Drug information of Fingolimod

Fingolimod

فارسی

Treating relapsing forms of multiple sclerosis (MS) to reduce the number of flare-ups and slow down the development of physical disability associated with MS

Mechanism of effect

Metabolized to fingolimod-phosphate, which binds with a high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5, and blocks the capacity of lymphocytes to egress from lymph nodes, decreasing the number of lymphocytes in peripheral blood.

Pharmacodynamic

Fingolimod causes a transient reduction in heart rate and AV conduction at treatment initiation. Potential to prolong the QT interval. Effects on immune cell numbers in the blood-

Pharmacokinetics

Apparent absolute oral bioavailability is 93%. T max is 12 to 16 h. Food does not alter AUC or C max . More than 99.7% protein bound. Vd is approximately 1,200 L Biotransformed by 3 main pathways: reversible stereoselective phosphorylation to fingolimod-phosphate, oxidative biotransformation mainly via cytochrome P450 4F2 with subsequent fatty acid–like degradation to inactive metabolites, and formation of pharmacologically inactive nonpolar ceramide analogs. CYP2D6, 2E1, 3A4, and 4F12 have minor contributions to the metabolism of fingolimod Cl is approximately 6.3 L/h and half-life is 6 to 9 days. Approximately 81% of a dose is excreted in the urine as inactive metabolites and less than 2.5% of a dose is excreted as fingolimod and fingolimod-phosphate in the feces.

Drug indications

(multiple sclerosis (MS

Dosage

Adults PO 0.5 mg once daily.

Alerts

Monitor Observe all patients for a period of 6 h after the first dose for signs and symptoms of bradycardia. Obtain an ECG if a recent (within 6 mo) ECG is not available in patients on antiarrhythmics, those with cardiac risk factors, and those who have slow or irregular heartbeat prior to starting fingolimod. Monitor BP. Before initiating treatment, a recent CBC (within 6 mo) should be available and patients without a history of chickenpox or without vaccination against varicella zoster virus (VZV) should be tested for VZV antibodies. Monitor for infection during treatment and for at least 2 mo after discontinuing therapy. Perform an adequate ophthalmic evaluation at baseline and 3 to 4 mo after treatment initiation. If patients report visual disturbances at any time during treatment, undertake additional ophthalmologic evaluation. Patients with diabetes mellitus or a history of uveitis should have regular ophthalmologic evaluations while receiving fingolimod. Perform spirometric evaluation of respiratory function and evaluation of diffusing capacity of lungs for carbon monoxide (DL CO ) during therapy if clinically indicated. Recent (within 6 mo) transaminase and bilirubin levels should be available before initiation of treatment. Monitor liver enzymes in patients who develop symptoms suggestive of hepatic dysfunction.

Points of recommendation

Administer with or without food. Observe patients for 6 h after the first dose to monitor for signs and symptoms of bradycardia.

Drug contraindications

None well documented

Pregnancy level

C

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