伊曲莫德(Etrasimod)的注意事项和药物相互作用

Etrasimod is a sphingosine 1-phosphate (S1P) receptor modulator and needs to be used under the guidance of a physician.

Indications for Etrasimod

Ulcerative colitis

It is used to treat moderately to severely active ulcerative colitis in adults.

Precautions for Itramod (Etrasimod)

1. Infection

Itramod will reduce peripheral blood lymphocyte count, thereby increasing the risk of infection, including life-threatening infections.

Before starting treatment with itrimod, obtain a recent complete blood count and lymphocyte count (i.e., within 6 months or after discontinuation of previous treatment for ulcerative colitis). In patients with active infection, delay initiation of treatment until the infection resolves. If serious infection occurs, consider interrupting treatment with istrimod.

The effect of lowering peripheral lymphocyte counts may persist for up to 5 weeks after discontinuation of istrimod. Inform patients and healthcare providers of the ongoing risk of infection during this period.

2. Progressive multifocal leukoencephalopathy (PML)

PML has been reported in multiple sclerosis (MS) patients treated with sphingosine 1-phosphate (S1P) receptor modulators; this is associated with certain risk factors (e.g., immunocompromised patients, use of multiple immunosuppressants, longer treatment duration). Itrimod is not used to treat MS.

3. Herpes virus infection

Varicella-zoster virus meningitis and localized herpes virus infection have been reported.

For patients who do not have a history of varicella (chickenpox) diagnosis by a medical professional or who do not have complete VZV vaccination records, a VZV antibody test should be performed before starting treatment with istrimod.

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

4. Cryptococcal infection

There have been case reports of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infection.

Observe patients for clinical signs or symptoms of CM. Immediate diagnostic evaluation and treatment are recommended for patients who develop signs or symptoms of cryptococcal infection; discontinue istrimod until the diagnosis of cryptococcal infection has been ruled out. If CM is diagnosed, appropriate treatment should be initiated.

Prior and concurrent use of antineoplastic, immunomodulatory, or noncorticosteroid immunosuppressive therapy

Concomitant use of itrimod with antineoplastic, immunomodulatory, or noncorticosteroid immunosuppressive therapy has not been studied.

Due to the risk of additive immunosuppression, avoid concurrent use of these drugs during treatment with istrimod and for several weeks after discontinuation.

5. Vaccination

For patients who do not have a history of varicella (chickenpox) diagnosis by a medical professional or who do not have complete VZV vaccination records, a VZV antibody test should be performed before starting treatment with istrimod. For antibody-negative patients, it is recommended to complete the full course of VZV vaccination before starting isramod treatment; delay starting isramod treatment for 4 weeks after vaccination to allow the vaccine to fully exert its effect.

There are no clinical data on the safety and effectiveness of vaccination during treatment with itrimod; efficacy may be reduced when vaccination is given during treatment with itramod.

If a live attenuated vaccine is required, it should be given at least 4 weeks before starting treatment with istrimod. Avoid use of live-attenuated vaccines during treatment and for 5 weeks after stopping itrimod.

Update immunizations according to current immunization guidelines before initiating treatment with istrimod.

6. Bradycardia and atrioventricular conduction delay

Starting the use of istrimod will cause a transient decrease in heart rate and atrioventricular conduction.

If treatment with istrimod is considered, cardiologist opinion should be sought in individuals with: significant QT prolongation (QTcF ≥ 450 msec in men, ≥ 470 msec in women); arrhythmias requiring treatment with Class Ia or Class III antiarrhythmic drugs or QT prolonging drugs.

Unstable ischemic heart disease, grade I or II HF, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension; resting heart rate <50 beats/minute; history of symptomatic bradycardia, recurrent cardiogenic syncope, or severe untreated sleep apnea; or history of Mohs type I second-degree AV block (unless the patient has a functional pacemaker implanted).

7. Liver damage

Elevated transaminases may occur.

If recent data are not available (i.e., within the past 6 months), obtain transaminase and bilirubin levels before initiating treatment with istrimod.

Transaminase and bilirubin levels should also be obtained in patients who develop symptoms suggestive of hepatic insufficiency (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark-colored urine). If significant hepatic injury is confirmed, discontinue itrimod.

8. Macular edema

Increases the risk of macular edema.

Obtain a baseline fundus evaluation, including macular examination, shortly after initiating itrimod therapy. Perform fundus evaluations (including macular examination) regularly during treatment and anytime if any changes in vision occur. If macular edema occurs, consider discontinuing itrimod.

9. Increased blood pressure

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) may increase. Monitor blood pressure during treatment with istrimod and perform appropriate management.

10. Fetal/neonatal morbidity and mortality

Based on animal data, administration during pregnancy may cause harm to the fetus. Embryo-fetal toxicity has been demonstrated in animals.

Inform pregnant women and women of childbearing potential of the potential risks to the fetus. It is recommended that females of childbearing potential use effective contraception during treatment with istrimod and for 1 week after the last dose.

11. Cutaneous malignant tumors

Patients treated with S1P receptor modulators have an increased risk of developing cutaneous malignant tumors (including basal cell carcinoma, squamous cell carcinoma, and melanoma).

Skin examinations are recommended before or shortly after starting treatment with istrimod and regularly thereafter, especially in patients with risk factors for skin cancer. Monitor for suspicious skin lesions; if detected, evaluate promptly.

Limit sun and UV exposure by wearing protective clothing and using high protection factor sunscreen. The use of UV-B phototherapy or psoralen plus ultraviolet A (PUVA) photochemotherapy during treatment with istrimod is not recommended.

12. Posterior Reversible Encephalopathy Syndrome (PRES)

If a patient develops any neurological or psychiatric signs or symptoms (e.g., cognitive deficits, behavioral changes, cortical visual impairment, or any other neurocortical signs/signs), or any signs or symptoms suggestive of increased intracranial pressure or accelerated deterioration of neurological function, a comprehensive physical and neurological examination should be scheduled immediately, and an MRI examination should be considered.

If PRES is suspected, discontinue istrimod.

13. Respiratory system effects

Some patients have reported a decrease in the absolute value of forced expiratory volume in one second (FEV1) as early as 3 months after the start of treatment. It is unclear whether the decrease in FEV1 is reversible after discontinuation of the drug.

Perform spirometry assessment of respiratory function during treatment with istrimod if clinically indicated.

14. Additive immunosuppressive effects

When switching from drugs with long-acting immunosuppressive effects to itridimod, the half-life and mechanism of action of these drugs should be considered to avoid unexpected additive immunosuppressive effects.

Itramod (Etrasimod) drug interactions

1. Drugs that affect liver microsomal enzymes

The effect of simultaneous use of Etrasimod in combination with drugs that have moderate to strong inhibitory or inducing effects on CYP2C8, CYP2C9, or CYP3A4 is unknown. However, clinically important changes in exposure cannot be excluded when ≥2 metabolic pathways are affected.

2. Moderate to strong inhibitor of CYP2C9 and CYP3A4

Coadministration of moderate to strong inhibitors of CYP2C9 and CYP3A4: May increase itrimod exposure.

It is not recommended to use them at the same time.

3. CYP2C9 poor metabolizers who use CYP2C8 or CYP3A4 inhibitors

Among CYP2C9 poor metabolizers, concurrent use of moderate or strong inhibitors of CYP2C8 or CYP3A4 is expected to increase the exposure of itridimod, and simultaneous use is not recommended.