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Drug overview for GILENYA (fingolimod hcl):
Generic name: FINGOLIMOD HCL (fin-GOL-i-mod)
Drug class: Multiple Sclerosis Agents, General
Therapeutic class: Multiple Sclerosis Agents
Fingolimod hydrochloride, a sphingosine 1-phosphate (S1P) receptor modulator, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS).
No enhanced Uses information available for this drug.
Generic name: FINGOLIMOD HCL (fin-GOL-i-mod)
Drug class: Multiple Sclerosis Agents, General
Therapeutic class: Multiple Sclerosis Agents
Fingolimod hydrochloride, a sphingosine 1-phosphate (S1P) receptor modulator, has immunomodulatory and disease-modifying activity in multiple sclerosis (MS).
No enhanced Uses information available for this drug.
DRUG IMAGES
GILENYA 0.5 MG CAPSULE
The following indications for GILENYA (fingolimod hcl) have been approved by the FDA:
Indications:
Relapsing form of multiple sclerosis
Secondary progressive multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
Indications:
Relapsing form of multiple sclerosis
Secondary progressive multiple sclerosis
Professional Synonyms:
Multiple sclerosis, relapsing form
The following dosing information is available for GILENYA (fingolimod hcl):
Initiation of fingolimod therapy results in a decrease in heart rate. After the first dose, the heart rate decrease starts within an hour and the nadir on day 1 generally occurs within about 6 hours; however, the nadir can be observed up to 24 hours after the first dose in some patients.
First-dose monitoring is recommended whenever fingolimod therapy is initiated or reinitiated (after discontinuance for more than 14 days), or when dosage is increased (in pediatric patients). The first dose of fingolimod should be administered in a setting in which resources to appropriately manage symptomatic bradycardia are available. To assess patient response to the first dose, all patients should be observed for at least 6 hours for signs and symptoms of bradycardia with hourly pulse and blood pressure measurements.
An electrocardiogram (ECG) should be obtained in all patients prior to the first dose and at the end of the observation period.
Additional observation (i.e., beyond 6 hours) should be instituted until the finding has resolved in the following situations: heart rate 6 hours post-dose is less than 45 beats per minute (in adults), less than 55 beats per minute (in pediatric patients 12 years of age or older), or less than 60 beats per minute (in pediatric patients 10-11 years of age); heart rate 6 hours post-dose is at the lowest value suggesting that the maximum pharmacodynamic effect on the heart may not have occurred; or ECG 6 hours post-dose shows new-onset second-degree or higher atrioventricular (AV) block. Patients at their lowest post-dose heart rate at the end of the observation period should be monitored until their heart rate increases.
If post-dose symptomatic bradycardia occurs, appropriate management and continuous ECG monitoring should be initiated and observation continued until the symptoms have resolved. If pharmacologic intervention is required for symptomatic bradycardia, continuous overnight ECG monitoring in a medical facility should be instituted and the first-dose monitoring strategy should be repeated after the second dose of fingolimod.
Patients with certain 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 fingolimod-induced bradycardia or experience serious rhythm disturbances after the first dose of the drug. Such patients should have a cardiac evaluation by an appropriately trained clinician prior to initiating fingolimod therapy; if a decision is made to initiate therapy, the patient should be monitored overnight with continuous ECG monitoring in a medical facility.
Because initiation of fingolimod therapy results in a decreased heart rate and may prolong the QT interval, the following patients should be monitored overnight with continuous ECG monitoring in a medical facility: patients with a prolonged corrected QT (QTc) interval (i.e., exceeding 450 msec in adult and pediatric males; exceeding 470 msec in adult females; or exceeding 460 msec in pediatric females) before dosing or during the 6-hour observation period, patients at additional risk for QT prolongation (e.g., those with hypokalemia, hypomagnesemia, or congenital long QT syndrome), or patients receiving concurrent therapy with QT-prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, certain antipsychotic agents (e.g., chlorpromazine, haloperidol, olanzapine, pimozide, quetiapine, risperidone, thioridazine, ziprasidone), erythromycin, methadone).
