Fingolimod: Uses, Dosage, Side Effects & Warnings

Q: Who makes Fingolimod?

Fingolimod is listed by 20 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Apotex Corp., Ascend Laboratories, LLC.

Q: Has Fingolimod been recalled?

The FDA enforcement database lists 1 recall for Fingolimod, most recently D-0925-2023 (class ii): Failed Dissolution Specifications

Uses

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. Fingolimod Capsules are sphingosine 1-phosphate receptor modulator 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. ( 1 )

Dosage and administration

Assessments are required prior to initiating Fingolimod Capsules ( 2.1 ) Recommended dosage for adults and pediatric patients (10 years of age and older) weighing more than 40 kg: 0.5 mg orally once daily, with or without food. ( 2.2 , 2.3 ) Recommended dosage for pediatric patients (10 years of age and above) weighing less than or equal to 40 kg: 0.25 mg orally once daily, with or without food. ( 2.2 , 2.3 ). First-Dose Monitoring (including reinitiation after discontinuation greater than 14 days and dose increases): oObserve all patients for bradycardia for at least 6 hours; monitor pulse and blood pressure hourly. Electrocardiograms (ECGs) prior to dosing and at end of observation period required. ( 2.4 ) oMonitor until resolution if heart rate < 45 beats per minute (bpm) in adults, < 55 bpm in patients aged 12 years and above, or < 60 bpm in pediatric patients aged 10 to below 12 years, atrioventricular (AV) block, or if lowest postdose heart rate is at the end of the observation period. ( 2.4 ) oMonitor symptomatic bradycardia with ECG until resolved. Continue overnight if intervention is required; repeat first-dose monitoring for second dose. ( 2.4 ) oObserve patients overnight if at higher risk of symptomatic bradycardia, heart block, prolonged QTc interval, or if taking drugs with known risk of torsades de pointes. ( 2.4 , 7.1 ) 2.1 Assessment Prior to Initiating Fingolimod Capsules 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) ]. Ophthalmic Assessment Obtain a baseline evaluation of the fundus, including the macula, near the start of the treatment with fingolimod capsules [see Warningsand Precautions (5.4) ]. Skin Examination Obtain a baseline skin examination prior to or shortly after initiation of fingolimod capsules. If a suspicious skin lesion is observed, itshould be promptly evaluated [see Warnings and Precautions (5.12) ]. 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) ]. Vaccinations 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 45beats 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 higheratrioventricular (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.

Dosage forms and strengths

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, filledwith white to off white colored fine powder. 0.5 mg hard capsules ( 3 )

Contraindications

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) ]. Recent myocardial infarction, unstable angina, stroke, transient ischemic attack(TIA), decompensated heart failure with hospitalization, or Class III/IV heart failure. ( 4 ) History of Mobitz Type II 2nd degree or 3rd degree AV block or sick sinus syndrome, unless patient has a pacemaker. ( 4 ) Baseline QTc interval ≥500 msec. ( 4 ) Cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs. ( 4 ) Hypersensitivity to fingolimod or its excipients. ( 4 )

Warnings and precautions

Infections : Fingolimod Capsules may increase the risk. Obtain a complete blood count (CBC) before initiating treatment. Monitor for infection during treatment and for 2 months after discontinuation. Do not start in patients with active infections. ( 5.2 ) Progressive Multifocal Leukoencephalopathy (PML) : Withhold Fingolimod Capsules at the first sign or symptom suggestive of PML. ( 5.3 ) Macular Edema: Increases the risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with fingolimod capsules. Conduct an evaluation of the fundus, including the macula, 3 to 4 months after treatment start, periodically while on therapy and any time there is a change in vision. Consider discontinuing fingolimod capsules if macular edema develops. Diabetes mellitus and uveitis increase the risk. ( 5.4 ) Liver Injury : Obtain liver enzyme results before initiation and periodically during treatment. Closely monitor patients with severe hepatic impairment. Discontinue if there is evidence of liver injury without other cause. ( 5.5 , 8.6 , 12.3 ) Posterior Reversible Encephalopathy Syndrome (PRES) : If suspected, discontinue Fingolimod Capsules. ( 5.6 ) Respiratory Effects : Evaluate when clinically indicated. ( 5.7 ) Fetal Risk : May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 2 months after stopping Fingolimod Capsules. ( 5.8 , 8.1 , 8.3 ) Severe Increase in Disability After Stopping Fingolimod Capsules : Monitor for development of severe increase in disability following discontinuation and begin appropriate treatment as needed. ( 5.9 ) Tumefactive MS : Consider when severe MS relapse occurs during treatment or after discontinuation. Obtain imaging and begin treatment as needed.( 5.10 ) Increased Blood Pressure (BP): Monitor BP in adult and pediatric patients during treatment. ( 5.11 ) Malignancies : Skin examination prior to or shortly after the start of treatment and periodically thereafter is recommended. Suspicious skin lesions should be evaluated. ( 5.12 ) 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.

