Uptravi | Pharmacology Mentor

Generic Name

Uptravi

Selective S1P₁ agonist that sequesters circulating lymphocytes in secondary lymphoid organs.
Prevents lymphocyte egress into the systemic circulation and the central nervous system.
Resulting in a modest reduction of pathogenic immune surveillance and decreased inflammatory CNS lesions.

Route: Oral, once‑daily tablets.
Absorption: Tmax ≈ 2–4 h; ~100 % bioavailability with food.
Distribution: Highly protein‑bound (≥ 99 %).
Metabolism: Extensive CYP3A4‑mediated N‑dealkylation; hepatic microsomes.
Elimination: 80 % fecal, 20 % urinary; terminal half‑life ≈ 49 h (steady‑state ~6 days).
Drug interactions: Strong CYP3A4 inhibitors/inducers alter serum levels; caution with immunosuppressants (e.g., tacrolimus).

Pregnancy (Category X) – teratogenic in animal studies; avoid.
Active HBV/HCV infection – increased risk of viral reactivation.
Severe hepatic impairment (Child‑Pugh C).
Cardiovascular disease – baseline ECG required; risk of first‑dose bradycardia, atrioventricular block, and pulmonary hypertension.
Concurrent use with other S1P receptor modulators or immunosuppressants may be contraindicated.
Active infection at initiation – potential for infectious complications.

Initial dose: 10 mg PO qd (once daily).
Rapid‑start: For patients with no prior disease‑modifying therapy, commence 10 mg PO qd without a loading phase.
Maintenance: 10 mg PO qd once steady state is achieved (≈ 2 weeks).
Duration: 11‑month cycles; can be continuous if tolerable.
Tapering: May require dose reduction if adverse events occur; no defined taper; consult prescribing info.
Administration: Take with food to enhance absorption; avoid alcohol as it may potentiate bradycardia.

Common: Nasopharyngitis, headache, dizziness, palpitations, nasopharyngitis.
Serious:
Cardiac: first‑dose bradycardia, atrioventricular block.
Pulmonary: pulmonary hypertension, respiratory distress.
Hepatic: transaminase elevations; monitor LFTs.
Infection: opportunistic infections (e.g., CMV, PJP).
Eye: optic neuritis (rare), visual disturbances.

Baseline: CBC, ALT/AST, bilirubin, electrolytes, LFTs, ECG (30‑min Holter).
First dose monitoring: Continuous cardiac telemetry 24 h; bed rest >6 h.
Liver function: Every 3 weeks for the first 3 months, then monthly.
Lymphocyte count: Every 3 months; discontinue if < 0.5 × 10⁹/L.
Infection surveillance: Assess for symptoms of infection; baseline viral hepatitis panel.
Reproductive health: Confirm pregnancy test pre‑treatment and periodically thereafter.

First‑dose heart‑stopwatch: Because bradycardia is dose‑dependent, schedule the first dose when the patient is in the clinic; ensure at least 6 h post‑dose monitoring.
Avoid driving / machine operation until the first dose effects are ruled out.
CYP3A4 inhibitors/inducers (e.g., ketoconazole, rifampin) significantly alter ponesimod exposure—consider dose adjustment or discontinuation.
Pregnancy precautions: Discuss contraception for men and women; free‑breastfeeding therapy is contraindicated.
Combination therapy: When switching from another S1P modulator (e.g., fingolimod) use a washout period (≥ 5 months) to avoid overlapping immunosuppression.
Patient education: Emphasize signs of infection, liver dysfunction (jaundice, dark urine), and cardiovascular symptoms (blurred vision, faintness).