Fixal

• Approved Indications:
• Moderate to severe active Rheumatoid Arthritis (RA): In adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
• Moderate to severe active Ulcerative Colitis (UC): For induction and maintenance of remission in adults who have had an inadequate response or intolerance to conventional or biologic therapies.
• Moderate to severe active Crohn’s Disease (CD): Approved in some regions for adult patients with inadequate response or intolerance to prior therapies.
• Off-label / Clinically Accepted Uses:
• Investigational use in other autoimmune or inflammatory disorders is ongoing, including psoriatic arthritis.

• Route: Oral.
• Adults:
• Rheumatoid arthritis: 200 mg once daily, with or without methotrexate.
• Ulcerative colitis: Induction dose typically 200 mg once daily for 10 weeks; maintenance dose 100 mg once daily.
• Crohn’s disease: Dose may vary, typically 200 mg once daily.
• Pediatrics:
• Safety and efficacy not established; use generally not recommended.
• Elderly:
• No specific dose adjustment necessary, but monitor for adverse effects.
• Renal impairment:
• Mild to moderate impairment: No dose adjustment required.
• Severe impairment or end-stage renal disease: Use with caution; limited data.
• Hepatic impairment:
• Mild to moderate impairment: No dose adjustment required.
• Severe impairment: Not recommended due to limited safety data.
• Administration Notes:
• Can be taken with or without food.
• Swallow whole with water.

Filgotinib maleate is a selective Janus kinase 1 (JAK1) inhibitor. By selectively inhibiting JAK1, filgotinib blocks the signaling pathways of pro-inflammatory cytokines that utilize the JAK-STAT pathway, such as interleukins and interferons. This results in downregulation of immune-mediated inflammatory responses, reducing inflammation, joint damage, and symptoms in autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease.

• Absorption: Rapid oral absorption; peak plasma concentrations reached within 2-3 hours.
• Bioavailability: Approximately 80%.
• Distribution: Volume of distribution ~ 300 L, moderate plasma protein binding (~55%).
• Metabolism: Primarily metabolized by carboxylesterases to an active metabolite with similar JAK1 selectivity.
• Active Metabolite: Exhibits similar pharmacological activity; prolongs therapeutic effect.
• Elimination: Excreted mainly via urine (≈85%), with minor fecal elimination.
• Half-life: Parent drug ~6 hours; active metabolite ~23 hours.
• Onset of action: Clinical effects observed within weeks of therapy initiation.

• Pregnancy: No well-controlled human studies available; animal studies have shown reproductive toxicity at high doses. Use only if benefits justify potential risks.
• Lactation: Unknown if excreted in human milk; breastfeeding is not recommended during treatment and for 4 weeks after discontinuation.

• Janus kinase (JAK) inhibitor.
• Targeted synthetic disease-modifying antirheumatic drug (tsDMARD).

• Known hypersensitivity to filgotinib or any excipients.
• Active serious infections (e.g., tuberculosis, sepsis).
• Severe hepatic impairment (due to lack of safety data).

• Increased risk of serious infections including tuberculosis, fungal infections, and viral infections.
• Monitor for signs of infection; discontinue if serious infection develops.
• Screen for latent tuberculosis prior to treatment initiation.
• Avoid use in patients with severe hepatic or renal impairment unless benefit outweighs risk.
• Monitor blood counts (CBC) regularly for cytopenias.
• Caution in patients at risk for thrombosis; JAK inhibitors have been associated with thromboembolic events.
• Risk of gastrointestinal perforation in patients with diverticulitis or on concomitant NSAIDs, corticosteroids.
• Avoid live vaccines during and shortly after treatment.
• Not recommended during pregnancy or breastfeeding unless clearly necessary.

• Common:
• Upper respiratory tract infections.
• Nausea.
• Headache.
• Elevated liver enzymes (mild).
• Increased creatinine kinase.
• Serious but less common:
• Serious infections.
• Herpes zoster reactivation.
• Thromboembolic events (deep vein thrombosis, pulmonary embolism).
• Cytopenias (anemia, neutropenia).
• Elevated lipid levels.
• Rare:
• Gastrointestinal perforation.
• Malignancies (rare reports with JAK inhibitors).

• Substrate of CYP3A4: strong CYP3A4 inducers (e.g., rifampicin) may reduce filgotinib levels; avoid or monitor therapy.
• No significant inhibition or induction of CYP450 enzymes by filgotinib.
• Concomitant immunosuppressants may increase infection risk.
• Avoid live vaccines during therapy.
• No significant interaction with food.

• FDA and EMA approvals expanding for use in moderate to severe ulcerative colitis.
• Updated safety warnings emphasize infection risk and thrombosis risk monitoring.
• Recent guidelines recommend pre-treatment screening for latent infections and regular blood monitoring during therapy.
• Dose adjustments being evaluated for special populations in ongoing studies.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Keep out of reach of children.