Side effects

The following serious adverse reactions are described elsewhere in labeling: Bradyarrhythmia and Atrioventricular Blocks [ see Warnings and Precautions (5.1) ] Infections [ see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [ see Warnings and Precautions (5.3) ] Macular Edema [ see Warnings and Precautions (5.4) ] Liver Injury [ see Warnings and Precautions (5.5) ] Posterior Reversible Encephalopathy Syndrome [ see Warnings and Precautions (5.6) ] Respiratory Effects [ see Warnings and Precautions (5.7) ] Fetal Risk [ see Warnings and Precautions (5.8) ] Severe Increase in Disability After Stopping Fingolimod Capsules [ see Warnings and Precautions (5.9) ] Tumefactive Multiple Sclerosis [ see Warnings and Precautions (5.10) ] Increased Blood Pressure [ see Warnings and Precautions (5.11) ] Malignancies [ see Warnings and Precautions (5.12) ] Immune System Effects Following Fingolimod Capsules Discontinuation [ see Warnings and Precautions (5.13) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.14)] Most common adverse reactions (incidence ≥ 10% and greater than placebo): Headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults In clinical trials (Studies 1, 2, and 3), a total of 1,212 patients with relapsing forms of multiple sclerosis received Fingolimod Capsules 0.5 mg. This included 783 patients who received Fingolimod Capsules 0.5 mg in the 2-year placebo-controlled trials (Studies 1 and 3) and 429 patients who received Fingolimod Capsules 0.5 mg in the 1-year active-controlled trial (Study 2). The overall exposure in the controlled trials was equivalent to 1,716 person-years. Approximately 1,000 patients received at least 2 years of treatment with Fingolimod Capsules 0.5 mg. In all clinical studies, including uncontrolled extension studies, the exposure to Fingolimod Capsules 0.5 mg was approximately 4,119 person-years. In placebo-controlled trials, the most frequent adverse reactions (incidence ≥10% and greater than placebo) for Fingolimod Capsules 0.5 mg were headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity. Adverse events that led to treatment discontinuation and occurred in more than 1% of patients taking Fingolimod Capsules 0.5 mg, were serum transaminase elevations (4.7% compared to 1% on placebo) and basal cell carcinoma (1% compared to 0.5% on placebo). Table 1 lists adverse reactions in clinical studies in adults that occurred in ≥ 1% of Fingolimod-treated patients and ≥ 1% higher rate than for placebo. Table 1: Adverse Reactions Reported in Adult Studies 1 and 3 (Occurring in ≥1% of Patients and Reported for Fingolimod Capsules 0.5 mg at ≥1% Higher Rate Than for Placebo) Adverse drug reactions Fingolimod Capsules 0.5 mg N=783 % Placebo N=773 % Infections Influenza 11 8 Sinusitis 11 8 Bronchitis 8 5 Herpes zoster 2 1 Tinea versicolor 2 <1 Cardiac disorders Bradycardia 3 1 Nervous system disorders Headache 25 24 Migraine 6 4 Gastrointestinal disorders Nausea 13 12 Diarrhea 13 10 Abdominal pain 11 10 General disorders and administration-site conditions Asthenia 2 1 Musculoskeletal and connective tissue disorders Back pain 10 9 Pain in extremity 10 7 Skin and subcutaneous tissue disorders Alopecia 3 2 Actinic keratosis 2 1 Investigations Liver transaminase elevations (ALT/GGT/AST) 15 4 Blood triglycerides increased 3 1 Respiratory, thoracic, and mediastinal disorders Cough 12 11 Dyspnea 9 7 Eye disorders Vision blurred 4 2 Vascular disorders Hypertension 8 4 Blood and lymphatic system disorders Lymphopenia 7 <1 Leukopenia 2 <1 Neoplasms benign, malignant, and unspecified (including cysts and polyps) Skin papilloma 3 2 Basal cell carcinoma 2 1 Abbreviations: ALT, alanine transaminase; AST, aspartate transferase; GGT, gamma-glutamyl transferase. Adverse reactions of seizure, dizziness, pneumonia, eczema, and pruritus were also reported in Studies 1 and 3, but did not meet the reporting rate criteria for inclusion in Table 1 (difference was less than 1%). Adverse reactions with Fingolimod Capsules 0.5 mg in Study 2, the 1-year active-controlled (versus interferon beta-1a) study were generally similar to those in Studies 1 and 3. Vascular Events Vascular events, including ischemic and hemorrhagic strokes, and peripheral arterial occlusive disease were reported in premarketing clinical trials in patients who received Fingolimod Capsules doses (1.25 mg to 5 mg) higher than recommended for use in MS. Similar events have been reported with Fingolimod Capsules in the postmarketing setting although a causal relationship has not been established. Seizure Cases of seizures, including status epilepticus, have been reported with the use of Fingolimod Capsules in clinical trials and in the postmarketing setting in adults [ see Adverse Reactions (6.2) ]. In adult clinical trials, the rate of seizures was 0.9% in Fingolimod-treated patients and 0.3% in placebo-treated patients. It is unknown whether these events were related to the effects of multiple sclerosis alone, to Fingolimod Capsules, or to a combination of both. Pediatric Patients 10 Years of Age and Older In the controlled pediatric trial (Study 4), the safety profile in pediatric patients receiving Fingolimod Capsules 0.25 mg or 0.5 mg daily was similar to that seen in adult patients.

