Drug reference

siponimod

Sphingosine-1-phosphate (S1P) receptor modulator (selective S1P1/S1P5) · Immunomodulator

START

5-day titration (0.25→2 mg) then 2 mg PO daily; ECG/MO baseline

TYPICAL MAX

2 mg/day (1 mg/day for CYP2C9*1/*3 or *2/*3)

STOP IF

PML signs, severe bradycardia/AV block, or hepatotoxicity

WATCH

ECG first-dose, OCT (macular oedema), CBC, LFTs, varicella IgG

CDSCO approvedATC L04AA42

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · absorption
PEAK: 4h · Tmax
t½: 1.3d · t½
DURATION: 1d · once-daily

EXCRETION

Mainly faecal; minor renal

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Contraindicated — fetal harm; effective contraception during and 10 days after.

FDA category + note

Top interactionssee all 12 →

Cyp2c93ContraindicatedDatabaseKimi deep-research + Cla
AbarelixSevereDatabaseDDInter
AbataceptSevereDatabaseDDInter
AbemaciclibSevereDatabaseDDInter

Mechanism

Selective modulator of S1P1 (lymphocyte egress) and S1P5 (oligodendrocyte) receptors, causing lymphocyte sequestration in lymphoid tissue and modulating CNS oligodendrocyte function — disease-modifying effect in active secondary progressive MS.

Indications

Active secondary progressive multiple sclerosis (relapsing forms)

Dosing

Adult: Titrate: 0.25 mg day 1, 0.25 mg day 2, 0.5 mg day 3, 0.75 mg day 4, 1.25 mg day 5, then 2 mg PO once daily (CYP2C9*1/*1 or *1/*2). CYP2C9*1/*3 or *2/*3: maintenance 1 mg/day. *3/*3: contraindicated.
Pediatric: Not established.
Renal adjustment: No dose adjustment.
Hepatic adjustment: No specific adjustment; not studied in severe.
Geriatric: Limited data.
Max dose: 2 mg/day (1 mg/day in CYP2C9*1/*3 or *2/*3)

Pharmacokinetics

Onset

Lymphocyte sequestration within hours of first dose

Peak effect

~4 h (Tmax)

Duration

~24 h (once-daily)

Half-life

~30 h

Bioavailability

~84% (food does not affect)

Protein binding

>99.9%

Metabolism

CYP2C9 (primary) and CYP3A4

Excretion

Mainly faecal; minor renal

Contraindications

CYP2C9*3/*3 genotype (markedly increased exposure)
Recent (≤6 months) myocardial infarction / unstable angina / stroke / decompensated heart failure
Mobitz II second-/third-degree AV block, sick sinus syndrome without pacemaker, baseline QTc ≥500 ms
Severe active infection / active malignancy

Side effects

Common

HeadacheHypertensionTransaminase elevationBradycardia (first-dose)LymphopeniaMacular oedema

Serious

First-dose bradycardia / heart block
Macular oedema
Progressive multifocal leukoencephalopathy
Serious infections (varicella, herpes)
Hepatotoxicity
Severe rebound MS activity on discontinuation

Pregnancy & lactation

Pregnancy

Contraindicated — fetal harm; effective contraception during and 10 days after.

Lactation

Avoid breastfeeding during therapy.

Drug interactions

Cyp2c93

Contraindicated

Database

Markedly increased exposure

Contraindicated per genotype testing

Source: Kimi deep-research + Cla

Abarelix

Severe

Database