Because of the risk of severe bradycardia or heart block, patients receiving concurrent therapy with drugs that slow heart rate or AV conduction (e.g., beta-adrenergic blocking agents, digoxin, heart rate-lowering calcium-channel blocking agents (diltiazem or verapamil)) who are not able to switch to other drugs without these effects should receive continuous overnight ECG monitoring after the first dose of fingolimod.
Dosage of fingolimod hydrochloride is expressed in terms of fingolimod.
The recommended dosage of fingolimod for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive disease in pediatric patients >=10 years of age is 0.5 mg orally once daily in those weighing >40 kg and 0.25 mg once daily in those weighing <=40 kg.
Dosages higher than 0.5 mg daily are associated with a greater incidence of adverse reactions without additional benefit.
The recommended dosage of fingolimod for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive disease in adults is 0.5 mg orally once daily. Dosages higher than 0.5 mg daily are associated with a greater incidence of adverse reactions without additional benefit.
First-dose monitoring is recommended whenever fingolimod therapy is initiated or reinitiated (after discontinuance for more than 14 days), or when dosage is increased (in pediatric patients). The first dose of fingolimod should be administered in a setting in which resources to appropriately manage symptomatic bradycardia are available. To assess patient response to the first dose, all patients should be observed for at least 6 hours for signs and symptoms of bradycardia with hourly pulse and blood pressure measurements.
An electrocardiogram (ECG) should be obtained in all patients prior to the first dose and at the end of the observation period.
Additional observation (i.e., beyond 6 hours) should be instituted until the finding has resolved in the following situations: heart rate 6 hours post-dose is less than 45 beats per minute (in adults), less than 55 beats per minute (in pediatric patients 12 years of age or older), or less than 60 beats per minute (in pediatric patients 10-11 years of age); heart rate 6 hours post-dose is at the lowest value suggesting that the maximum pharmacodynamic effect on the heart may not have occurred; or ECG 6 hours post-dose shows new-onset second-degree or higher atrioventricular (AV) block. Patients at their lowest post-dose heart rate at the end of the observation period should be monitored until their heart rate increases.
If post-dose symptomatic bradycardia occurs, appropriate management and continuous ECG monitoring should be initiated and observation continued until the symptoms have resolved. If pharmacologic intervention is required for symptomatic bradycardia, continuous overnight ECG monitoring in a medical facility should be instituted and the first-dose monitoring strategy should be repeated after the second dose of fingolimod.
Patients with certain 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 fingolimod-induced bradycardia or experience serious rhythm disturbances after the first dose of the drug. Such patients should have a cardiac evaluation by an appropriately trained clinician prior to initiating fingolimod therapy; if a decision is made to initiate therapy, the patient should be monitored overnight with continuous ECG monitoring in a medical facility.
Because initiation of fingolimod therapy results in a decreased heart rate and may prolong the QT interval, the following patients should be monitored overnight with continuous ECG monitoring in a medical facility: patients with a prolonged corrected QT (QTc) interval (i.e., exceeding 450 msec in adult and pediatric males; exceeding 470 msec in adult females; or exceeding 460 msec in pediatric females) before dosing or during the 6-hour observation period, patients at additional risk for QT prolongation (e.g., those with hypokalemia, hypomagnesemia, or congenital long QT syndrome), or patients receiving concurrent therapy with QT-prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, certain antipsychotic agents (e.g., chlorpromazine, haloperidol, olanzapine, pimozide, quetiapine, risperidone, thioridazine, ziprasidone), erythromycin, methadone).