Drug interactions

Systemic Ketoconazole : Monitor during concomitant use. ( 7.2 , 12.3 ) Vaccines : Avoid live attenuated vaccines during, and for 2 months after stopping fingolimod treatment. ( 5.2 , 7.3 ) 7.1 QT Prolonging Drugs Fingolimod Capsules has not been studied in patients treated with drugs that prolong the QT interval. Drugs that prolong the QT interval have been associated with cases of torsades de pointes in patients with bradycardia. Since initiation of Fingolimod Capsules treatment results in decreased heart rate and may prolong the QT interval, patients on 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 [ see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. 7.2 Ketoconazole The blood levels of fingolimod and fingolimod-phosphate are increased by 1.7-fold when used concomitantly with ketoconazole. Patients who use Fingolimod Capsules and systemic ketoconazole concomitantly should be closely monitored, as the risk of adverse reactions is increased. 7.3 Vaccines Fingolimod Capsules reduces the immune response to vaccination. Vaccination may be less effective during and for up to 2 months after discontinuation of treatment with Fingolimod Capsules [ see Clinical Pharmacology (12.2) ] . Avoid the use of live attenuated vaccines during and for 2 months after treatment with Fingolimod Capsules because of the risk of infection. It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating Fingolimod Capsules therapy. 7.4 Antineoplastic, Immunosuppressive, or Immune-Modulating Therapies Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with Fingolimod Capsules. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating Fingolimod Capsules [ see Warnings and Precautions (5.2) ]. 7.5 Drugs That Slow Heart Rate or Atrioventricular Conduction (e.g., beta blockers or diltiazem) Experience with Fingolimod Capsules in patients receiving concurrent therapy with drugs that slow the heart rate or AV conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers, such as diltiazem or verapamil) is limited. Because initiation of Fingolimod Capsules treatment may result in an additional decrease in heart rate, concomitant use of these drugs during Fingolimod Capsules initiation may be associated with severe bradycardia or heart block. Seek advice from the physician prescribing these drugs regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating Fingolimod Capsules. Patients who cannot switch should have overnight continuous ECG monitoring after the first dose [ see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. 7.6 Laboratory Test Interaction Because Fingolimod Capsules reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to evaluate the lymphocyte subset status of a patient treated with Fingolimod Capsules. A recent CBC should be available before initiating treatment with Fingolimod Capsules.

