Formulary
Ponesimod: Indications, Dosing, Side Effects and Interactions
Ponesimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
MedNext Academy | 4 min read
Ponesimod: Indications, Dosing, Side Effects and Interactions
Ponesimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
Drug action
Ponesimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the central nervous system.
Indications and dose
**Multiple sclerosis (initiated under specialist supervision)**
- **Adult** (By Mouth): Initially 2 mg once daily on days 1-2, then increased to 3 mg once daily on days 3-4, then increased to 4 mg once daily on days 5-6, then increased in steps of 1 mg once daily from days 7-11, then increased to 10 mg once daily on days 12-14; maintenance 20 mg once daily from day 15 onwards, for re-initiation after treatment interruption-consult product literature.
Cautions
Administration of vaccinations; cerebrovascular disease (including transient ischaemic attack or stroke more than 6 months ago); chronic obstructive pulmonary disease; decompensated heart failure (more than 6 months ago); diabetes mellitus (increased risk of macular oedema); elderly (no information available); history of cardiac arrest; history of second-degree Mobitz type II AV block, third-degree AV block, sick sinus syndrome, or sino-atrial heart block; history of significant liver disease; history of uveitis (increased risk of macular oedema); immunosuppression or other risk factors for infection; patients receiving QT-prolonging or heart rate-lowering drugs, including beta-blockers and heart rate-lowering calcium-channel blockers; pulmonary fibrosis; recurrent syncope; risk of discontinuation effects, including disease rebound; severe respiratory disease; significant QT prolongation (QTc greater than 500 milliseconds) or other risk factors for QT prolongation; sinus bradycardia (heart rate below 55 beats per minute); uncontrolled hypertension; unstable ischaemic heart disease Cautions, further information Bradycardia and cardiac rhythm disturbance Ponesimod may cause transient bradycardia, AV conduction delays, and heart block after the first dose. It is not recommended in patients with the cardiovascular risks listed above unless the anticipated benefits outweigh the potential risks, and advice from a cardiologist (including monitoring advice) is sought before initiation. M Vaccinations Vaccination may be less effective during treatment. Live attenuated vaccines should be avoided during treatment; if they are required treatment should be stopped 1 week before and restarted 4 weeks after vaccination. Immunisation against varicella zoster is recommended prior to treatment in those without documented immunity. M
Contraindications
Active chronic infections; active malignancies; decompensated heart failure (requiring inpatient treatment) in the previous 6 months; heart failure (New York Heart Association class III or IV) in the previous 6 months; immunodeficiency; macular oedema; myocardial infarction in the previous 6 months; phototherapy with UV-B radiation or PUVA-photochemotherapy (increased risk of cutaneous neoplasm); second-degree Mobitz type II AV block, third-degree AV block, or sick sinus syndrome, unless pacemaker fitted; severe active infections; stroke (including transient ischaemic attack) in the previous 6 months; unstable angina in the previous 6 months
Side effects
Common or very common Anxiety; chest discomfort; cough; depression; dizziness; drowsiness; dyspepsia; dyspnoea; fatigue; fever; hypercholesterolaemia; hypertension; increased risk of infection; insomnia; joint disorders; ligament sprain; lymphopenia; macular oedema; migraine; numbness; pain; peripheral oedema; vertigo Uncommon Bradycardia; dry mouth; hyperkalaemia Frequency not known Atrioventricular block; neoplasms; seizure
Interactions
**Severe interactions:**
- No significant changes in pharmacokinetics of ponesimod or propranolol were observed.
**Other interactions (12):**
- Anti-neoplastic, immune-modulating, or immunosuppressive therapies Ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies.
- Anti-arrhythmic medicinal products, QT prolonging medicinal products, medicinal products that may decrease heart rate Ponesimod has not been studied in patients taking QT prolonging medicinal...
- Beta-blockers The negative chronotropic effect of co-administration of ponesimod and propranolol was evaluated in a dedicated pharmacodynamics safety study.
- The addition of ponesimod to propranolol at steady-state has an additive effect on HR effect.
- In a drug-drug interaction study, the up-titration regimen of ponesimod (see section 4.2) was administered to subjects receiving propranolol (80 mg) once daily at steady-state.
- Compared to ponesimod alone, the combination with propranolol after the first dose of ponesimod (2 mg) had a 12.4 bpm (90% CI: -15.6 to -9.1) decrease in mean hourly heart rate and at the first dose...
Pregnancy
Avoid-toxicity in animal studies. M
Breast feeding
Avoid-present in milk in animal studies. M
Hepatic impairment
Avoid in moderate to severe impairment (increased exposure). M
Medicinal forms
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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