FINGOLIMOD- fingolimod hydrochloride capsule
Apotex Corp.



Fingolimod Capsules are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in patients 10 years of age and older.


Cardiac Evaluation

Obtain a cardiac evaluation in patients with certain preexisting conditions [see Warnings and Precautions ( 5.1)].

Prior to starting treatment, determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction [see Dosage and Administration (2.4), Drug Interactions (7.5)].

Complete Blood Count (CBC)

Review results of a recent CBC [see Warnings and Precautions (5.2), Drug Interactions (7.6)].

Serum Transaminases (ALT and AST) and Total Bilirubin Levels
Prior to starting treatment with Fingolimod Capsules (i.e., within 6 months), obtain serum transaminases [alanine transaminase (ALT) and aspartate transferase (AST)] and total bilirubin levels [see Warnings and Precautions (5.5)].

Prior Medications

If patients are taking antineoplastic, immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with Fingolimod Capsules [see Warnings and Precautions (5.2), Drug Interactions (7.4)].


Test patients for antibodies to varicella zoster virus (VZV) before initiating Fingolimod Capsules; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with Fingolimod Capsules [see Warnings and Precautions (5.2)]. It is recommended that pediatric patients if possible, complete all immunizations in accordance with current immunization guidelines prior to initiating Fingolimod Capsules therapy.

2.2 Important Administration Instructions

Patients who initiate Fingolimod Capsules, and those who reinitiate treatment after discontinuation for longer than 14 days, require first-dose monitoring. This monitoring is also recommended when the dose is increased in pediatric patients [see Dosage and Administration (2.4, 2.5)].

Fingolimod Capsules can be taken with or without food.

2.3 Recommended Dosage

In adults and pediatric patients 10 years of age and older weighing more than 40 kg, the recommended dosage of Fingolimod Capsules is 0.5 mg orally once-daily.

Fingolimod doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefit.

2.4 First-Dose Monitoring

Initiation of Fingolimod Capsules treatment results in a decrease in heart rate, for which monitoring is recommended [see Warnings and Precautions ( 5.1), Clinical Pharmacology ( 12.2)]. Prior to dosing and at the end of the observation period, obtain an electrocardiogram (ECG) in all patients.

First 6-Hour Monitoring

Administer the first dose of Fingolimod Capsules in a setting in which resources to appropriately manage symptomatic bradycardia are available. Monitor all patients for 6 hours after the first dose for signs and symptoms of bradycardia with hourly pulse and blood pressure measurement.

Additional Monitoring After 6-Hour Monitoring

Continue monitoring until the abnormality resolves if any of the following is present (even in the absence of symptoms) after 6 hours:

  • the heart rate 6 hours postdose is less than 45 beats per minute (bpm) in adults, less than 55 bpm in pediatric patients 12 years of age and older, or less than 60 bpm in pediatric patients 10 or 11 years of age;
  • the heart rate 6 hours postdose is at the lowest value postdose suggesting that the maximum pharmacodynamic effect on the heart may not have occurred;
  • the ECG 6 hours postdose shows new onset second degree or higher atrioventricular (AV) block.

If postdose symptomatic bradycardia occurs, initiate appropriate management, begin continuous ECG monitoring, and continue monitoring until the symptoms have resolved if no pharmacological treatment is required. If pharmacological treatment is required, continue monitoring overnight and repeat 6-hour monitoring after the second dose.

Overnight Monitoring

Continuous overnight ECG monitoring in a medical facility should be instituted:

  • in patients that require pharmacologic intervention for symptomatic bradycardia. In these patients, the first-dose monitoring strategy should be repeated after the second dose of Fingolimod Capsules;
  • in patients with some preexisting heart and cerebrovascular conditions [see Warnings and Precautions (5.1)];
  • in patients with a prolonged QTc interval before dosing or during 6-hour observation, or at additional risk for QT prolongation, or on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes [see Warnings and Precautions (5.1), Drug Interactions (7.1)];
  • in patients receiving concurrent therapy with drugs that slow heart rate or AV conduction [see Drug Interactions (7.5)].

2.5 Monitoring After Reinitiation of Therapy Following Discontinuation

When restarting Fingolimod Capsules after discontinuation for more than 14 days after the first month of treatment, perform first-dose monitoring, because effects on heart rate and AV conduction may recur on reintroduction of Fingolimod Capsules treatment [see Dosage and Administration (2.4)]. The same precautions (first-dose monitoring) as for initial dosing are applicable. Within the first 2 weeks of treatment, first-dose procedures are recommended after interruption of 1 day or more; during Weeks 3 and 4 of treatment, first-dose procedures are recommended after treatment interruption of more than 7 days.


Fingolimod Capsules are available as:

  • 0.5 mg capsules are size “3” hard gelatin capsules having white opaque cap imprinted “0.5 mg” and white opaque body imprinted “MF” with black ink, filled with white to off white colored fine powder.