Use in specific populations

8.1 Pregnancy Risk Summary Available observational pregnancy registry data suggest that use of Fingolimod Capsules are associated with an increased prevalenceof major birth defects in comparison to the general population. However, limitations in the number of exposed pregnant women and inthe study design preclude definitive conclusions (see Data). Data from prospective reports to the pregnancy registry are currently notsufficient to allow for an adequate assessment of the drug-associated risk for miscarriage. Based on findings from animal studies, Fingolimod Capsules may cause fetal harm when administered to a pregnant woman. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m2) basis. The most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis (see Data) . Advise pregnant women of the potential risk to a fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations In females planning to become pregnant, Fingolimod Capsules should be stopped 2 months before planned conception. The possibility of severe increase in disability should be considered in women who discontinue or are considering discontinuation of Fingolimod Capsules because of pregnancy or planned pregnancy. In many of the cases in which increase in disability was reported after stopping Fingolimod Capsules, patients had stopped Fingolimod Capsules because of pregnancy or planned pregnancy [ see Warnings and Precautions (5.9) ] . Data Human Data In a prospective observational GILENYA pregnancy registry (GPR) (2011 to 2024), the rate of major birth defects among 147 live births, stillbirths, or terminations of pregnancy due to fetal anomalies from women who were administered fingolimod during the first trimesterwas 8.2% (95% CI: 4.3 to 13.8) using the European Registration of Congenital Anomalies and Twin classification and 10.9% (95%CI: 6.4 to 17.1) using the Metropolitan Atlanta Congenital Defects Program classification. The most frequent major birth defects werecongenital heart defects, renal/urinary malformations, and limb/musculoskeletal malformations. Study limitations include no adjustmentfor confounders, no re-adjudication in case of spontaneous resolution, lack of an internal comparator cohort, and small sample size. In fingolimod prospective pharmacovigilance data, the most frequent major birth defect types were similar to those reported in the GPR. The pattern of malformations reported for Fingolimod Capsules is similar to that observed in the general population. There is noevidence of clustering of specific birth defects with Fingolimod Capsules. Animal Data When fingolimod was orally administered to pregnant rats during the period of organogenesis (0, 0.03, 0.1, and 0.3 mg/kg/day or 0, 1, 3, and 10 mg/kg/day), increased incidences of fetal malformations and embryofetal deaths were observed at all but the lowest dose tested (0.03 mg/kg/day), which is less than the recommended human dose (RHD) on a mg/m2 basis. Oral administration to pregnant rabbits during organogenesis (0, 0.5, 1.5, and 5 mg/kg/day) resulted in increased incidences of embryofetal mortality and fetal growth retardation at the mid and high doses. The no-effect dose for these effects in rabbits (0.5 mg/kg/day) is approximately 20 times the RHD on a mg/m2 basis. When fingolimod was orally administered to female rats during pregnancy and lactation (0, 0.05, 0.15, and 0.5 mg/kg/day), pup survival was decreased at all doses and a neurobehavioral (learning) deficit was seen in offspring at the high dose. The low-effect dose of 0.05 mg/kg/day is similar to the RHD on a mg/m2 basis. 8.2 Lactation Risk Summary There are no data on the presence of fingolimod in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Fingolimod is excreted in the milk of treated rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fingolimod Capsules and any potential adverse effects on the breastfed infant from Fingolimod Capsules or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing The pregnancy status of females of reproductive potential should be verified prior to starting treatment with Fingolimod Capsules [ see Use in Specific Populations (8.1) ]. Contraception Before initiation of Fingolimod Capsules treatment, females of reproductive potential should be counseled on the potential for a serious risk to the fetus and the need for effective contraception during treatment with Fingolimod Capsules [ see Warnings and Precautions (5.8) and Use in Specific Populations (8.1) ]. Since it takes approximately 2 months to eliminate the compound from the body after stopping treatment, the potential risk to the fetus may persist and women should use effective contraception during this period [ see Warnings and Precautions (5.8 , 5.13) ].

