What are the precautions for filgotinib?

In clinical studies of filgotinib (Filgotinib), warnings and precautions such as infection, viral reactivation, malignant tumors, vaccination, cardiovascular risks, venous thromboembolism, embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity. It is not recommended to use filgotinib in combination with other potent immunosuppressives, such as azathioprine, cyclosporine, tacrolimus, biologic DMARDs (bDMARDs) or other Janus kinase (JAK) inhibitors, as the risk of increased immunosuppression cannot be excluded.

1. Infection: including serious infection. The most common serious infection reported with filgotinib was pneumonia; among opportunistic infections, tuberculosis, esophageal Candida infection, and cryptococcal infection have been reported with filgotinib. The risks and benefits of treatment should be considered before initiating filgotinib in patients who have chronic or recurrent infections, have been exposed to tuberculosis, have a history of serious or opportunistic infections, have lived in or traveled to areas with endemic tuberculosis or endemic mycoses, or have underlying conditions that may predispose them to infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after filgotinib therapy. If infection occurs during filgotinib therapy, the patient should be carefully monitored and filgotinib therapy should be temporarily interrupted if the patient does not respond to standard antimicrobial therapy. Once the infection is controlled, filgotinib therapy can be resumed. Because the incidence of serious infections is higher in people aged 75 and older, caution should be used when treating this population. Figotinib should not be used in patients with active tuberculosis, and in patients with latent tuberculosis, standard antimycobacterial therapy should be initiated prior to dosing.

2. Virus reactivation: including cases of herpes virus reactivation (such as herpes zoster). If a patient develops herpes zoster, filgotinib treatment should be temporarily discontinued until symptoms resolve. Screening for viral hepatitis and monitoring for reactivation should be performed according to clinical guidelines before initiating and during treatment with filgotinib. Patients who were positive for both hepatitis C antibodies and hepatitis C virus RNA were excluded from the clinical study. Patients who were positive for hepatitis B surface antigen or hepatitis B virusDNA were excluded from clinical studies.

3. Malignant tumors: Patients with rheumatoid arthritis are at increased risk of malignant tumors. Immunomodulatory drugs may increase the risk of malignancy. Malignancies have been observed in clinical studies with filgotinib. In patients with successfully treated non-melanoma skin cancer (The risks and benefits of filgotinib therapy should be considered before initiating treatment in patients with known malignancies other than NMSC or when considering continuing filgotinib therapy in patients who develop malignancy. For patients at increased risk of skin cancer, regular skin examinations are recommended.

4. Fertility: In animal studies with filgotinib, reduced fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed. The potential effects of filgotinib on human sperm production and male fertility are currently unknown. The reversibility of these potential effects is unknown. The potential risks of reduced fertility or infertility should be discussed with male patients before initiating treatment.

5. Vaccination: It is not recommended to use live vaccines during or immediately before filgotinib treatment. It is recommended that immunizations be updated in accordance with current immunization guidelines before initiating filgotinib therapy.

6. Cardiovascular risk: Patients with rheumatoid arthritis are at increased risk of cardiovascular disease. Patients should have risk factors (eg, hypertension, hyperlipidemia) managed as part of routine standard of care.

7. Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) events have been reported in patients receiving JAK inhibitors, including filgotinib. JAK inhibitors should be used with caution in patients with risk factors for DVT/PE, such as older age, obesity, a history of DVT/PE, or patients undergoing surgery and long-term immobilization. If clinical features of DVT/PE occur, filgotinib therapy should be discontinued, the patient should be promptly evaluated, and appropriate treatment should be initiated.

8. Embryo-Fetal Toxicity: According to animal study results, filgotinib may cause harm to the fetus, so filgotinib is contraindicated during pregnancy and lactation. It is recommended that women of childbearing potential must use effective contraception during drug treatment and for at least 1 week after stopping treatment.

9. Patients with rare hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this drug.