Saphnelo
Saphnelo
Generic Name
Saphnelo
Mechanism
- Selective JAK1/JAK2 inhibition: Blocks phosphorylation of STAT proteins → ↓ transcription of genes encoding cytokines, chemokines, and growth factors.
- Interferes with multiple inflammatory pathways: TNF‑α, IL‑6, IL‑15, IFN‑γ, and IL‑2 families, leading to decreased lymphocyte proliferation and cytokine production.
- Result: Reduced synovial inflammation, halts cartilage destruction, and mitigates systemic immune dysregulation in autoimmune diseases.
Pharmacokinetics
| Feature | Details |
| Administration | Oral tablet, 2 mg once daily (adjustable 1–4 mg). |
| Absorption | Rapid, peak plasma concentration 2–4 h post-dose; food does not significantly alter bioavailability. |
| Distribution | Protein‑binding ~15 % to serum albumin. |
| Metabolism | Mainly CYP3A4, with minor CYP2C9 involvement; UGT1A9 also contributes. |
| Elimination | Renal excretion (~90 % unchanged); hepatic metabolism low‑impact. |
| Half‑life | ~12 h (steady‑state). |
| Drug‑Drug Interactions | Potent CYP3A4 inducers (rifampin) ↑ clearance → ↓ efficacy; inhibitors (ketoconazole) ↑ exposure. |
Indications
- Rheumatoid Arthritis: Moderately to severely active disease in adults; may be used as monotherapy or with methotrexate.
- Ulcerative Colitis: Adults with moderate to severe active disease; adjunctive to conventional DMARDs.
- Alopecia Areata: Adults with severe alopecia areata not responding to conventional therapy.
Contraindications
- Contraindications: Active infection (especially tuberculosis), known hypersensitivity to baricitinib, severe hepatic impairment (Child‑Pugh C).
- Warnings:
- Infections: Elevated risk of bacterial, viral (herpes zoster), and opportunistic infections; screen for TB, hepatitis B/C before initiation.
- Thromboembolic Events: Pulmonary embolism, deep vein thrombosis, stroke (especially in >65 y, BMI >35 kg/m², or prior VTE).
- Malignancy: Rare malignancies; caution in patients with history of cancer or active malignancy.
- Hepatic Dysfunction: Monitor liver enzymes; reduce dose if ALT/AST >3× ULN.
- Pregnancy/Lactation: Category B; avoid if possible; contraceptive advised.
Dosing
- Rheumatoid Arthritis:
- Start with 2 mg PO daily.
- If inadequate response after ≥3 months, consider increasing to 4 mg daily; 1 mg daily is an alternative for mild disease or renal impairment.
- Ulcerative Colitis:
- 2 mg PO daily (3‑month course).
- Use cautiously with thiopurines or anti‑TNF agents.
- Alopecia Areata:
- 2 mg PO daily; evaluate at 3–4 months; taper off if remission.
- Renal impairment (<30 mL/min/1.73 m²): Reduce to 1 mg daily.
- Hepatic impairment: Avoid if Child‑Pugh B/C; monitor hepatic function regularly.
Instructions: Take with or without food; maintain consistent dosing schedule.
Adverse Effects
| Category | Examples |
| Common (≥10 %) | Upper respiratory tract infection, nasopharyngitis, headache, hypertension, nausea, diarrhea, increased serum creatine kinase. |
| Serious (≤10 %) | Serious infections (sepsis, community‑acquired pneumonia, invasive fungal), major adverse cardiovascular events (MI, stroke), pulmonary embolism, hepatic function abnormalities, malignancy, severe cutaneous adverse reactions. |
| Immunologic | Autoimmune cytopenias (e.g., thrombocytopenia), reactivation of latent hepatitis B. |
| Dermatologic | Recurrent herpes zoster, skin rash. |
Monitoring
- Baseline: CBC with differential, CMP, LFTs, lipid profile, hepatitis B/C serology, HIV, urine culture, TB screening (IGRA or interferon‑γ release assay).
- During Therapy:
- CBC and CMP every 3 months first year; every 6 months thereafter.
- Lipid profile annually (JAK inhibitors can raise LDL/HDL).
- Vaccinations: Ensure shingles vaccine (non‑live) and influenza before therapy.
- Infection surveillance: Promptly investigate fever, cough, new lesions.
- Renal/hepatic function: Reassess at each visit; adjust dosing accordingly.
- Dose adjustments: Discontinue if ALT/AST >3× ULN with symptoms; reduce dose if >2× ULN asymptomatic.
Clinical Pearls
- TB Screening is Non‑Negotiable: Positive IGRA warrants TB treatment before starting Saphnelo; repeat IGRA at 3 months if latent TB therapy just started.
- Herpes Zoster Prophylaxis: Consider recombinant zoster vaccine for adults >50 y irrespective of prior exposure; vaccine must be administered *before* baricitinib initiation.
- Renal & Hepatic Considerations: Use the *lowest effective dose* in renal impairment; monitor ALT/AST closely when co‑administered with hepatotoxic agents (e.g., cyclosporine).
- Weight Gain & Metabolic Effects: Patients may experience modest weight gain and altered lipid values; counsel on diet and regular lipid monitoring.
- Combination Therapy: When combined with TNF inhibitors or methotrexate, higher risk of infections; immunizations should be up‑to‑date and prophylactic antimicrobials considered in high‑risk settings.
- Patient Education: Emphasize strict adherence, timely reporting of fever or skin lesions, and contraceptive use due to potential teratogenicity.
- Treatment Discontinuation: Rapid taper not required; if drug is discontinued, monitor for immune reconstitution inflammatory syndrome (IRIS) manifestations, especially in TB‑positive patients.
--
• *This drug card is intended for educational use and should not replace individualized clinical judgment. Always refer to the latest prescribing information and guidelines for detailed dosing algorithms and safety updates.*