Pregnancy

8.1 Pregnancy Risk Summary Available observational pregnancy registry data suggest that use of Fingolimod Capsules are associated with an increased prevalenceof major birth defects in comparison to the general population. However, limitations in the number of exposed pregnant women and inthe study design preclude definitive conclusions (see Data). Data from prospective reports to the pregnancy registry are currently notsufficient to allow for an adequate assessment of the drug-associated risk for miscarriage. Based on findings from animal studies, Fingolimod Capsules may cause fetal harm when administered to a pregnant woman. In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryolethality, when given to pregnant animals. In rats, the highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m2) basis. The most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect. The receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis (see Data) . Advise pregnant women of the potential risk to a fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations In females planning to become pregnant, Fingolimod Capsules should be stopped 2 months before planned conception. The possibility of severe increase in disability should be considered in women who discontinue or are considering discontinuation of Fingolimod Capsules because of pregnancy or planned pregnancy. In many of the cases in which increase in disability was reported after stopping Fingolimod Capsules, patients had stopped Fingolimod Capsules because of pregnancy or planned pregnancy [ see Warnings and Precautions (5.9) ] . Data Human Data In a prospective observational GILENYA pregnancy registry (GPR) (2011 to 2024), the rate of major birth defects among 147 live births, stillbirths, or terminations of pregnancy due to fetal anomalies from women who were administered fingolimod during the first trimesterwas 8.2% (95% CI: 4.3 to 13.8) using the European Registration of Congenital Anomalies and Twin classification and 10.9% (95%CI: 6.4 to 17.1) using the Metropolitan Atlanta Congenital Defects Program classification. The most frequent major birth defects werecongenital heart defects, renal/urinary malformations, and limb/musculoskeletal malformations. Study limitations include no adjustmentfor confounders, no re-adjudication in case of spontaneous resolution, lack of an internal comparator cohort, and small sample size. In fingolimod prospective pharmacovigilance data, the most frequent major birth defect types were similar to those reported in the GPR. The pattern of malformations reported for Fingolimod Capsules is similar to that observed in the general population. There is noevidence of clustering of specific birth defects with Fingolimod Capsules. Animal Data When fingolimod was orally administered to pregnant rats during the period of organogenesis (0, 0.03, 0.1, and 0.3 mg/kg/day or 0, 1, 3, and 10 mg/kg/day), increased incidences of fetal malformations and embryofetal deaths were observed at all but the lowest dose tested (0.03 mg/kg/day), which is less than the recommended human dose (RHD) on a mg/m2 basis. Oral administration to pregnant rabbits during organogenesis (0, 0.5, 1.5, and 5 mg/kg/day) resulted in increased incidences of embryofetal mortality and fetal growth retardation at the mid and high doses. The no-effect dose for these effects in rabbits (0.5 mg/kg/day) is approximately 20 times the RHD on a mg/m2 basis. When fingolimod was orally administered to female rats during pregnancy and lactation (0, 0.05, 0.15, and 0.5 mg/kg/day), pup survival was decreased at all doses and a neurobehavioral (learning) deficit was seen in offspring at the high dose. The low-effect dose of 0.05 mg/kg/day is similar to the RHD on a mg/m2 basis.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of Fingolimod Capsules for the treatment of relapsing forms of multiple sclerosis in pediatric patients 10 to less than 18 years of age were established in one randomized, double-blind clinical study in 215 patients (Fingolimod Capsules n = 107; intramuscular interferon (IFN) beta-1a n = 108) [ see Clinical Studies (14.2) ]. In the controlled pediatric study, the safety profile in pediatric patients (10 to less than 18 years of age) receiving Fingolimod Capsules 0.25 mg or 0.5 mg daily was similar to that seen in adult patients. In the pediatric study, cases of seizures were reported in 5.6% of fingolimod-treated patients and 0.9% of interferon beta-1a-treated patients. It is recommended that pediatric patients, if possible, complete all immunizations in accordance with current immunization guidelines prior to initiating Fingolimod Capsules therapy. Safety and effectiveness of Fingolimod Capsules in pediatric patients below the age of 10 years have not been established. Juvenile Animal Toxicity Data In a study in which fingolimod (0.3, 1.5, or 7.5 mg/kg/day) was orally administered to young rats from weaning through sexual maturity, changes in bone mineral density and persistent neurobehavioral impairment (altered auditory startle) were observed at all doses. Delayed sexual maturation was noted in females at the highest dose tested and in males at all doses. The bone changes observed in fingolimod-treated juvenile rats are consistent with a reported role of S1P in the regulation of bone mineral homeostasis. When fingolimod (0.5 or 5 mg/kg/day) was orally administered to rats from the neonatal period through sexual maturity, a marked decrease in T-cell dependent antibody response was observed at both doses. This effect had not fully recovered by 6 to 8 weeks after the end of treatment. Overall, a no-effect dose for adverse developmental effects in juvenile animals was not identified.

