FINGOLIMOD LAURYL: 189 Adverse Event Reports & Safety Profile
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Active Ingredient: FINGOLIMOD LAURYL SULFATE · Drug Class: Sphingosine 1-Phosphate Receptor Modulators [MoA] · Route: ORAL · Manufacturer: Cycle Pharmaceuticals Ltd · FDA Application: 214962 · HUMAN PRESCRIPTION DRUG · FDA Label: Available
Patent Expires: Jan 19, 2036 · First Report: 20230112 · Latest Report: 20250813
What Are the Most Common FINGOLIMOD LAURYL Side Effects?
All FINGOLIMOD LAURYL Side Effects by Frequency
| Side Effect | Reports | % of Total | Deaths | Hosp. |
|---|---|---|---|---|
| Heart rate decreased | 26 | 13.8% | 0 | 0 |
| Fatigue | 22 | 11.6% | 0 | 0 |
| Headache | 21 | 11.1% | 0 | 2 |
| Dizziness | 14 | 7.4% | 0 | 1 |
| Somnolence | 11 | 5.8% | 0 | 0 |
| Multiple sclerosis relapse | 9 | 4.8% | 0 | 4 |
| Nausea | 8 | 4.2% | 0 | 0 |
| Asthenia | 6 | 3.2% | 0 | 0 |
| Off label use | 6 | 3.2% | 0 | 0 |
| Abdominal pain upper | 5 | 2.7% | 0 | 0 |
| Hepatic enzyme increased | 5 | 2.7% | 0 | 0 |
| Paraesthesia | 5 | 2.7% | 0 | 0 |
Who Reports FINGOLIMOD LAURYL Side Effects? Age & Gender Data
Most reports from: US. View detailed demographics →
Is FINGOLIMOD LAURYL Getting Safer? Reports by Year
| Year | Reports | Deaths | Hosp. |
|---|---|---|---|
| 2023 | 67 | 0 | 1 |
| 2024 | 58 | 1 | 5 |
| 2025 | 17 | 2 | 4 |
What Is FINGOLIMOD LAURYL Used For?
| Indication | Reports |
|---|---|
| Multiple sclerosis | 163 |
| Product used for unknown indication | 16 |
| Multiple sclerosis relapse | 5 |
FINGOLIMOD LAURYL vs Alternatives: Which Is Safer?
Other Drugs in Same Class: Sphingosine 1-Phosphate Receptor Modulators [MoA]
Official FDA Label for FINGOLIMOD LAURYL
Official prescribing information from the FDA-approved drug label.
Drug Description
Fingolimod is a sphingosine 1-phosphate receptor modulator. Chemically, fingolimod lauryl sulfate is 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol lauryl sulfate. Its structure is shown below: Fingolimod lauryl sulfate is a white to practically white powder that is practically insoluble in water. It has a molecular weight of 573.87 g/mol. TASCENSO ODT is provided as 0.25 mg and 0.5 mg orally disintegrating tablets for oral use. Each orally disintegrating tablet contains 0.25 mg or 0.5 mg of fingolimod (equivalent to 0.47 mg or 0.93 mg of fingolimod lauryl sulfate) and the following inactive ingredients: gelatin, mannitol, medium-chain triglycerides, sodium chloride, and sodium lauryl sulfate.
Chemical
Structure
FDA Approved Uses (Indications)
AND USAGE TASCENSO ODT is 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. TASCENSO ODT is a 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 & Administration
AND ADMINISTRATION Assessments are required prior to initiating TASCENSO ODT ( 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 older) weighing less than or equal to 40 kg: 0.25 mg orally once daily, with or without food ( 2.2 , 2.3 ). Administer TASCENSO ODT with or without water. Place tablet directly on the tongue and allow it to dissolve before swallowing. ( 2.2 ) First-Dose Monitoring (including reinitiation after discontinuation greater than 14 days and dose increases): Observe 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 ) Monitor 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 ) Monitor symptomatic bradycardia with ECG until resolved. Continue overnight if intervention is required; repeat first-dose monitoring for second dose. ( 2.4 ) Observe 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 TASCENSO ODT Cardiac Evaluation Obtain a cardiac evaluation in patients with certain preexisting conditions <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) and Warnings and Precautions (5.1) ]</span>. Prior to starting treatment, determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) , Drug Interactions (7.5) ]</span> .
