VELSIPITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VELSIPITY (VELSIPITY).
Sphingosine 1-phosphate (S1P) receptor modulator; selectively binds to S1P receptor subtypes 1, 4, and 5, inhibiting lymphocyte egress from lymphoid tissues, thereby reducing circulating lymphocytes.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C8; undergoes oxidation and glucuronidation. |
| Excretion | Primarily eliminated via biliary/fecal route (approximately 70% as unchanged drug) and renal excretion (approximately 30% as unchanged drug and metabolites, with less than 1% as unchanged drug in urine). |
| Half-life | Terminal elimination half-life is approximately 20 days. This long half-life allows for weekly oral dosing and requires a prolonged washout period before initiating other treatments. |
| Protein binding | >99% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution is approximately 3000 L (or ~43 L/kg assuming 70 kg body weight), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 70%. |
| Onset of Action | Following oral administration, reduction in absolute lymphocyte count (ALC) occurs within 4 hours, with maximum reduction achieved by 2-4 weeks. |
| Duration of Action | Duration of action is approximately 1-2 weeks after a single dose, based on sustained lymphocyte suppression. After discontinuation, ALC recovers to normal range within 4-6 weeks in most patients. |
| Molecular Weight | 462.6 |
0.23 mg subcutaneously once weekly.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Not recommended in end-stage renal disease (GFR <15 mL/min) unless on stable dialysis. |
| Liver impairment | No dose adjustment for mild or moderate hepatic impairment (Child-Pugh A or B). Not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment. Use with caution due to age-related comorbidities and increased infection risk. |
| 1st trimester | No data in pregnant women; animal studies show reproductive toxicity. Avoid use unless no safer alternative. |
| 2nd trimester | No data in pregnant women; animal studies show fetal harm. Avoid use unless clearly needed. |
| 3rd trimester | No data in pregnant women; potential for adverse effects on newborn. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for VELSIPITY (VELSIPITY).
| Placental transfer | Likely crosses placenta due to molecular weight <500 Da; no human data. |
| Breastfeeding | It is not known whether VELSIPITY is excreted in human milk. Because of potential serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for 2 weeks after the last dose. |
■ FDA Black Box Warning
Increased risk of serious infections, including opportunistic infections such as cryptococcal meningitis and progressive multifocal leukoencephalopathy (PML). Also associated with severe hepatic injury and fetal risk.
| Serious Effects |
Hypersensitivity to etrasimod or any excipientCurrent or recent (within 6 months) myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or New York Heart Association (NYHA) class III/IV heart failurePresence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block, unless patient has a functioning pacemakerSevere untreated sleep apneaConcurrent use of a monoamine oxidase inhibitor (MAOI) or within 21 days of MAOI discontinuation
| Precautions | Infections: Increased risk of serious and opportunistic infections; screen for active infections before initiation., Hepatic injury: Can cause elevated liver enzymes and severe hepatic injury; monitor liver function., Fetal risk: May cause fetal harm; advise effective contraception., Cardiovascular effects: May cause transient decreases in heart rate and AV conduction delays; monitor at initiation., Posterior reversible encephalopathy syndrome (PRES): Cases reported; evaluate if symptoms occur., Cutaneous malignancies: Increased risk of basal cell carcinoma; monitor for skin lesions., Macular edema: Can cause macular edema; perform ophthalmologic evaluation before and during treatment. |
Loading safety data…
| Lactation Rating |
| L5 |
| Teratogenic Risk | VELSIPITY (etrasimod) is a sphingosine 1-phosphate receptor modulator. Based on animal studies, there is evidence of fetal harm including increased embryofetal mortality, skeletal abnormalities, and decreased fetal weight at maternal exposures below the clinical dose. In humans, no adequate studies exist. Use during pregnancy is contraindicated unless the benefit clearly outweighs the risk. Women of childbearing potential should use effective contraception during treatment and for 1 week after discontinuation. |
| Fetal Monitoring | Monitor for bradycardia and atrioventricular block during treatment initiation, especially in patients with preexisting cardiac conditions. Assess liver function tests periodically. Monitor for infections including opportunistic infections. For pregnant women, fetal ultrasound to assess for anomalies may be considered given animal findings. |
| Fertility Effects | In animal studies, no adverse effects on male or female fertility were observed at clinically relevant exposures. However, in humans, effects on fertility have not been studied. Due to the prolonged half-life and immunomodulatory effects, potential for impaired fertility cannot be excluded. |
| Food/Dietary | Avoid grapefruit and grapefruit juice. No other food interactions known. |
| Clinical Pearls | VELSIPITY (etrasimod) is a sphingosine 1-phosphate receptor modulator indicated for moderately to severely active ulcerative colitis. Monitor for bradycardia at treatment initiation; consider ECG if pre-existing cardiac conditions. Assess liver function tests before and during therapy due to potential transaminase elevations. Avoid concurrent use with strong CYP3A4 inducers or inhibitors. Vaccinate against varicella zoster virus if seronegative prior to starting treatment. |
| Patient Advice | Take exactly as prescribed; do not change dose or stop without consulting your doctor. · Report any symptoms of slow heart rate (dizziness, fainting, chest discomfort) especially after the first dose. · Notify your doctor immediately if you experience jaundice, dark urine, or upper right abdominal pain (signs of liver problems). · Avoid grapefruit and grapefruit juice during treatment as they can increase drug levels. · Inform your doctor before receiving any vaccines; live vaccines are not recommended during therapy. |