Geriatric use

8.6 Hepatic Impairment Because fingolimod, but not fingolimod-phosphate, exposure is doubled in patients with severe hepatic impairment, patients with severe hepatic impairment should be closely monitored, as the risk of adverse reactions may be greater [ see Warnings and Precautions (5.5) , Clinical Pharmacology (12.3) ]. No dose adjustment is needed in patients with mild or moderate hepatic impairment.

Overdosage

Fingolimod Capsules can induce bradycardia as well as AV conduction blocks (including complete AV block). The decline in heart rate usually starts within 1 hour of the first dose and is maximal within 6 hours in most patients [ see Warnings and Precautions (5.1) ]. In case of Fingolimod Capsules overdosage, observe patients overnight with continuous ECG monitoring in a medical facility, and obtain regular measurements of blood pressure [ see Dosage and Administration (2.4) ]. Neither dialysis nor plasma exchange results in removal of fingolimod from the body.

Description

Fingolimod, USP is a sphingosine 1-phosphate receptor modulator. Chemically, fingolimod, USP is 2-Amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol hydrochloride. Its structure is shown below: Fingolimod hydrochloride, USP is a white to practically white powder that is freely soluble in water and in alcohol and soluble in propylene glycol. It has a molecular weight of 343.93 g/mol. Fingolimod Capsules are provided as 0.5 mg hard gelatin capsules for oral use. Each 0.5 mg capsule contains 0.56 mg of fingolimod hydrochloride, USP equivalent to 0.5 mg of fingolimod, USP. Each Fingolimod Capsules 0.5 mg contains the following inactive ingredients: fumaric acid, stearic acid, pregelatinized starch and empty hard gelatin capsules. The hard gelatin capsule shell contains gelatin, titanium dioxide, and is imprinted with black ink. Black imprinting ink contains shellac, propylene glycol, black iron oxide and potassium hydroxide. Fingolimod chemical structure

Mechanism of action

12.1 Mechanism of Action Fingolimod is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

How supplied

16.1 How Supplied 0.5 mg Fingolimod capsules are supplied as follows: 0.5 mg Fingolimod Capsules are size “3” hard gelatin capsules having white opaque cap imprinted “0.5mg” and white opaque body imprinted “MF” with black ink, filled with white to off white colored fine powder. 28 Unit-Dose capsules containing (2 blisters of 14 capsules in a carton) NDC 72205-227-32 30 Count bottle NDC 72205-227-30 16.2 Storage and Handling Fingolimod Capsules should be stored at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature]. Protect from moisture. 16.1 How Supplied 0.5 mg Fingolimod capsules are supplied as follows: 0.5 mg Fingolimod Capsules are size “3” hard gelatin capsules having white opaque cap imprinted “0.5mg” and white opaque body imprinted “MF” with black ink, filled with white to off white colored fine powder. 28 Unit-Dose capsules containing (2 blisters of 14 capsules in a carton) NDC 72205-227-32 30 Count bottle NDC 72205-227-30

Storage

16.2 Storage and Handling Fingolimod Capsules should be stored at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature]. Protect from moisture.