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 TASCENSO ODT (i.e., within 6 months), review 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 treatment with TASCENSO ODT [see Warnings and Precautions ( 5.4 )] .
Skin Examination
Obtain a baseline skin examination prior to or shortly after initiation of TASCENSO ODT. If a suspicious skin lesion is observed, it should 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 prior to initiating treatment with TASCENSO ODT [see Warnings and Precautions (5.2) , Drug Interactions (7.4) ].
Vaccinations
Prior to initiating TASCENSO ODT, test patients for antibodies to varicella zoster virus (VZV). VZV vaccination of antibody- negative patients is recommended prior to commencing treatment with TASCENSO ODT [see Warnings and Precautions (5.2) ] . It is recommended that pediatric patients if possible, complete all other immunizations in accordance with current immunization guidelines prior to initiating TASCENSO ODT.
2.2 Important Administration Instructions Patients who initiate TASCENSO ODT, 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. Patients who are currently treated with another fingolimod product and underwent first-dose monitoring at initiation may be switched to TASCENSO ODT at the same daily dose without a need to repeat first-dose monitoring (unless the previous treatment was discontinued more than 14 days prior) <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 , 2.5 )]</span>. TASCENSO ODT can be taken with or without food. Inform the patient about the following administration instructions for TASCENSO ODT: Store the orally disintegrating tablet (ODT) in the sealed blister until ready to administer. Do not push the ODT through the lidding foil. Use dry hands when opening the blister pack. Peel back the lidding foil from one blister, then push the underside of the foil packet to release the ODT and gently remove the ODT. Take the ODT immediately after opening the blister pack. Place the ODT on the tongue and allow it to dissolve before swallowing. The ODT may be taken with or without water.
2.3 Recommended Dosage In adults and pediatric patients 10 years of age and older weighing more than 40 kg, the recommended dosage of TASCENSO ODT is 0.5 mg orally once-daily. In pediatric patients 10 years of age and older weighing less than or equal to 40 kg, the recommended dosage of TASCENSO ODT is 0.25 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 TASCENSO ODT treatment results in a decrease in heart rate, for which monitoring is recommended <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) , Clinical Pharmacology (12.2) ]</span> . 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 TASCENSO ODT 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 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 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 TASCENSO ODT 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 TASCENSO ODT treatment 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 TASCENSO ODT treatment <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . 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.
Contraindications
TASCENSO ODT is contraindicated in patients who have: in the last 6 months experienced myocardial infarction, unstable angina, stroke, 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 TASCENSO ODT. Observed reactions include rash, urticaria, and angioedema [see Warnings and Precautions (5.14) ]. Concomitant use with other products containing fingolimod Recent myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure. ( 4 ) History of Mobitz Type II 2 nd degree or 3 rd 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 ) Concomitant use with other products containing fingolimod. ( 4 )
Known Adverse Reactions
REACTIONS 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 TASCENSO ODT [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 TASCENSO ODT 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 Cycle Pharmaceuticals Ltd at 1-888-533-1625 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 1212 patients with relapsing forms of multiple sclerosis received fingolimod 0.5 mg capsules. This included 783 patients who received fingolimod 0.5 mg in the 2-year placebo-controlled trials (Studies 1 and 3) and 429 patients who received fingolimod 0.5 mg in the 1-year active-controlled trial (Study 2). The overall exposure in the controlled trials was equivalent to 1716 person-years.
