PONESIMOD TAB,ORAL
Clinical Criteria Summary
Indication
- Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (aSPMS) in adults
Dosing & Administration
- Oral tablets taken once daily
- Starter pack includes 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, and 10mg tablets for titration, plus 20mg maintenance tablets
- Titration starts at 2mg/d over 14 days to a target dose of 20mg/d
Contraindications
- Recent myocardial infarction, unstable angina, stroke or TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure
- Mobitz type II second-degree, third-degree AV block, sick sinus syndrome, or sino-atrial block (unless patient has a functioning pacemaker)
Warnings, Precautions & Monitoring Requirements
- Infections and lymphocytopenia: Do not initiate in patients with active infection; check CBC and ZVZ antibodies before treatment; monitor for infection during treatment and 1–2 weeks after discontinuation
- Bradycardia and AV conduction delays: Titration is required at initiation; check ECG to assess for preexisting cardiac conduction abnormalities before treatment; avoid use with other medications that decrease heart rate
- Missed dose: Patients should re-titrate if they miss more than three consecutive doses
- Pulmonary function: Check PFTs if clinically indicated; use with caution in patients with a history of severe respiratory disease
- Liver injury: Check LFTs before treatment initiation; discontinue if significant liver injury is confirmed (ALT or conjugated bilirubin ≥2x ULN, or combined increase of AST, AP, and total bilirubin with one >2x ULN)
- Blood pressure: Monitor BP during treatment due to risk of persistent elevations
- Cutaneous malignancy: Periodic skin examination is recommended
- Fetal risk: Patients of childbearing potential should use effective contraception during treatment and for 1 week after discontinuation; avoid during pregnancy; consider risks and benefits for lactating patients
- Macular edema: Recommend ophthalmic evaluation prior to treatment and if vision changes occur; regular ophthalmic evaluations including examination of the fundus and macula for patients with a history of diabetes or uveitis
- PRES: Caution is advised due to rare reports with other S1P receptor modulators
- Disease rebound: Severe increase in disability after stopping has been reported; caution is advised when discontinuing
Special Populations
- Geriatric: Patients aged 65 years and older have been excluded from clinical trials; caution is advised
- Hepatic impairment: Avoid in patients with moderate or severe hepatic impairment (Child-Pugh class B and C); no dose adjustment recommended for mild hepatic impairment (Child-Pugh class A)
Clinical Considerations & Place in Therapy
- First-dose cardiac monitoring is not required for patients with low cardiac risk
- No genotype testing is required prior to therapy initiation
- No additional concerning drug interactions beyond those described for the S1P receptor modulator class
- Shorter elimination half-life compared to other agents requires repeat dose titration if more than 3 consecutive doses are missed