Fingolimod

Mechanism :

Fingolimod-phosphate, active metabolite of fingolimod, binds to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the lymphocytes' ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the central nervous system is decreased, which reduces central inflammation.

Indication :

Multiple sclerosis

Contraindications :

Hypersensitivity to fingolimod (including rash, urticaria, and angioedema) or any component of the formulation; MI, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or New York Heart Association (NYHA) class III/IV heart failure in the past 6 months; Mobitz Type II second- or third-degree atrioventricular (AV) block or sick sinus syndrome (unless patient has a functioning pacemaker); baseline QTc interval ≥500 msec; concurrent use of a class Ia or III antiarrhythmic.

Patients at increased risk for opportunistic infections, including those who are immunocompromised due to treatment (e.g., antineoplastic, immunosuppressive or immunomodulating therapies, total lymphoid irradiation or bone marrow transplantation) or disease (e.g., immunodeficiency syndrome); severe active infections including active chronic bacterial, fungal or viral infections (e.g., hepatitis, tuberculosis); known active malignancy (excluding basal cell carcinoma); severe hepatic impairment (Child-Pugh class C)

Dosing :

Children ≥10 years and Adolescents: Oral:

≤40 kg:

0.25 mg once daily.

>40 kg:

0.5 mg once OD.

Adverse Effect :

Increased gamma-glutamyl transferase, headache, diarrhea, nausea, abdominal pain, increased serum ALT and AST, influenza, neck pain, cough, sinusitis, hypertension, first and second-degree heart block, bradycardia, seizure, migraine, alopecia, hypertriglyceridemia, lymphocytopenia, herpes virus infection.

Interaction :

Antiarrhythmic Agents (Class Ia): Fingolimod may enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia).
Antiarrhythmic Agents (Class III): Fingolimod may enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III).
Beta-Blockers: May enhance the bradycardic effect of Fingolimod.
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents.
Immunosuppressants: May enhance the immunosuppressive effect of Fingolimod.
QTc-Prolonging Agents: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QTc-Prolonging Agents.

Hepatic Dose :

Mild and moderate hepatic impairment: No dose adjustment is needed.
Severe hepatic impairment: Use is not recommended.