Because of the risk of severe bradycardia or heart block, patients receiving concurrent therapy with drugs that slow heart rate or AV conduction (e.g., beta-adrenergic blocking agents, digoxin, heart rate-lowering calcium-channel blocking agents (diltiazem or verapamil)) who are not able to switch to other drugs without these effects should receive continuous overnight ECG monitoring after the first dose of fingolimod.
Dosage of fingolimod hydrochloride is expressed in terms of fingolimod.
The recommended dosage of fingolimod for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive disease in pediatric patients >=10 years of age is 0.5 mg orally once daily in those weighing >40 kg and 0.25 mg once daily in those weighing <=40 kg.
Dosages higher than 0.5 mg daily are associated with a greater incidence of adverse reactions without additional benefit.
The recommended dosage of fingolimod for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive disease in adults is 0.5 mg orally once daily. Dosages higher than 0.5 mg daily are associated with a greater incidence of adverse reactions without additional benefit.
Administer fingolimod orally once daily without regard to meals. Take fingolimod orally disintegrating tablets immediately after opening the blister pack; do not store the orally disintegrating tablet outside the blister pack for future use. The manufacturer recommends using caution when switching patients from drugs with prolonged immune effects (e.g., natalizumab, mitoxantrone, teriflunomide) to fingolimod.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| GILENYA 0.5 MG CAPSULE | Maintenance | Adults take 1 capsule (0.5 mg) by oral route once daily |
| GILENYA 0.25 MG CAPSULE | Maintenance | Adults take 2 capsules (0.5 mg) by oral route once daily |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| FINGOLIMOD 0.5 MG CAPSULE | Maintenance | Adults take 1 capsule (0.5 mg) by oral route once daily |
The following drug interaction information is available for GILENYA (fingolimod hcl):
There are 5 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Efalizumab; Natalizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV). PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000. PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7) DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10) |
TYSABRI |
| Live Vaccines; Live BCG/Selected Immunosuppressive Agents SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1) CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2) PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency. PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1) |
ACAM2000 (NATIONAL STOCKPILE), ADENOVIRUS TYPE 4, ADENOVIRUS TYPE 4 AND TYPE 7, ADENOVIRUS TYPE 7, BCG (TICE STRAIN), BCG VACCINE (TICE STRAIN), DENGVAXIA, ERVEBO (NATIONAL STOCKPILE), FLUMIST 2025-2026, FLUMIST HOME 2025-2026, IXCHIQ, M-M-R II VACCINE, PRIORIX, PROQUAD, ROTARIX, ROTATEQ, STAMARIL, VARIVAX VACCINE, VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE, VIVOTIF, YF-VAX |
| Fingolimod/Class IA and III Antiarrhythmic Agents SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Initiation of fingolimod has a negative chronotropic effect leading to a mean decrease in heart rate of 13 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block.(1-4) CLINICAL EFFECTS: The heart rate lowering effect of fingolimod is biphasic with an initial decrease usually within 6 hours, followed by a second decrease 12 to 24 hours after the first dose. Symptomatic bradycardia and heart block, including third degree block, have been observed. