following patients:

1. For active substancesPatients who are allergic to Filgotinib and any of its excipients;

2. Patients with active pulmonary tuberculosis or active severe infection;

3. Pregnancy.

7. Special groups:

1. Women: According to the results of animal studies, filgotinib may cause harm to the fetus, so patients are prohibited from using filgotinib during pregnancy and lactation. It is recommended that women of childbearing potential must use effective contraceptive measures during drug treatment and for at least 1 week after stopping treatment.

8. Mechanism of action:

Figotinib is an adenosine triphosphate (ATP) competitive and reversible JAK family inhibitor. JAKs are intracellular enzymes that transmit signals resulting from the interaction of cytokines or growth factor receptors on the cell membrane. JAK1 is important in mediating inflammatory cytokine signaling, and JAK2 is important in mediating myelopoiesis and erythropoiesis. JAK3 plays a key role in immune homeostasis and lymphopoiesis. In signaling pathways, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs), which regulate intracellular activities, including gene expression.

Figotinib regulates these signaling pathways by preventing the phosphorylation and activation of STATs. In biochemical assays, filgotinib preferentially inhibited the activity of JAK1 and was shown to be more than 5 times more potent against JAK1 than JAK2, JAK3, and TYK2. In human cell assays, filgotinib preferentially inhibits JAK1/JAK3-mediated signaling downstream of heterodimeric cytokine receptors for interleukin (IL)-2, IL-4 and IL-15, JAK1/2-mediated IL-6, and JAK1/TYK2-mediated type I interferons, with functional selectivity over cytokine receptors signaling through JAK2 or JAK2/TYK2 pairs. The main metabolite of filgotinib, GS-829845, is approximately 10-fold less active than filgotinib in in vitro assays while exhibiting similar preferential JAK1 inhibitory activity. In an in vivo rat model, overall pharmacodynamic effects were primarily driven by metabolites.

9. Overdose:

In clinical studies, filgotinib has been administered at doses up to following single and once-daily dosing.450mg, no dose-limiting toxicities. Adverse effects were comparable to those observed at lower doses, and no specific toxicities were noted. Pharmacokinetic data following a single dose of 100 mg of filgotinib in healthy subjects indicate that approximately 50% of the administered dose is eliminated within 24 hours and 90% of the administered dose is eliminated within 72 hours. In the event of overdose, it is recommended that patients be monitored for signs and symptoms of adverse reactions. Treatment of filgotinib overdose includes general supportive measures, including monitoring of vital signs and observation of the patient's clinical status. It is unknown whether filgotinib can be removed by dialysis.