Formulary
Siponimod: Indications, Dosing, Side Effects and Interactions
Siponimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
MedNext Academy | 3 min read
Siponimod: Indications, Dosing, Side Effects and Interactions
Siponimod is a sphingosine-1-phosphate receptor modulator, which prevents movement of lymphocytes out of lymph nodes, thereby limiting inflammation in the...
Drug action
Siponimod 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 [secondary progressive, with active disease] (initiated by a specialist)**
- **Adult** (By Mouth): Initially 0.25 mg once daily on days 1 and 2, followed by 0.5 mg once daily on day 3, followed by 0.75 mg once daily on day 4, followed by 1.25 mg once daily on day 5, dose to be taken in the morning for the first 5 days; maintenance 2 mg once daily from day 6 onwards, in patients with a CYP2C9*1*3 or CYP2C9*2*3 genotype a reduced maintenance dose of 1 mg once daily is used from day 6 onwards. For dose adjustments based on lymphocyte count-consult product literature.
Cautions
Administration of vaccinations (may be less effective during siponimod treatment-consult product literature for further information); diabetes mellitus (increased risk of macular oedema); elderly (limited information available); exposure to sunlight (increased risk of cutaneous neoplasms); first- or second-degree Mobitz type I atrioventricular block; heart failure (New York Heart Association class I and II); myocardial infarction; patients receiving QT-prolonging or heart rate-lowering drugs, including beta-blockers and heart rate-lowering calcium-channel blockers (seek advice from cardiologist regarding switching to alternative drugs or appropriate monitoring); recurrent syncope; retinal disease (increased risk of macular oedema); risk of discontinuation effects, including disease rebound; severe sleep apnoea; significant QT prolongation (QTc greater than 500 milliseconds); sinus bradycardia (heart rate below 55 beats per minute); uncontrolled hypertension; uveitis (increased risk of macular oedema) Cautions, further information Bradycardia and cardiac rhythm disturbance Siponimod may cause transient bradycardia, atrioventricular conduction delays and heart block after the first dose. Siponimod is not recommended in patients with a history of symptomatic bradycardia or recurrent syncope, uncontrolled hypertension, severe untreated sleep apnoea, or significant QT prolongation unless the anticipated benefits outweigh the potential risks, and advice from a cardiologist (including monitoring advice) is sought before initiation.
Contraindications
Active malignancies; cryptococcal meningitis; decompensated heart failure (requiring inpatient treatment) in the previous 6 months; heart failure in the previous 6 months (New York Heart Association class III or IV); immunodeficiency syndrome; macular oedema; myocardial infarction in the previous 6 months; patients homozygous for CYP2C9*3*3 genotype (poor metabolisers); phototherapy with UV-B radiation or PUVA-photochemotherapy (increased risk of cutaneous neoplasms); progressive multifocal leukoencephalopathy; seconddegree Mobitz type II atrioventricular block or thirddegree AV block, or sicksinus syndrome, if the patient does not have a pacemaker; severe active infection; stroke (including transient ischaemic attack) in the previous 6 months; unstable angina pectoris in the previous 6 months
Side effects
Common or very common Arrhythmias; asthenia; atrioventricular block; diarrhoea; dizziness; headache; hypertension; increased risk of infection; lymphopenia; macular oedema; nausea; neoplasms; pain in extremity; peripheral oedema; seizure; tremor Frequency not known Meningitis cryptococcal; vision disorders
Pregnancy
Manufacturer advises avoid-toxicity in animal studies.
Breast feeding
Manufacturer advises avoid-present in milk in animal studies.
Hepatic impairment
Manufacturer advises caution when initiating treatment in mild to moderate impairment; avoid in severe impairment.
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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