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Tell patients not to discontinue Fingolimod Capsules without first discussing this with the prescribing healthcare provider. Advise patients to contact their healthcare provider if they accidently take more Fingolimod Capsules than prescribed. Cardiac Effects Advise patients that initiation of Fingolimod Capsules treatment results in a transient decrease in heart rate. Inform patients that they will need to be observed in the healthcare provider's office or other facility for at least 6 hours after the first dose, after reinitiation if treatment is interrupted or discontinued for certain periods, and after the dosage is increased [ see Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. Risk of Infections Inform patients that they may have an increased risk of infections, some of which could be life-threatening, when taking Fingolimod Capsules, and that they should contact their healthcare providerif they develop symptoms of infection. Advise patients that the use of some vaccines should be avoided during treatment with Fingolimod Capsules and for 2 months after discontinuation. Recommend to patients that they delay treatment with Fingolimod Capsules until after VZV vaccination if they have not had chickenpox or a previous VZV vaccination. Inform patients that prior or concomitant use of drugs that suppress the immune system may increase the risk of infection [ see Warnings and Precautions (5.2) ]. Progressive Multifocal Leukoencephalopathy Inform patients that cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients who received Fingolimod Capsules. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their healthcare provider ifthey develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [ see Warnings and Precautions (5.3) ]. Macular Edema Advise patients that Fingolimod Capsules may cause macular edema, and that they should obtain an eye exam near the start of treatment with fingolimod capsules, have their eyes monitored periodically by an eye care professional while receiving therapy, and contact their healthcare provider if they experience any changes in their vision while taking fingolimod capsules. Inform patients with diabetes mellitus or a history of uveitis that their risk of macular edema is increased [see Warnings and Precautions (5.4 )]. Hepatic Effects Inform patients that Fingolimod Capsules may cause liver injury. Advise patients that they should contact their healthcare provider ifthey have any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine [ see Warnings and Precautions (5.5) ]. Posterior Reversible Encephalopathy Syndrome Advise patients to immediately report to their healthcare provider any symptoms involving sudden onset of severe headache, altered mental status, visual disturbances, or seizure. Inform patients that delayed treatment could lead to permanent neurological sequelae [ see Warnings and Precautions (5.6) ]. Respiratory Effects Advise patients that they should contact their healthcare providerif they experience new onset or worsening of dyspnea [ see Warnings and Precautions (5.7) ]. Fetal Risk Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [ see Warnings and Precautions (5.8) and Use in Specific Populations (8.1 , 8.3) ]. Advise female patients of reproductive potential to use effective contraception during treatment with Fingolimod Capsules and for 2 months after the final dose [ see Use in Specific Populations (8.3) ]. Severe Increase in Disability After Stopping Fingolimod Capsules Inform patients that severe increase in disability has been reported after discontinuation of Fingolimod Capsules. Advise patients to contact their healthcare provider ifthey develop worsening symptoms of MS following discontinuation of Fingolimod Capsules [ see Warnings and Precautions (5.9) ]. Malignancies Advise patients that the risk of basal cell carcinoma and melanoma is increased with use of fingolimod capsules and that cases of squamous cell carcinoma, Merkel cell carcinoma, and Kaposi’s sarcoma have been reported. Advise patients that any suspicious skin lesions should be promptly evaluated. Advise patients to limit exposure to sunlight and ultraviolet light by wearing protective clothing and using a sunscreen with a high protection factor. Inform patients that lymphoma has also occurred in patients receiving Fingolimod Capsules [see Warnings and Precautions (5.12) ]. Persistence of Fingolimod Capsules Effects After Drug Discontinuation Advise patients that Fingolimod Capsules remains in the blood and continues to have effects, including decreased blood lymphocyte counts, for up to 2 months following the last dose [ see Warnings and Precautions (5.13) ]. Hypersensitivity Reactions Advise patients that Fingolimod Capsules may cause hypersensitivity reactions, including rash, urticaria, and angioedema. Advise patients to contact their healthcare providerif they have any symptoms associated with hypersensitivity [ see Warnings and Precautions (5.14) ]. Pregnancy Instruct patients that if they are pregnant or plan to become pregnant while taking Fingolimod Capsules they should inform theirhealthcare provider. [see Use in Specific Populations (8.1 )].

