etrasimod

Action and Spectrum

Actions and Spectrum: 

etrasimod (Velsipity), which is a selective sphingosine 1-phosphate receptor modulator, developed as a treatment for inflammatory bowel disease (IBD) and other autoimmune conditions. 

etrasimod binds and activates S1P receptors in the body, which are located on various immune cells, including lymphocytes. By activating these receptors, etrasimod can prevent the lymphocytes from leaving lymph nodes and entering the bloodstream, where they could migrate to areas of inflammation and exacerbate autoimmune disease symptoms. 

In other words, etrasimod acts as an immunomodulatory agent by preventing the migration of immune cells from lymphoid tissues to sites of inflammation. This is thought to reduce inflammation in affected tissues and improve disease symptoms. 

etrasimod (Velsipity) has a high affinity for the S1P1 receptor subtype, mainly responsible for regulating lymphocyte migration. By selectively targeting this receptor subtype, etrasimod can achieve its therapeutic effects while minimizing the potential for off-target effects on other S1P receptor subtypes, which are involved in other physiological processes such as vascular tone and cardiac function. 

Overall, etrasimod has a broad spectrum of action in treating autoimmune diseases, including IBD, multiple sclerosis, and psoriasis. 

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

Elevated liver tests (5-6%)

Arthralgia (4%)

Dizziness (5%)

Nausea (3-4%)

Urinary tract infection (3%)

Headache (6-9%)

Hypertension (3%)

Hypercholesterolemia (3%)

Bradycardia (3%)

Decrease in visual acuity (2.6%)

Herpes viral infection (2%)

Black Box Warning

Black Box Warning: 

etrasimod has a black box warning regarding the risk of serious infections. It is intended to highlight severe or life-threatening risks associated with a medication. 

etrasimod can increase the risk of serious infections, including opportunistic infections such as herpes zoster, tuberculosis, and invasive fungal infections.

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

There are several contraindications for the use of etrasimod: 

• Hypersensitivity: etrasimod is contraindicated in patients with a known hypersensitivity to the active ingredient or any of the excipients in the formulation. 
• Severe liver impairment: etrasimod is metabolized by the liver, and patients with severe liver impairment may be unable to process the medication effectively. Therefore, etrasimod is contraindicated in patients with severe hepatic impairment. 
• Concomitant use of CYP2C9 and CYP3A4 inhibitors: etrasimod is metabolized by CYP2C9 and CYP3A4 enzymes in the liver. Concomitant use of drugs that inhibit these enzymes can increase exposure to etrasimod and increase the risk of adverse effects. Therefore, etrasimod is contraindicated in patients receiving strong inhibitors of CYP2C9 and CYP3A4, such as ketoconazole and clarithromycin. 
• Active systemic infections: etrasimod increases the risk of serious infections, including opportunistic infections such as herpes zoster, tuberculosis, and invasive fungal infections. Therefore, etrasimod is contraindicated in patients with active systemic infections. 
• Pregnancy: etrasimod may cause fetal harm if used during pregnancy. Therefore, etrasimod is contraindicated in pregnant women. 

Caution 

There are several cautions to consider when using etrasimod: 

• Cardiac effects: etrasimod may cause bradycardia (slow heart rate), especially when first starting treatment or after a missed dose. Patients should be monitored for changes in pulse rate and rhythm, and etrasimod should be used cautiously in patients with pre-existing heart conditions or conduction abnormalities. 
• Macular edema: etrasimod may cause macular edema, which can lead to vision changes. Patients should have a baseline eye exam before starting treatment and should be monitored for vision changes during treatment. etrasimod should be used with caution in patients with a history of macular edema or uveitis. 
• Hepatic effects: etrasimod may cause elevations in liver enzymes. Patients should have baseline liver function tests before starting treatment and be monitored for liver function during treatment. etrasimod should be used cautiously in patients with mild to moderate hepatic impairment. 
• Immunosuppression: etrasimod can increase the risk of serious infections, including opportunistic infections such as herpes zoster, tuberculosis, and invasive fungal infections. Patients should be screened for the latent tuberculosis infection before starting treatment and monitored for signs and symptoms of infection during treatment. etrasimod should be used with caution in immunocompromised patients or taking immunosuppressive medications. 
• Drug interactions: etrasimod is metabolized by CYP2C9 and CYP3A4 enzymes in the liver. Concomitant use of drugs that induce or inhibit these enzymes can affect the metabolism of etrasimod and may require dosage adjustments. Patients should inform their healthcare provider about their medications before starting treatment with etrasimod. 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

etrasimod is a sphingosine 1-phosphate receptor modulator that selectively binds to sphingosine 1-phosphate receptor 1 and 5 subtypes. By binding to these receptors, etrasimod inhibits the egress of lymphocytes from lymphoid tissues, reducing the number of circulating immune cells in the blood. 

Pharmacodynamics: 

Mechanism of action: The medication acts as a sphingosine 1-phosphate (S1P) receptor one modulator, specifically binding with high affinity to S1P receptors 1, 4, and 5. By doing so, it blocks the capacity of lymphocytes to regress from lymph nodes, which reduces the number of lymphocytes in peripheral blood and decreases inflammation. This effect helps to reduce the frequency of relapses in certain autoimmune diseases, including multiple sclerosis. 

Pharmacokinetics: 

Absorption 

etrasimod is well-absorbed after oral administration, with peak plasma concentrations reached within 2 to 3 hours after dosing. The absolute bioavailability of etrasimod has yet to be established, but the drug is known to have high oral bioavailability. 

Distribution 

etrasimod is widely distributed in the body, with a volume of distribution of approximately 350 L. The drug is highly protein-bound (more than 99%), primarily to albumin, and it is not known whether etrasimod crosses the blood-brain barrier. 

Metabolism 

etrasimod is extensively metabolized in the liver by cytochrome P450 (CYP) enzymes, primarily CYP2C9 and CYP3A4, to form several metabolites. The major metabolite, M3, is approximately ten times less potent than the parent drug in vitro. M4, another metabolite, is approximately equipotent to etrasimod in vitro. The metabolites of etrasimod are excreted primarily in the feces. 

Elimination and Excretion 

etrasimod and its metabolites are eliminated primarily in the feces, with less than 1% of the dose excreted in the urine. The elimination half-life of etrasimod is approximately 30 hours. Steady-state concentrations are achieved after 7 to 10 days of once-daily dosing. 

Adminstartion

Administration: 

Oral administration 

etrasimod (Velsipity) is available in oral tablets and should be taken once daily, with or without food. The recommended dose for most indications is 2 mg per day. etrasimod should be generally taken at the same time each day to maintain a consistent level of medication in the body. 

The dose and duration of etrasimod treatment may vary depending on the patient’s condition and response to therapy. Follow the instructions provided by physician regarding how to take etrasimod. 

If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.

Patient Information Leaflet

Patient information leaflet 

Generic Name: etrasimod 

Why do we use etrasimod? 

etrasimod (Velsipity) is approved for treating moderate-to-severe active ulcerative colitis in adult patients. etrasimod works by selectively binding to sphingosine 1-phosphate receptors in the body, which can reduce inflammation and prevent immune cells from migrating to sites of inflammation. This mechanism of action is thought to be beneficial in treating inflammatory bowel disease and multiple sclerosis. 

It is also used for treating moderate-to-severe Crohn’s disease in elder patients who have not responded adequately to other therapies. It is currently being investigated for treating relapsing multiple sclerosis. 

Patients should discuss the potential risks and benefits of etrasimod with their healthcare provider before starting treatment. They should also report any new or unusual symptoms to their healthcare provider during treatment.