Approximately
1000 patients received at least 2 years of treatment with fingolimod 0.5 mg capsules. In all clinical studies, including uncontrolled extension studies, the exposure to fingolimod 0.5 mg capsules was approximately 4119 person-years. In placebo-controlled trials, the most frequent adverse reactions (incidence ≥ 10% and greater than placebo) for fingolimod 0.5 mg capsules 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 0.5 mg capsules, 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 0.5 mg Capsules at ≥ 1% Higher Rate than for Placebo)
Fingolimod
0.5 mg Capsules N = 783 Placebo N = 773 Adverse Drug Reactions % % 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 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 doses (1.25 mg to 5 mg) higher than recommended for use in MS. Similar events have been reported with fingolimod treatment 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, 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 0.25 mg or 0.5 mg capsules 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 [see Use in Specific Populations (8.4) ] .
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of fingolimod. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Hemolytic anemia and thrombocytopenia Hepatobiliary Disorders: Liver injury <span class="opacity-50 text-xs">[see Warnings and Precautions (5.5) ]</span> Infections: Infections including cryptococcal infections <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span>, human papilloma virus (HPV) infection, including papilloma, dysplasia, warts and HPV-related cancer <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span> , progressive multifocal leukoencephalopathy <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span> Musculoskeletal and connective tissue disorders: Arthralgia, myalgia Nervous System Disorders: Posterior reversible encephalopathy syndrome <span class="opacity-50 text-xs">[see Warnings and Precautions (5.6) ]</span>, seizures, including status epilepticus <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> Neoplasms, Benign, Malignant, and Unspecified (including cysts and polyps): melanoma, Merkel cell carcinoma, cutaneous T- cell lymphoma (including mycosis fungoides), Kaposi’s sarcoma and, squamous cell carcinoma <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.12 )]</span> Skin and Subcutaneous Tissue Disorders: Hypersensitivity <span class="opacity-50 text-xs">[see Warnings and Precautions (5.14) ]</span>
Warnings
AND PRECAUTIONS Bradyarrhythmia and Atrioventricular Blocks : Because of a risk for bradyarrhythmia and AV blocks, monitor during initiation of treatment ( 2.4 , 5.1 ) Infections : TASCENSO ODT may increase the risk. Obtain a complete blood count (CBC) before initiating TASCENSO ODT (i.e., within 6 months). 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 TASCENSO ODT 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 TASCENSO ODT. 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 TASCENSO ODT 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 TASCENSO ODT. ( 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 TASCENSO ODT. ( 5.8 , 8.1 , 8.3 )
Severe
Increase in Disability After Stopping TASCENSO ODT: 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 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 TASCENSO ODT treatment initiation <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . Reduction in Heart Rate After the first dose of TASCENSO ODT, 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 beats per minute (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 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 TASCENSO ODT-induced bradycardia, or experience serious rhythm disturbances after the first dose of TASCENSO ODT. Prior to treatment with TASCENSO ODT, these patients should have a cardiac evaluation by a physician appropriately trained to conduct such evaluation, and if treated with TASCENSO ODT, should be monitored overnight with continuous ECG in a medical facility after the first dose. Since initiation of TASCENSO ODT 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 fingolimod 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 fingolimod dosing, the heart rate returns to baseline within 1 month of chronic treatment. Clinical data indicate effects of TASCENSO ODT 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 TASCENSO ODT 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. 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 is uncertain. Cases of syncope were also reported after the first dose of fingolimod.
