etrasimod

Absorption: Unknown.

Distribution: Well distributed to extravascular tissues.

Protein Binding: 97.9%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C8, CYP2C9, and CYP3A4 isoenzymes, with some metabolism by the CYP2C19 and CYP2J2 isoenzymes. Primarily excreted in the feces (82%; 11% as unchanged drug), with 5% excreted in the urine.

Half-Life: 30 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

MI, unstable angina, stroke, transient ischemic attack, decompensated HF requiring hospitalization, or Class III or IV HF within the past 6 mo;
History or presence of Mobitz type II 2nd- or 3rd-degree heart block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker;
Active infection;
Concurrent use of moderate or strong CYP2C8 or CYP3A4 inhibitors in poor CYP2C9 metabolizers;
Severe hepatic impairment;
OB: Pregnancy.

Use Cautiously in:

QT interval prolongation (>450 msec men, >470 msec women) or concurrent use of QT interval prolonging medications;
Heart rate <50 bpm;
Cardiac arrhythmias requiring use of class Ia or III antiarrhythmics;
Ischemic heart disease, class I or II HF, cardiac arrest, cerebrovascular disease, or uncontrolled hypertension;
Symptomatic bradycardia, recurrent cardiogenic syncope, or severe untreated sleep apnea;
Mobitz type I 2nd-degree AV block, unless the patient has a functioning pacemaker;
Immunocompromised or taking other immunosuppressant medications (↑ risk of progressive multifocal leukoencephalopathy [PML]);
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, heart block, hypertension

Derm: BASAL/SQUAMOUS CELL CARCINOMA, MELANOMA

EENT: macular edema, vision abnormalities

GI: ↑liver enzymes, nausea

GU: urinary tract infection

Hemat: lymphopenia

Metab: hypercholesterolemia

MS: arthralgia

Neuro: posterior reversible encephalopathy syndrome (pres), dizziness, headache, PML

Resp: ↓pulmonary function

Misc: infection (including bacterial and viral), IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

↑risk of immunosuppression with antineoplastics, immunosuppressants, or immune modulating therapies; avoid concurrent use.
Live-attenuated vaccines↑ risk of infection; avoid concurrent use and for 5 wk following last dose.
Concurrent use of QT interval prolonging medications, class Ia antiarrhythmics, and class III antiarrhythmics may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
Moderate or strong dual CYP2C9 and CYP3A4 inhibitors, including fluconazole, may ↑ levels and risk of toxicity; concurrent use not recommended.
Rifampin may ↓ levels and effectiveness; concurrent use not recommended.

Route/Dosage ⬆ ⬇

PO (Adults ): 2 mg once daily.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Prior to initiation, obtain an ECG to determine whether pre-existing conduction abnormalities are present. Review current or prior medications to determine if patients are taking drugs that could slow HR or atrioventricular conduction. Bradycardia may develop. In patients with certain pre-existing conditions, seek advice from a cardiologist.
Monitor all patients for signs and symptoms of PRES (visual disturbances, seizure, headaches, altered mentation). If PRES occurs, permanently discontinue etrasimod.
Obtain ophthalmic assessment to get a baseline evaluation of the fundus, including the macula and visual acuity prior to treatment.
Prior to or shortly after initiation, obtain a skin examination. If suspected skin malignancy occurs, permanently discontinue etrasimod.
Monitor for signs and symptoms of infection (fever, chills, cough, headache, malaise, flu-like symptoms, dysuria, hematuria, cellulitis, erythematous nonhealing wound) during treatment and for 5 wk after discontinuation, especially with concurrent use of immunosuppressants.
Monitor for development of immune reconstitution inflammatory syndrome (lymphadenopathy, new skin lesions, shingles, retinopathy, lung symptoms) in patients who discontinue treatment in the setting of PML, which includes signs and symptoms of cognitive dysfunction, weakness, lack of coordination, gait disturbance, ataxia, hemiparesis, aphasia, hemianopia, diplopia, facial drooping, seizures, and headaches.
Monitor BP and HR at baseline and periodically during therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Obtain a recent CBC with differential within the last 6 mo or after discontinuation of prior ulcerative colitis therapy.
Obtain baseline or recent (within the last 6 mo) AST, ALT, and bilirubin levels. May ↑ AST, ALT, and bilirubin. Discontinue if liver injury develops during therapy.
Prior to initiation, test for antibodies to varicella zoster virus (VZV) in patients without health care–confirmed history of varicella (chickenpox) or without documentation of a full vaccination course against VZV.

Implementation ⬆ ⬇

Consider possible unintended additive immunosuppressive effects before initiating treatment if patients are taking antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies or if there is a history of prior use of these drugs.
PO: Administer once daily with or without food.
Prior to initiation, update immunizations in agreement with current immunization guidelines. Administration of VZV vaccination to patients who are antibody negative is recommended. If live-attenuated vaccine immunizations are required, administer ≥4 wk prior to start of therapy.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of etrasimod. Advise patient to take as directed and swallow pill whole. If a dose is missed, take the missed dose at the next scheduled time; do not double the next dose. Advise patient to read Patient Information before starting therapy.
Instruct patient to immediately report symptoms of PRES (visual changes, seizure, headaches, confusion, disorientation).
Warn patient to report symptoms of bradycardia (slow HR, skipped beats, palpitations, dizziness, light-headedness, trouble breathing, faintness).
Instruct patient to report any symptoms of infection (fever, chills, cough, headache, flu-like symptoms, urinary pain, bloody urine, vomiting, diarrhea, rash, nonhealing wound).
Advise patient to report any changes in vision or symptoms of macular edema.
Advise patient to report symptoms of liver injury (fatigue, nausea, upper abdominal pain, yellowing of eyes or skin, dark urine or stools).
Warn patient to use sunscreen, wear protective clothing, and limit exposure to sunlight and ultraviolet light due to potential for malignancies.
Counsel patient to avoid live-attenuated vaccines during and for 5 wk after treatment.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 1 wk after last dose. Inform health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes ⬆ ⬇

Achievement of clinical remission of ulcerative colitis.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-0274- Velsipity
  - 0069-0274-30- 1 BOTTLE in 1 CARTON (0069-0274-30) / 30 TABLET, FILM COATED in 1 BOTTLE

63069- Penn Pharmaceutical Services Ltd
- 63069-052-
  - 63069-052-14- 294 BLISTER PACK in 1 BOX (63069-052-14) / 14 TABLET, FILM COATED in 1 BLISTER PACK

63069- Penn Pharmaceutical Services Ltd
- 63069-052-
  - 63069-052-30- 168 BOTTLE in 1 BOX (63069-052-30) / 30 TABLET, FILM COATED in 1 BOTTLE

63539- U.S. Pharmaceuticals
- 63539-274- Velsipity
  - 63539-274-28- 28 TABLET, FILM COATED in 1 BLISTER PACK (63539-274-28)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