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsades de pointes. The cause of death in a patient who died within 24 hour after taking the first dose of fingolimod was not conclusive, however a link to fingolimod could not be ruled out. PREDISPOSING FACTORS: Pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, history of torsades de pointes, congenital long QT syndrome, stroke, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to fingolimod initiation, factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia, bradycardia, female gender, advanced age), or concomitant treatment with Class IA or III agents may increase risk for cardiovascular toxicity due to fingolimod. Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(5) PATIENT MANAGEMENT: US, Canada and UK manufacturer information states Class Ia or Class III antiarrhythmics are contraindicated and should not be co-administered with fingolimod.(1-4) If concurrent therapy is deemed medically necessary, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(1,2) Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(1,2) Antiarrhythmic agents linked to this monograph are disopyramide, procainamide, quinidine, amiodarone, dofetilide, dronedarone, ibutilide and sotalol. |
AMIODARONE HCL, AMIODARONE HCL-D5W, BETAPACE, BETAPACE AF, CORVERT, DISOPYRAMIDE PHOSPHATE, DOFETILIDE, IBUTILIDE FUMARATE, MULTAQ, NEXTERONE, NORPACE, NORPACE CR, NUEDEXTA, PACERONE, PROCAINAMIDE HCL, QUINIDINE GLUCONATE, QUINIDINE SULFATE, SOTALOL, SOTALOL AF, SOTALOL HCL, SOTYLIZE, TIKOSYN |
| Talimogene laherparepvec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus.(1) CLINICAL EFFECTS: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Talimogene laherparepvec is contraindicated in immunosuppressed patients.(1) The magnitude of immunocompromise and associated risks due to immunosuppressant drugs should be determined by a physician. DISCUSSION: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) |
IMLYGIC |
| Nadofaragene Firadenovec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nadofaragene firadenovec may contain low levels of replication-competent adenovirus.(1) CLINICAL EFFECTS: Concurrent use of nadofaragene firadenovec in patients receiving immunosuppressive therapy may cause disseminated adenovirus infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Individuals who are immunosuppressed or immune-deficient should not receive nadofaragene firadenovec.(1) DISCUSSION: Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy but may contain low levels of replication-competent adenovirus. Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection.(1) |
ADSTILADRIN |
There are 4 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Fingolimod/Beta-Blockers; AV Node Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Initiation of fingolimod has a negative chronotropic effect leading to a mean decrease in heart rate of 13 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block. Beta-blockers or agents which slow AV node conduction further increase the risk for symptomatic bradycardia or heart block. CLINICAL EFFECTS: The heart rate lowering effect of fingolimod is biphasic with an initial decrease usually within 6 hours, followed by a second decrease 12 to 24 hours after the first dose. Symptomatic bradycardia and heart block have been observed. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsade de pointes. The cause of death in a patient who died within 24 hour after taking the first dose of fingolimod was not conclusive; however a link to fingolimod or a drug interaction with fingolimod could not be ruled out. Beta-Blockers linked to this monograph are: atenolol, betaxolol, bisoprolol, carvedilol, esmolol, landiolol, labetalol, metoprolol, nadolol, nebivolol, propranolol and timolol. AV Node Blocking agents are:digoxin, diltiazem, flecainide, ivabradine, propafenone and verapamil. PREDISPOSING FACTORS: Pre-existing cardiovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, history of torsades de pointes, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to fingolimod initiation, or factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia, bradycardia, female gender, or advanced age) may increase risk for cardiovascular toxicity due to fingolimod. Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(5) PATIENT MANAGEMENT: Fingolimod is contraindicated in patients with Class III/IV heart failure or in patients who have experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA) or decompensated heart failure within the past six months.(1) Patients with pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, or a prolonged QTc interval prior to fingolimod initiation should receive cardiologist consultation to evaluate the risks of fingolimod therapy. Patients receiving agents linked to this monograph should have their physician evaluate the possibility of a switch to agents which do not slow heart rate or cardiac conduction. If fingolimod is initiated, the patient should stay overnight in a medical facility with continuous ECG monitoring after the first dose. Correct hypokalemia or hypomagnesemia prior to starting fingolimod. US monitoring recommendations in addition to continuous ECG with overnight monitoring: Check blood pressure hourly. If heart rate (HR) is < 45 beats per minute (BPM) or if the ECG shows new onset of second degree or higher AV block at the end of the monitoring period, then monitoring should continue until the finding has resolved. If patient requires treatment for symptomatic bradycardia, the first dose monitoring strategy should be repeated for the second dose of fingolimod. If, within the first two weeks of treatment one or more fingolimod doses is missed, then first dose procedures are recommended upon resumption. If during weeks 3 and 4 of fingolimod treatment dose is interrupted more than 7 days, then first dose procedures are recommended upon resumption. United Kingdom recommendations(3): Obtain a 12-lead ECG prior to initiating fingolimod therapy. Consult a cardiologist for pretreatment risk-benefit assessment if patient has a resting heart rate less than 55 bpm, history of syncope, second degree or greater AV block, sick-sinus syndrome, concurrent therapy with beta-blockers, Class Ia, or Class III antiarrhythmics, heart failure or other significant cardiovascular disease. Perform continuous ECG monitoring, measure blood pressure and heart rate every hour, and perform a 12-lead ECG 6 hours after the first dose. Monitoring should be extended beyond 6 hours if symptomatic bradycardia or new onset of second degree AV block, Mobitz Type II or third degree AV block has occurred at any time during the monitoring period. If heart rate 6 hours after the first dose is less than 40 bpm, has decreased more than 20 bpm compared with baseline, or if a new onset second degree AV block, Mobitz Type I (Wenckebach) persists, then monitoring should also be continued. If fingolimod treatment is discontinued for more than two weeks, the effects on heart rate and conduction could recur. Thus, first dose monitoring precautions should be followed upon reintroduction of fingolimod. DISCUSSION: After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(1,2) Diurnal variation in heart rate and response to exercise are not affected by fingolimod treatment.(2) In a manufacturer sponsored study, fingolimod and atenolol 50 mg daily lowered heart rate 15% more than fingolimod alone. However, additional heart rate lowering was not seen with the combination of extended release diltiazem and fingolimod compared with fingolimod alone.(1) |