5.2 Infections Risk of Infections TASCENSO ODT causes a dose-dependent reduction in peripheral lymphocyte count to 20%-30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. TASCENSO ODT may therefore increase the risk of infections, some serious in nature <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.2) ]</span>. Life-threatening and fatal infections have occurred in association with fingolimod, the active moiety in TASCENSO ODT. Before initiating treatment with TASCENSO ODT, results from a recent CBC (i.e., within 6 months or after discontinuation of prior therapy) should be reviewed. Initiation of treatment with TASCENSO ODT should be delayed in patients with severe active infection until resolution. Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 2 months after discontinuation of TASCENSO ODT, vigilance for infection should be continued throughout this period <span class="opacity-50 text-xs">[see Warnings and Precautions (5.13) ]</span>. In MS placebo-controlled trials in adult patients treated with fingolimod capsules, the overall rate of infections (72%) with fingolimod capsules was similar to placebo. However, bronchitis, herpes zoster, influenza, sinusitis, and pneumonia were more common in fingolimod-treated patients. Serious infections occurred at a rate of 2.3% in the fingolimod group versus 1.6% in the placebo group. In the postmarketing setting, serious infections with opportunistic pathogens including viruses (e.g., John Cunningham virus (JCV), herpes simplex viruses 1 and 2, varicella zoster virus), fungi (e.g., cryptococci), and bacteria (e.g., atypical mycobacteria) have been reported with fingolimod. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and appropriate treatment.
Herpes Viral
Infections In placebo-controlled trials in adult patients treated with fingolimod capsules, the rate of herpetic infections was 9% in patients receiving fingolimod 0.5 mg and 7% on placebo. Two patients died of herpetic infections during controlled trials. One death was due to disseminated primary herpes zoster and the other was to herpes simplex encephalitis. In both cases, the patients were taking a 1.25 mg dose of fingolimod (higher than the recommended 0.5 mg dose) and had received high-dose corticosteroid therapy to treat suspected MS relapses. Serious, life-threatening events of disseminated varicella zoster and herpes simplex infections, including cases of encephalitis and multiorgan failure, have occurred with fingolimod in the postmarketing setting. Include disseminated herpetic infections in the differential diagnosis of patients who are receiving TASCENSO ODT and present with an atypical MS relapse or multiorgan failure. Cases of Kaposi's sarcoma have been reported in patients treated with fingolimod in the postmarketing setting. Kaposi's sarcoma is an angioproliferative disorder that is associated with infection with human herpes virus 8 (HHV-8). Patients with symptoms or signs consistent with Kaposi's sarcoma should be referred for prompt diagnostic evaluation and management.
Cryptococcal Infections
Cryptococcal infections, including cases of fatal cryptococcal meningitis and disseminated cryptococcal infections, have been reported with fingolimod in the postmarketing setting. Cryptococcal infections have generally occurred after approximately 2 years of fingolimod treatment but may occur earlier. The relationship between the risk of cryptococcal infection and the duration of treatment is unknown. Patients with symptoms and signs consistent with a cryptococcal infection should undergo prompt diagnostic evaluation and treatment. Prior and Concomitant Treatment with Antineoplastic, Immunosuppressive, or Immune-Modulating Therapies In clinical studies, patients who received fingolimod capsules did not receive concomitant treatment with antineoplastic, non- corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS. Concomitant use of TASCENSO ODT with any of these therapies, and also with corticosteroids, would be expected to increase the risk of immunosuppression [see Drug Interactions (7.4) ] . When switching to fingolimod from immune-modulating or immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.
Varicella Zoster Virus Antibody Testing/Vaccination
Patients without a healthcare professional confirmed history of chickenpox or without documentation of a full course of vaccination against VZV should be tested for antibodies to VZV before initiating TASCENSO ODT. VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with TASCENSO ODT, following which initiation of treatment with TASCENSO ODT should be postponed for 1 month to allow the full effect of vaccination to occur [see Drug Interactions (7.3) , Use in Specific Populations (8.4) ].
Human Papilloma Virus Infection
Human papilloma virus (HPV) infections, including papilloma, dysplasia, warts, and HPV-related cancer, have been reported in patients treated with fingolimod in the postmarketing setting. Vaccination against HPV should be considered prior to treatment initiation with TASCENSO ODT, taking into account vaccination recommendations. Cancer screening, including Papanicolaou (Pap) test, is recommended as per standard of care for patients using an immunosuppressive therapy.
