Indications
Rheumatoid arthritis : Filgotinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Filgotinib may be used as monotherapy ... Read more Rheumatoid arthritis : Filgotinib is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Filgotinib may be used as monotherapy or in combination with methotrexate (MTX). Ulcerative colitis : Filgotinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent.
Composition
Pharmacology
Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane. JAK1 is important in mediating inflammatory cytokine signals, JAK2 in mediating myelopoiesis and erythropoiesis and JAK3 plays critical roles in immune homeostasis and lymphopoiesis. Within the signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Filgotinib modulates these signalling pathways by preventing the phosphorylation and activation of STATs. In biochemical assays, filgotinib preferentially inhibited the activity of JAK1 and showed >5-fold higher potency of filgotinib for JAK1 over JAK2, JAK3 and TYK2.
Dosage & Administration
Rheumatoid arthritis : The recommended dose of Filgotinib is 200 mg tablet once a day. Ulcerative colitis : The recommended dose of Filgotinib is 200 mg once daily. Patients who have not shown any therapeutic benefit after 22 weeks of treatment should discontinue Filgotinibib. In adults at higher risk of venous thromboembolism, major adverse cardiovascular events and malignancy, the recommended dose for maintenance treatment is 100 mg once daily. In case of flare of the disease, the dose may be escalated to 200 mg once daily. For long term treatment, the lowest effective dose should be used.
Contraindications
Hypersensitivity to the active substance or to any of the excipients Active tuberculosis (TB) or active serious infections Pregnancy
Side Effects
The most frequently reported adverse reactions are nausea, upper respiratory tract infection (URTI), urinary tract infection (UTI), dizziness etc.
Pregnancy & Lactation
Use in Pregnancy : There are no or limited amount of data from the use of filgotinib in pregnant women. Studies in animals have shown reproductive toxicity. Based on findings in animals, filgotinib may cause fetal harm and is therefore contraindicated during pregnancy. Women of childbearing potential / Contraception : Women of childbearing potential have to use effective contraception during and for at least 1 week after cessation of filgotinib treatment. Lactation : It is unknown whether filgotinib is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. Therefore, filgotinib should not be used during breast-feeding.
Precautions & Warnings
Immunosuppressive medicinal products : Combination of filgotinib with other potent immunosuppressants such as azathioprine, ciclosporin, tacrolimus, biologic DMARDs (bDMARDs) or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections : Infections, including serious infections, have been reported in patients receiving filgotinib. The most frequent serious infection reported with filgotinib was pneumonia. Among opportunistic infections, TB, oesophageal candidiasis, and cryptococcosis were reported with filgotinib. Viral reactivation : Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies. If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed in accordance with clinical guidelines before starting and during treatment with filgotinib. Malignancy : The risk of malignancies is increased in patients with rheumatoid arthritis. Immunomodulatory medicinal products may increase the risk of malignancies. Fertility : In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed. Vaccinations : Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. Lipids : Treatment with filgotinib was associated with dose-dependent increase in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low-density lipoprotein (LDL) levels were slightly increased. Venous thromboembolism : Consider the risks and benefits prior to treating patients with filgotinib, who may be at increased risk of thrombosis. Promptly evaluate patients with symptoms of thrombosis and treat appropriately.
Therapeutic Class
Adenosine triphosphate (ATP)-competitive and reversible inhibitor
Storage Conditions
Do not store above 25°C. Protect from light. Keep out of reach of children.