Active ingredients

Fingolimod Hydrochloride in 19 products
Fingolimod in 1 product

Fingolimod NDC products (20)

NDC	Strength & form	Labeler	Type
62332-228	Fingolimod Hydrochloride .5 mg/1 Capsule	Alembic Pharmaceuticals Inc.	ANDA
46708-228	Fingolimod Hydrochloride .5 mg/1 Capsule	Alembic Pharmaceuticals Limited	ANDA
60505-4332	Fingolimod Hydrochloride .5 mg/1 Capsule	Apotex Corp.	ANDA
67877-476	Fingolimod Hydrochloride .5 mg/1 Capsule	Ascend Laboratories, LLC	ANDA
65862-952	Fingolimod Hydrochloride .5 mg/1 Capsule	Aurobindo Pharma Limited	ANDA
42291-048	Fingolimod Hydrochloride .5 mg/1 Capsule	AvKARE	ANDA
70377-019	Fingolimod Hydrochloride .5 mg/1 Capsule	Biocon Pharma Inc.	ANDA
31722-889	Fingolimod Hydrochloride .5 mg/1 Capsule	Camber Pharmaceuticals, Inc.	ANDA
82249-385	Fingolimod Hydrochloride .5 mg/1 Capsule	CivicaScript LLC	ANDA
43598-285	Fingolimod Hydrochloride .5 mg/1 Capsule	Dr. Reddy's Laboratories Inc	ANDA
68462-166	Fingolimod Hydrochloride .5 mg/1 Capsule	Glenmark Pharmaceuticals Inc., USA	ANDA
72205-227	Fingolimod Hydrochloride .5 mg/1 Capsule	Novadoz Pharmaceuticals LLC	ANDA
82009-143	Fingolimod Hydrochloride .5 mg/1 Capsule	Quallent Pharmaceuticals Health LLC	ANDA
64980-449	Fingolimod Hydrochloride .5 mg/1 Capsule	Rising Pharma Holdings, Inc.	ANDA
43547-003	Fingolimod .5 mg/1 Capsule	Solco Healthcare US, LLC	ANDA
62756-064	Fingolimod Hydrochloride .5 mg/1 Capsule	Sun Pharmaceutical Industries, Inc.	ANDA
0480-7820	Fingolimod Hydrochloride .5 mg/1 Capsule	Teva Pharmaceuticals, Inc.	ANDA
72865-257	Fingolimod Hydrochloride .5 mg/1 Capsule	XLCare Pharmaceuticals Inc.	ANDA
70771-1603	Fingolimod Hydrochloride .5 mg/1 Capsule	Zydus Lifesciences Limited	ANDA
68382-912	Fingolimod Hydrochloride .5 mg/1 Capsule	Zydus Pharmaceuticals USA Inc.	ANDA

Fingolimod recalls

D-0925-2023 Jul 26, 2023 · Class II · Ongoing
Failed Dissolution Specifications

Frequently asked questions

What is Fingolimod used for?

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. Fingolimod Capsules are sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to…

What are the side effects of Fingolimod?

The following serious adverse reactions are described elsewhere in labeling: Bradyarrhythmia and Atrioventricular Blocks [ see Warnings and Precautions (5.1) ] Infections [ see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [ see Warnings and Precautions (5.3) ] Macular Edema [ see Warnings and Precautions (5.4) ] Liver Injury [ see Warnings and Precautions (5.5) ]… See the full label for the complete list.

Who makes Fingolimod?

Fingolimod is listed by 20 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Apotex Corp., Ascend Laboratories, LLC.

Has Fingolimod been recalled?

The FDA enforcement database lists 1 recall for Fingolimod, most recently D-0925-2023 (class ii): Failed Dissolution Specifications