Pronunciation: fin-GOL-i-mod HYE-droe-KLOR-ide
- Capsules 0.5 mg
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.
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.
Special PopulationsRenal Function Impairment
Fingolimod C max and AUC are increased by 32% and 43%, respectively, and by 25% and 14%, respectively, for fingolimod-phosphate in patients with severe renal impairment. Elimination half-life did not change. Not studied in patients with mild or moderate renal impairment.Hepatic Function Impairment
No change in fingolimod C max was observed, but AUC increased by 12%, 44%, and 103% in patients with mild, moderate, or severe hepatic impairment, respectively, and half-life was prolonged by approximately 50% in patients with moderate or severe hepatic impairment. Fingolimod-phosphate C max was decreased by 22% and AUC was not substantially changed in patients with severe hepatic impairment.Elderly
Results from population pharmacokinetics suggest that dosage adjustment would not be necessary in elderly patients.Gender
No clinically significant influence on fingolimod and fingolimod-phosphate pharmacokinetics.Race
Effects of race on fingolimod and fingolimod-phosphate pharmacokinetics cannot be adequately assessed because of the low number of nonwhite patients in the clinical program.
Indications and Usage
Treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
None well documented.
Dosage and AdministrationAdults
PO 0.5 mg once daily.
- Administer with or without food.
- Observe patients for 6 h after the first dose to monitor for signs and symptoms of bradycardia.
Store between 59° and 85°F. Protect from moisture.
Drug InteractionsAntineoplastics, immune modulating therapies, immunosuppressive agents
Concurrent use with fingolimod may increase the risk of immunosuppression and infection. Use caution when switching patients from long-acting therapies with immune effects (eg, mitoxantrone, natalizumab).Beta-blockers (eg, atenolol), diltiazem
The heart rate–lowering effects may be increased. Carefully monitor patients during initiation of therapy.Class Ia (eg, procainamide, quinidine) and class III (eg, amiodarone, sotalol) antiarrhythmic agents
Class Ia and class III antiarrhythmic agents have been associated with torsades de pointes in patients with bradycardia. Because initiation of fingolimod treatment results in decreased heart rate, patients receiving class Ia or class III antiarrhythmics should be closely monitored.Ketoconazole
Fingolimod and fingolimod-phosphate blood concentrations are increased 1.7-fold when ketoconazole is given concomitantly. The risk of adverse reactions may be increased. Closely monitor the clinical response.Vaccines
Vaccination may be less effective during and for up to 2 months after discontinuing fingolimod. Live attenuated vaccine administration should be avoided during this period.
Laboratory Test Interactions
Because fingolimod reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be used to evaluate the lymphocyte subset status. A recent CBC should be available before starting fingolimod treatment.
Hypertension (6%); bradycardia (4%).
Headache (25%); depression (8%); dizziness (7%); migraine, paresthesia (5%); asthenia (3%).
Alopecia (4%); eczema, pruritus (3%).
Vision blurred (4%); eye pain (3%).
Diarrhea (12%); gastroenteritis (5%).
Lymphopenia (4%); leukopenia (3%).
ALT/AST increased (14%); GGT increased (5%); blood triglycerides increased (3%).
Weight decreased (5%).
Back pain (12%).
Cough (10%); bronchitis, dyspnea (8%); sinusitis (7%).
Influenza viral infections (13%); herpes viral infections (9%); tinea infections (4%).
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.
Category C .
Safety and efficacy in children younger than 18 y of age have not been established.
Use with caution, reflecting the greater frequency of decreased hepatic or renal function, and of concomitant disease or other drug therapy.
The blood level of some metabolites is increased in patients with severe renal impairment. Toxicity of these metabolites has not been fully explored.
Closely monitor patients with severe hepatic impairment because the risk of adverse reactions may be greater. Risk of elevated liver enzymes may be increased in patients with preexisting liver disease.
AV conduction delays have occurred after initiation of treatment. These reactions are usually transient and asymptomatic, resolving in the first 24 h on treatment, but have occasionally required treatment.
Elevations in BP may occur after approximately 2 mo of treatment and may persist with continued treatment.
A decrease in heart rate may occur, especially after the first dose.
If discontinued for more than 2 wk, the effects on heart rate and AV conduction may recur with reintroduction of fingolimod; apply the same precautions used for initial dosing.
Elevations of liver enzymes may occur.
May increase the risk for infections, some serious, because of a reduction in peripheral lymphocyte count to 20% to 30% of baseline values. Consider suspending treatment if a patient develops a serious infection.
May occur. The risk may be increased in patients with diabetes mellitus or a history of uveitis.
Dose-dependent reductions in forced expiratory volume at 1 second and DL CO may be observed as early as 1 mo after treatment initiation.
Varicella zoster virus
Consider VZV vaccination for antibody-negative patients prior to initiating treatment with fingolimod. Postpone treatment for 1 mo to allow full effect of vaccination to occur.
Mild chest tightness or discomfort consistent with small airway reactivity.
- Encourage patients to read the Medication Guide before starting therapy and with each refill.
- Inform patients of the benefits and potential risks of treatment with fingolimod. Instruct patients to take once daily as prescribed. Advise patients not to discontinue treatment without first discussing it with the prescribing health care provider.
- Advise patients that initiation of treatment results in a transient decrease in heart rate. Inform patients that they will need to be observed in the health care provider's office or other facility for 6 h after the first dose. Advise patients that if drug is discontinued for more than 2 wk, effects similar to those observed with the first dose may occur and observation for 6 h will be needed on treatment reinitiation.
- Inform patients that they may be more likely to get infections when taking fingolimod, and that they should contact their health care provider if they develop symptoms of infection. Advise patients that use of some vaccines should be avoided during treatment and for 2 months after discontinuation. Advise patients who have not had chickenpox or vaccination to consider VZV vaccination prior to initiating treatment with fingolimod.
- Advise patients that drug may cause macular edema, and that they should contact their health care provider if they experience any changes in vision. Inform patients with diabetes mellitus or a history of uveitis that their risk for macular edema is increased.
- Advise patients that they should contact their health care provider if they experience new onset or worsening of dyspnea.
- Inform patients that drug may increase liver enzymes. Advise patients that they should contact their health care provider if they have unexplained abdominal pain, anorexia, dark urine, fatigue, jaundice, nausea, and/or vomiting.
- Advise women of childbearing age of the need for effective contraception during treatment and for 2 mo after discontinuation.
- Advise patients that drug remains in the blood and continues to have effects, including decreased blood lymphocyte counts, for up to 2 mo following the last dose.
Copyright © 2009 Wolters Kluwer Health.