What Is Fingolimod?

Fingolimod, alias Fingolid, is a chemical. The chemical name is 2-amino-2- [2- (4-octylphenyl) ethyl] -1,3-propanediol, the molecular formula is C ₁₉ H ₃₃ NO ₂ , and the molecular weight is 307.47100. Fingolimod is a receptor modulator and is mainly used clinically to treat relapsing-remitting multiple sclerosis.

Chinese name: Fingolimod
Foreign name: Fingolimod

CAS number: 162359-55-9
Molecular formula: C19H33NO2

Fingolimod Compound Introduction

Fingolimod Basic Information

Chinese name: 2-amino-2- [2- (4-octylphenyl) ethyl] -1,3-propanediol

English name: fingolimod

English alias: 2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol; Fingolimod; UNII-3QN8BYN5QF;

CAS number: 162359-55-9

Molecular formula: C ₁₉ H ₃₃ NO ₂

Chemical structure:

Molecular weight: 307.47100

Exact mass: 307.25100

PSA: 66.48000

LogP: 3.90460 ^[1]

Fingolimod Properties

Density: 1.016g / cm ³

Boiling point: 479.5ºC at 760 mmHg

Flash point: 243.8ºC ^[1]

Fingolimod drug-related information at a glance

Fingolimod is the first sphingosine 1-phosphate receptor modulator to prevent lymphocytes from leaving the lymph nodes, reducing the frequency of disease recurrence in patients with multiple sclerosis and delaying the deterioration of patients with multiple sclerosis. It can also maintain specific immune cells in the lymph nodes, prevent them from acting on the central nervous system and cause damage, and the retentivity of lymphocytes is reversible, so that the lymphocytes circulating in the body return to normal levels after the treatment is stopped ^{[ 2]} .

Fingolimod drug name

Chinese name fingomod

Chinese alias: Fingolid

English alias: fingolimod ^[2]

Fingolimod dosage forms and specifications

0.5 mg hard capsule.

Fingolimod pharmacological action

There are two main mechanisms of action:

One is to encourage lymphocytes to migrate back to the lymph nodes (away from the central nervous system),

The second is to regulate the S1P receptor of nerve cells. ^[2]

Fingolimod Indications and Uses

Fingolimod is a sphingosine 1-phosphate receptor modulator suitable for the treatment of patients with relapsing multiple sclerosis, reducing the frequency of clinical exacerbations and delaying the accumulation of physical disabilities. ^[2]

Fingolimod dosage and method of administration

(1) The recommended dose of fingolimod is 0.5 mg orally once daily. A dose higher than 0.5 mg fingolimod was associated with a higher incidence of adverse reactions without increasing benefit. Fingolimod can be taken with or without food.

(2) First dose monitoring:

1) Observe the signs and symptoms of bradycardia in all patients for at least 6 hours after the first dose, and measure the pulse and blood pressure every hour. ECG was obtained before dosing and at the end of the observation period.

2) Patients with a heart rate of <45 bpm, or new onset of second-degree or higher atrioventricular block should be monitored until resolution is found. Patients with the lowest heart rate at the end of the observation period after dosing should be monitored until the heart rate increases.

3) In patients with symptomatic bradycardia, start continuous ECG monitoring until the symptoms have been resolved; if pharmacological intervention is required to treat bradycardia, continuous ECG monitoring should be continued overnight in a medical device and the second dose The first dose monitoring method should be repeated.

4) Patients who are at high risk of symptomatic bradycardia or cardiac block because of a coexisting medical condition or some concurrent medication should be monitored with continuous ECG overnight

5) Patients who prolong the QTc interval at baseline or during the observation period, or take drugs with a known risk of torsional ventricular tachycardia should be monitored overnight with continuous ECG monitoring ^[2] .

Fingolimod contraindications

(1) Recently (within the past 6 months): myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or class III / IV heart failure

(2) Presence or history of Mobitz's type II second- or third-degree AV block or sick sinus syndrome, unless the patient has a pacemaker.

(3) Baseline QTc interval 500 ms

(4) Treatment with class Ia or class III antiarrhythmic drugs ^[2] .

Fingolimod notes

(1) Slow heart rate and / or atrioventricular conduction after first dose of fingolimod: monitor patients

(2) Infection: Fingolimod may increase the risk of infection. A recent complete blood count CBC should be obtained before starting treatment with fingolimod. Monitor for signs and symptoms of infection during treatment and for 2 months after termination. Do not start fingolimod therapy in patients with active acute or chronic infections.

(3) Macular edema: vision symptoms may or may not occur. An ophthalmological evaluation should be performed before starting fingolimod and after 3-4 months after the start of treatment. Vision is monitored at baseline and during routine evaluations of patients. Patients with diabetes or a history of uveitis increase the risk and should have routine eye evaluation.

(4) Fingolimod reduced lung function test: When clinically indicated, vital capacity and lung diffusion carbon monoxide were obtained.

(5) Liver effect: Fingolimod may increase liver transaminase. Recent liver enzyme results should be obtained before starting fingolimod. Assess liver enzymes if liver damage is suspected. Terminate fingolimod if significant liver damage occurs.

(6) Fetal risk: Women with childbearing ability should use effective contraceptives when using fingolimod and 2 months after discontinuation ^[2] .

Fingolimod adverse reactions

The most common adverse reactions (incidence 10% and> placebo): headache, flu, diarrhea, back pain, elevated liver transaminase, and cough.

Fingolimod drug interactions

(1) Ketoconazole: Because fingolimod exposure is increased by 70% and the risk of adverse reactions is greater when ketoconazole is used systemically, patients are closely monitored.

(2) Vaccines: Avoid or attenuate vaccines during fingolimod treatment and 2 months after discontinuation due to the risk of infection ^[2] .

Fingolimod Special Populations

(1) Pregnancy: According to animal data, it may cause fetal harm. Pregnancy registration is available.

(2) Pediatric patients: safety and effectiveness have not been determined.

(3) Liver impairment: Closely monitor patients with severe liver impairment, double the exposure due to fingolimod, and a greater risk of adverse reactions ^[2] .

Fingolimod adverse reactions

The most frequent adverse reactions (incidence 10% and> placebo) to fingolimod 0.5 mg were headache, flu, diarrhea, back pain, elevated liver enzymes, and cough. The only adverse event that caused treatment discontinuation was reported at a rate of> 1%. Fingolimod 0.5 mg was an increase in serum aminotransferase (3.8%) ^[2] .

Fingolimod overdose

No cases of overdose have been reported. However, single doses up to 80-fold the recommended dose (0.5 mg) resulted in no clinically significant adverse effects. At 40 mg, 5/6 subjects reported mild chest urgency or discomfort which was consistent with a clinically small airway response.
Neither dialysis nor plasma exchange can result in the removal of fingolimod from the body ^[2] .

Fingolimod Pharmacokinetics

The peak time Tmax of fingolimod is 12-16 hours. Apparent absolute oral bioavailability is 93%, and food intake does not change the Cmax or exposure (AUC) of fingolimod or fingolimod-phosphate. So you can take fingolimod without considering meals.

Steady-state blood concentrations and steady-state levels within about 1 to 2 months after dosing once a day are about 10-fold greater than the initial dose.

Fingolimod is highly distributed (86%) within red blood cells. Fingolimod-phosphate has a smaller <17% uptake in blood cells. Fingolimod and fingolimod-phosphate are> 99.7% protein bound. Kidney or liver damage does not alter the protein binding of fingolimod and fingolimod-phosphate ^[2] .