5.3 Progressive Multifocal Leukoencephalopathy Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients with MS who received fingolimod, the active moiety in TASCENSO ODT, in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in patients who had not been treated previously with natalizumab, which has a known association with PML, were not taking any other immunosuppressive or immunomodulatory medications concomitantly and did not have any ongoing systemic medical conditions resulting in compromised immune system function. Longer treatment duration increases the risk of PML in fingolimod-treated patients; the majority of cases have occurred in patients treated with fingolimod for at least 18 months. At the first sign or symptom suggestive of PML, withhold TASCENSO ODT and perform an appropriate diagnostic evaluation. 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. Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with MS medications associated with PML, including fingolimod. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Lower PML-related mortality and morbidity have been reported following discontinuation of another MS medication associated with PML in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients. If PML is confirmed, treatment with TASCENSO ODT should be discontinued. Immune reconstitution inflammatory syndrome (IRIS) has been reported in patients treated with S1P receptor modulators, including fingolimod, who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.
5.4 Macular Edema S1P receptor modulators, including TASCENSO ODT, have been associated with an increased risk of macular edema. Obtain a baseline evaluation of the fundus, including the macula, near the start of treatment with TASCENSO ODT. Perform an examination of the fundus, including the macula, 3 to 4 months after starting treatment, periodically while on therapy, and any time there is a change in vision. A dose-dependent increase in the risk of macular edema occurred in the fingolimod capsules clinical development program.
In
2-year double-blind, placebo-controlled studies in adult patients with multiple sclerosis, macular edema with or without visual symptoms occurred in 1.5% of patients (11/799) treated with fingolimod 1.25 mg capsules, 0.5% of patients (4/783) treated with fingolimod 0.5 mg capsules, and 0.4% of patients (3/773) treated with placebo. Macular edema occurred predominantly during the first 3 to 4 months of therapy. These clinical trials excluded patients with diabetes mellitus, a known risk factor for macular edema (see below Macular Edema in Patients with History of Uveitis or Diabetes Mellitus ). Symptoms of macular edema included blurred vision and decreased visual acuity. Routine ophthalmological examination detected macular edema in some patients with no visual symptoms. Macular edema generally partially or completely resolved with or without treatment after drug discontinuation. Some patients had residual visual acuity loss even after resolution of macular edema. Macular edema has also been reported in patients taking fingolimod in the postmarketing setting, usually within the first 6 months of treatment. Continuation of TASCENSO ODT in patients who develop macular edema has not been evaluated. Macular edema over an extended period of time (i.e., 6 months) can lead to permanent visual loss. Consider discontinuing TASCENSO ODT if macular edema develops; this decision should include an assessment of the potential benefits and risks for the individual patient. The risk of recurrence after rechallenge has not been evaluated.
Macular
Edema in Patients with History of Uveitis or Diabetes Mellitus Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during TASCENSO ODT therapy. In the combined clinical trial experience in adult patients with all doses of fingolimod capsules, the rate of macular edema was higher in MS patients with a history of uveitis compared to those without a history of uveitis (approximately 20% versus 0.6%, respectively). Fingolimod, the active moiety in TASCENSO ODT, has not been tested in MS patients with diabetes mellitus.
5.5 Liver Injury Clinically significant liver injury has occurred in patients treated with fingolimod in the postmarketing setting. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have occurred as early as ten days after the first dose and have also been reported after prolonged use. Cases of acute liver failure requiring liver transplant have been reported.
In
2-year placebo-controlled clinical trials in adult patients, elevation of liver enzymes (ALT, AST and GGT) to 3-fold the upper limit of normal (ULN) or greater occurred in 14% of patients treated with fingolimod 0.5 mg capsules and 3% of patients on placebo.