Fingolimod Capsules are contraindicated in patients who have:

  • in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization or Class III/IV heart failure
  • a history or presence of Mobitz Type II second-degree or third-degree AV block or sick sinus syndrome, unless patient has a functioning pacemaker [see Warnings and Precautions (5.1)]
  • a baseline QTc interval ≥ 500 msec
  • cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs
  • had a hypersensitivity reaction to fingolimod or any of the excipients in Fingolimod Capsules. Observed reactions include rash, urticaria and angioedema upon treatment initiation [see Warnings and Precautions (5.14)].


5.1 Bradyarrhythmia and Atrioventricular Blocks

Because of a risk for bradyarrhythmia and AV blocks, patients should be monitored during Fingolimod Capsules treatment initiation [see Dosage and Administration (2.4)].

Reduction in Heart Rate

After the first dose of Fingolimod Capsules, the heart rate decrease starts within an hour. On Day 1, the maximum decline in heart rate generally occurs within 6 hours and recovers, although not to baseline levels, by 8 to 10 hours postdose. Because of physiological diurnal variation, there is a second period of heart rate decrease within 24 hours after the first dose. In some patients, heart rate decrease during the second period is more pronounced than the decrease observed in the first 6 hours. Heart rates below 40 bpm in adults, and below 50 bpm in pediatric patients occurred rarely. In controlled clinical trials in adult patients, adverse reactions of symptomatic bradycardia following the first dose were reported in 0.6% of patients receiving Fingolimod Capsules 0.5 mg and in 0.1% of patients on placebo. Patients who experienced bradycardia were generally asymptomatic, but some patients experienced hypotension, dizziness, fatigue, palpitations, and/or chest pain that usually resolved within the first 24 hours on treatment.

Patients with some preexisting conditions (e.g., ischemic heart disease, history of myocardial infarction, congestive heart failure, history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, history of symptomatic bradycardia, history of recurrent syncope, severe untreated sleep apnea, AV block, sinoatrial heart block) may poorly tolerate the Fingolimod Capsules-induced bradycardia, or experience serious rhythm disturbances after the first dose of Fingolimod Capsules. Prior to treatment with Fingolimod Capsules, these patients should have a cardiac evaluation by a physician appropriately trained to conduct such evaluation, and if treated with Fingolimod Capsules, should be monitored overnight with continuous ECG in a medical facility after the first dose.

Since initiation of Fingolimod Capsules treatment, results in decreased heart rate and may prolong the QT interval, patients with a prolonged QTc interval (> 450 msec adult and pediatric males, > 470 msec adult females, or > 460 msec pediatric females) before dosing or during 6-hour observation, or at additional risk for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome), or on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) should be monitored overnight with continuous ECG in a medical facility.

Following the second dose, a further decrease in heart rate may occur when compared to the heart rate prior to the second dose, but this change is of a smaller magnitude than that observed following the first dose. With continued dosing, the heart rate returns to baseline within 1 month of chronic treatment. Clinical data indicate effects of Fingolimod Capsules on heart rate are maximal after the first dose although milder effects on heart rate may persist for, on average, 2 to 4 weeks after initiation of therapy at which time heart rate generally returns to baseline. Physicians should continue to be alert to patient reports of cardiac symptoms.

Atrioventricular Blocks

Initiation of Fingolimod Capsules treatment has resulted in transient AV conduction delays. In controlled clinical trials in adult patients, first-degree AV block after the first dose occurred in 4.7% of patients receiving Fingolimod Capsules and 1.6% of patients on placebo. In a study of 697 patients with available 24-hour Holter monitoring data after their first dose (N = 351 receiving Fingolimod Capsules and N = 346 on placebo), second-degree AV blocks (Mobitz Types I [Wenckebach] or 2:1 AV blocks) occurred in 4% (N = 14) of patients receiving Fingolimod Capsules and 2% (N = 7) of patients on placebo. Of the 14 patients receiving Fingolimod Capsules, 7 patients had 2:1 AV block (5 patients within the first 6 hours postdose and 2 patients after 6 hours postdose). All second-degree AV blocks on placebo were Mobitz Type I and occurred after the first 12 hours postdose. The conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hours on treatment, but they occasionally required treatment with atropine or isoproterenol.

Postmarketing Experience

In the postmarketing setting, third-degree AV block and AV block with junctional escape have been observed during the first-dose 6-hour observation period with Fingolimod Capsules. Isolated delayed onset events, including transient asystole and unexplained death, have occurred within 24 hours of the first dose. These events were confounded by concomitant medications and/or preexisting disease, and the relationship to Fingolimod Capsules is uncertain. Cases of syncope were also reported after the first dose of Fingolimod Capsules.

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