Ponesimod

FDA label

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Titration Fixed 14-day up-titration (starter pack required); maintenance 20 mg QD starts Day 15

Renal Undefined

Hepatic Mild (Child-Pugh A): no adjustment. Moderate/severe (Child-Pugh B/C): not recommended

Instructions

• Swallow tablet whole; with or without food
• Before first dose: ECG, recent CBC with lymphocytes, LFTs (transaminases/bilirubin), fundus/macula exam, skin exam, VZV antibody test (vaccinate antibody-negative patients ≥1 month before starting); give live attenuated vaccines ≥1 month before initiation
• First-dose 4-hour monitoring (hourly pulse/BP, pre- and post-dose ECG) if sinus bradycardia (HR <55 bpm), first- or second-degree Mobitz I AV block, or MI/heart failure >6 months prior and stable
• If <4 consecutive doses missed: resume at first missed titration dose (during titration) or maintenance dose; if ≥4 doses missed: reinitiate at Day 1 with new starter pack (repeat first-dose monitoring if indicated)

Contraindications

• MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure within the last 6 months
• Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, or sino-atrial block, unless a functioning pacemaker is present

Cautions

• Infections — dose-dependent lymphocyte reduction to 30–40% of baseline; do not start with active infection; monitor during and 1–2 weeks after stopping
• Bradyarrhythmia and AV conduction delays on initiation — titration required; ECG before starting; cardiology consult for conduction abnormalities or HR-lowering co-medication
• Respiratory effects — decline in pulmonary function; spirometry if indicated
• Liver injury — LFTs before starting; discontinue if significant injury confirmed
• Increased blood pressure — monitor
• Cutaneous malignancies — baseline and periodic skin exams
• Fetal risk — effective contraception during and 1 week after stopping
• Macular edema — baseline and periodic fundus exams; diabetes and uveitis increase risk
• Posterior reversible encephalopathy syndrome
• Additive immunosuppression from prior immune therapies
• Severe increase in disability after stopping ponesimod

Adverse reactions

• Upper respiratory tract infection
• Hepatic transaminase elevation
• Hypertension (all ≥10%)

Pregnancy No adequate human studies; embryolethality and visceral/skeletal malformations in rats/rabbits at clinically relevant exposures — S1P1 receptor important in embryogenesis

Lactation No human data; ponesimod detected in offspring plasma of treated rats — weigh benefit of breastfeeding against maternal need and potential infant risk