Elevations
5-fold the ULN or greater occurred in 4.5% of patients on fingolimod capsules and 1% of patients on placebo. The majority of elevations occurred within 6 to 9 months. In clinical trials, fingolimod capsules were discontinued if the elevation exceeded 5 times the ULN. Serum transaminase levels returned to normal within approximately 2 months after discontinuation of fingolimod capsules. Recurrence of liver transaminase elevations occurred with rechallenge in some patients. Prior to starting treatment with TASCENSO ODT (within 6 months), obtain serum transaminases (ALT and AST) and total bilirubin levels. Obtain transaminase levels and total bilirubin levels periodically until two months after TASCENSO ODT discontinuation. Patients should be monitored for signs and symptoms of any hepatic injury. Measure liver transaminase and bilirubin levels promptly in patients who report symptoms that may indicate liver injury, including new or worsening fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. In this clinical context, if the patient is found to have an alanine aminotransferase (ALT) greater than three times the reference range with serum total bilirubin greater than two times the reference range, treatment with TASCENSO ODT treatment should be interrupted. Treatment should not be resumed if a plausible alternative etiology for the signs and symptoms cannot be established, because these patients are at risk for severe drug-induced liver injury. Because fingolimod exposure is doubled in patients with severe hepatic impairment, these patients should be closely monitored during treatment with TASCENSO ODT, as the risk of adverse reactions is greater [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ].
5.6 Posterior Reversible Encephalopathy Syndrome There have been rare cases of posterior reversible encephalopathy syndrome (PRES) reported in adult patients receiving fingolimod. Symptoms reported included sudden onset of severe headache, altered mental status, visual disturbances, and seizure. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, TASCENSO ODT should be discontinued.
5.7 Respiratory Effects Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) were observed in patients treated with fingolimod, the active moiety in TASCENSO ODT, as early as 1 month after treatment initiation.
In
2-year placebo-controlled trials in adult patients, the reduction from baseline in the percent of predicted values for FEV1 at the time of last assessment on drug was 2.8% for fingolimod 0.5 mg capsules and 1.0% for placebo. For DLCO, the reduction from baseline in percent of predicted values at the time of last assessment on drug was 3.3% for fingolimod 0.5 mg capsules and 0.5% for placebo. The changes in FEV1 appear to be reversible after treatment discontinuation. There is insufficient information to determine the reversibility of the decrease of DLCO after drug discontinuation. In MS placebo-controlled trials in adult patients, dyspnea was reported in 9% of patients receiving fingolimod 0.5 mg capsules and 7% of patients receiving placebo. Several patients discontinued fingolimod capsules because of unexplained dyspnea during the extension (uncontrolled) studies. Fingolimod, the active moiety in TASCENSO ODT, has not been tested in MS patients with compromised respiratory function. Spirometric evaluation of respiratory function and evaluation of DLCO should be performed during therapy with TASCENSO ODT if clinically indicated.
5.8 Fetal Risk Based on findings from animal studies, TASCENSO ODT may cause fetal harm when administered to a pregnant woman. In animal reproduction studies conducted in rats and rabbits, developmental toxicity was observed with administration of fingolimod at doses less than the recommended human dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Because it takes approximately 2 months to eliminate fingolimod from the body, advise females of reproductive potential to use effective contraception to avoid pregnancy during and for 2 months after stopping TASCENSO ODT treatment <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span> .
5.9 Severe Increase in Disability After Stopping TASCENSO ODT Severe increase in disability accompanied by multiple new lesions on MRI has been reported after discontinuation of fingolimod in the postmarketing setting. Patients in most of these reported cases did not return to the functional status they had before stopping fingolimod. The increase in disability generally occurred within 12 weeks after stopping fingolimod but was reported up to 24 weeks after fingolimod discontinuation. Monitor patients for development of severe increase in disability following discontinuation of TASCENSO ODT and begin appropriate treatment as needed. After stopping TASCENSO ODT in the setting of PML, monitor for development of immune reconstitution inflammatory syndrome (PML-IRIS) <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.3 )]</span>.
