Filgotinib Maleate

Filgotinib Maleate 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.

Filgotinib preferentially inhibited the activity of JAK1 and showed >5-fold higher potency for JAK1 over JAK2, JAK3 and TYK2.

• Rheumatoid Arthritis: Used for moderate to severe active RA in patients who have responded inadequately to, or are intolerant to DMARDs.
• Ulcerative Colitis: Used for moderately to severely active UC in patients who had inadequate response to conventional therapy or a biologic agent.

Adenosine triphosphate (ATP)-competitive and reversible inhibitor

JAK Inhibitor (JAK1 Selective)

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. Filgotinib preferentially inhibited the activity of JAK1.

Filgotinib inhibits JAK1 to prevent phosphorylation and activation of STATs, modulating inflammatory cytokine signaling pathways.

Adult Dose (Oral):

• Rheumatoid Arthritis: 200 mg tablet once a day.
• Ulcerative Colitis: 200 mg once daily; discontinue if no therapeutic benefit after 22 weeks.
• High-risk patients (VTE, MACE, malignancy): Maintenance: 100 mg once daily; may escalate to 200 mg in case of flare.

Elderly (>=65 years, RA): 100 mg once daily; may escalate to 200 mg if insufficient control.

Elderly (UC, >=65 years): Induction: 200 mg/day; Maintenance: 100 mg/day; not recommended in patients >=75 years.

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. May be taken with or without food.

If you miss a dose, take it as soon as possible; however, if it is almost time for your next dose, skip the missed dose.

Common Side Effects:

• Nausea
• Upper respiratory tract infection (URTI)
• Urinary tract infection (UTI)
• Dizziness

Precautions:

• Immunosuppressive medicinal products: Combination with azathioprine, ciclosporin, tacrolimus, bDMARDs or other JAK inhibitors not recommended.
• Infections: Serious infections (pneumonia, TB, esophageal candidiasis, cryptococcosis) reported; herpes zoster requires temporary interruption.
• Malignancy: RA patients have increased risk; immunomodulatory medicinal products may increase risk.
• Fertility: Animal studies showed histopathological effects on male reproductive organs.
• Vaccinations: Live vaccines not recommended.
• Lipids: Dose-dependent increase in total cholesterol, HDL, and LDL.
• Venous thromboembolism: Consider risks and benefits in patients at increased risk of thrombosis.

Contraindications:

• Hypersensitivity
• Active tuberculosis (TB) or active serious infections
• Pregnancy

Drug Interactions:

• CES2 Inhibitors (fenofibrate, carvedilol, diltiazem, simvastatin): Clinical relevance unknown.

Food Interactions: May be taken with or without food. Caution with alcohol.

Use in Pregnancy: Category D; animal studies showed reproductive toxicity; contraindicated during pregnancy; women of childbearing potential must use effective contraception during and for at least 1 week after cessation.

Use in Lactation: It is unknown whether filgotinib is excreted in human milk; should not be used during breastfeeding.

Pediatric Use: Safety and efficacy not established in patients below 18 years.

Geriatric Use: Not recommended in patients >=75 years (no data); 65-74 years: RA 100 mg/day, UC induction 200 mg/day and maintenance 100 mg/day.

Renal Impairment: Mild: no adjustment; moderate-severe: 100 mg once daily recommended.

Hepatic Impairment: Mild-moderate: no dose adjustment required.

Overdose: Doses up to 450 mg without dose-limiting toxicity in clinical studies; in case of overdose, general supportive measures should be given.

Storage: Do not store above 25 degree C. Protect from light. Keep out of reach of children.

Filgotinib Maleate