5.10 Tumefactive Multiple Sclerosis MS relapses with tumefactive demyelinating lesions on imaging have been observed during fingolimod therapy and after fingolimod discontinuation in the postmarketing setting. Most reported cases of tumefactive MS in patients receiving fingolimod have occurred within the first 9 months after fingolimod initiation, but tumefactive MS may occur at any point during treatment. Cases of tumefactive MS have also been reported within the first 4 months after fingolimod discontinuation. Tumefactive MS should be considered when a severe MS relapse occurs during TASCENSO ODT treatment, especially during initiation, or after discontinuation of TASCENSO ODT, prompting imaging evaluation and initiation of appropriate treatment.
5.11 Increased Blood Pressure In adult MS controlled clinical trials, patients treated with fingolimod 0.5 mg capsules had an average increase over placebo of approximately 3 mmHg in systolic pressure, and approximately 2 mmHg in diastolic pressure, first detected after approximately 1 month of fingolimod treatment initiation and persisting with continued treatment. Hypertension was reported as an adverse reaction in 8% of patients on fingolimod 0.5 mg capsules and in 4% of patients on placebo. Blood pressure should be monitored during treatment with TASCENSO ODT.
5.12 Malignancies Cutaneous Malignancies The risk of cutaneous malignancies (including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma) is increased in patients treated with S1P receptor modulators. Use of fingolimod, the active moiety in TASCENSO ODT, has been associated with an increased risk of BCC and melanoma. In two-year placebo-controlled trials in adult patients, the incidence of BCC was 2% in patients on fingolimod 0.5 mg capsules and 1% in patients on placebo <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi’s sarcoma <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span> , and Merkel cell carcinoma have been reported with fingolimod in the postmarketing setting. Skin examinations are recommended prior to or shortly after the start of treatment and periodically thereafter for all patients, particularly those with risk factors for skin cancer. Providers and patients are advised to monitor for suspicious skin lesions. If a suspicious skin lesion is observed, it should be promptly evaluated. As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. Concomitant phototherapy with UV-B radiation or PUVA photochemotherapy is not recommended in patients taking TASCENSO ODT.
Lymphoma
Cases of lymphoma, including both T-cell and B-cell types and CNS lymphoma, have occurred in patients receiving fingolimod, the active moiety in TASCENSO ODT. The reporting rate of non-Hodgkin lymphoma with fingolimod is greater than that expected in the general population adjusted by age, gender, and region. Cutaneous T-cell lymphoma (including mycosis fungoides) has also been reported with fingolimod in the postmarketing setting.
5.13 Immune System Effects Following TASCENSO ODT Discontinuation Fingolimod remains in the blood and has pharmacodynamic effects, including decreased lymphocyte counts, for up to 2 months following the last dose of TASCENSO ODT. Lymphocyte counts generally return to the normal range within 1 to 2 months of stopping therapy <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.2) ]</span>. Because of the continuing pharmacodynamic effects of fingolimod, initiating other drugs during this period warrants the same considerations needed for concomitant administration (e.g., risk of additive immunosuppressant effects) <span class="opacity-50 text-xs">[see Drug Interactions (7.4) ]</span>.
5.14 Hypersensitivity Reactions Hypersensitivity reactions, including rash, urticaria, and angioedema have been reported with fingolimod in the postmarketing setting. TASCENSO ODT is contraindicated in patients with history of hypersensitivity to fingolimod or any of its excipients <span class="opacity-50 text-xs">[see Contraindications (4)]</span>.
Drug Interactions
INTERACTIONS Systemic Ketoconazole : Monitor during concomitant use. ( 7.2 , 12.3 ) Vaccines : Avoid live attenuated vaccines during, and for 2 months after stopping TASCENSO ODT treatment. ( 5.3 , 7.3 )