ACEBUTOLOL HCL, ATENOLOL, ATENOLOL-CHLORTHALIDONE, BETAXOLOL HCL, BISOPROLOL FUMARATE, BISOPROLOL-HYDROCHLOROTHIAZIDE, BREVIBLOC, BYSTOLIC, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CARVEDILOL, CARVEDILOL ER, COREG, COREG CR, CORLANOR, DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, ESMOLOL HCL, ESMOLOL HCL-SODIUM CHLORIDE, ESMOLOL HCL-WATER, FLECAINIDE ACETATE, HEMANGEOL, INDERAL LA, INDERAL XL, INNOPRAN XL, IVABRADINE HCL, KAPSPARGO SPRINKLE, LABETALOL HCL, LABETALOL HCL-WATER, LANOXIN, LANOXIN PEDIATRIC, LOPRESSOR, MATZIM LA, METOPROLOL SUCCINATE, METOPROLOL TARTRATE, METOPROLOL-HYDROCHLOROTHIAZIDE, NADOLOL, NEBIVOLOL HCL, PINDOLOL, PROPAFENONE HCL, PROPAFENONE HCL ER, PROPRANOLOL HCL, PROPRANOLOL HCL ER, PROPRANOLOL-HYDROCHLOROTHIAZID, RAPIBLYK, TENORETIC 100, TENORETIC 50, TENORMIN, TIADYLT ER, TIAZAC, TIMOLOL MALEATE, TOPROL XL, TRANDOLAPRIL-VERAPAMIL ER, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR |
| Fingolimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - 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. 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.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3) |
ABECMA, ABRAXANE, ABRILADA(CF), ABRILADA(CF) PEN, ABRILADA(CF) PEN (2 PACK), ACTEMRA, ACTEMRA ACTPEN, ACTIMMUNE, ADALIMUMAB-AACF(CF), ADALIMUMAB-AACF(CF) (2 PK), ADALIMUMAB-AACF(CF) PEN (2 PK), ADALIMUMAB-AACF(CF) PEN CROHNS, ADALIMUMAB-AACF(CF) PEN PS-UV, ADALIMUMAB-AATY(CF) (2 PACK), ADALIMUMAB-AATY(CF) (2 PK), ADALIMUMAB-AATY(CF) AI CROHNS, ADALIMUMAB-AATY(CF) AUTOINJ(2), ADALIMUMAB-AATY(CF) AUTOINJECT, ADALIMUMAB-ADAZ(CF), ADALIMUMAB-ADAZ(CF) PEN, ADALIMUMAB-ADBM(CF), ADALIMUMAB-ADBM(CF) PEN, ADALIMUMAB-ADBM(CF) PEN CROHNS, ADALIMUMAB-ADBM(CF) PEN PS-UV, ADALIMUMAB-ADBM(CF)PEN, ADALIMUMAB-FKJP(CF), ADALIMUMAB-FKJP(CF) PEN, ADALIMUMAB-RYVK(CF), ADALIMUMAB-RYVK(CF) AUTOINJECT, ADCETRIS, ADRIAMYCIN, ADRUCIL, AFINITOR, AFINITOR DISPERZ, AGAMREE, AKEEGA, ALFERON N, ALIMTA, ALIQOPA, ALKERAN, ALKINDI SPRINKLE, ALUNBRIG, ALYMSYS, AMJEVITA(CF), AMJEVITA(CF) AUTOINJECTOR, AMTAGVI, ANUCORT-HC, ANUSOL-HC, ARAVA, ARCALYST, ARRANON, ARZERRA, ASPARLAS, AUBAGIO, AUCATZYL, AUGTYRO, AVASTIN, AVGEMSI, AVONEX, AVONEX (4 PACK), AVONEX PEN, AVONEX PEN (4 PACK), AVSOLA, AXTLE, AZACITIDINE, AZASAN, AZATHIOPRINE, AZATHIOPRINE SODIUM, AZELAIC ACID, BAFIERTAM, BAVENCIO, BECLOMETHASONE DIPROPIONATE, BELEODAQ, BELRAPZO, BENDAMUSTINE HCL, BENDEKA, BESREMI, BETA 1, BETALOAN SUIK, BETAMETHASONE ACETATE MICRO, BETAMETHASONE ACETATE-SOD PHOS, BETAMETHASONE DIPROPIONATE, BETAMETHASONE SOD PHOS-ACETATE, BETAMETHASONE SOD PHOS-WATER, BETAMETHASONE SODIUM PHOSPHATE, BETAMETHASONE VALERATE, BETASERON, BEXAROTENE, BICNU, BIMZELX, BIMZELX AUTOINJECTOR, BLEOMYCIN SULFATE, BLINCYTO, BORTEZOMIB, BORUZU, BOSULIF, BREYANZI, BREYANZI CD4 COMPONENT, BREYANZI CD8 COMPONENT, BRIUMVI, BRUKINSA, BSP 0820, BUDESONIDE, BUDESONIDE DR, BUDESONIDE EC, BUDESONIDE ER, BUDESONIDE MICRONIZED, BUPIVACAINE-DEXAMETH-EPINEPHRN, BUSULFAN, BUSULFEX, CAELYX, CALQUENCE, CAMPATH, CAMPTOSAR, CAPECITABINE, CARBOPLATIN, CARMUSTINE, CARVYKTI, CELESTONE, CELLCEPT, CHLORAMBUCIL, CIBINQO, CIMZIA, CIMZIA (2 PACK), CISPLATIN, CLADRIBINE, CLOBETASOL PROPIONATE MICRO, CLOFARABINE, COLUMVI, COPAXONE, COPIKTRA, CORTEF, CORTISONE ACETATE, COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN, COSMEGEN, CYCLOPHOSPHAMIDE, CYCLOPHOSPHAMIDE MONOHYDRATE, CYCLOSPORINE, CYCLOSPORINE MODIFIED, CYLTEZO(CF), CYLTEZO(CF) PEN, CYLTEZO(CF) PEN CROHN'S-UC-HS, CYLTEZO(CF) PEN PSORIASIS-UV, CYTARABINE, DACARBAZINE, DACTINOMYCIN, DANYELZA, DARAPRIM, DARZALEX, DARZALEX FASPRO, DAUNORUBICIN HCL, DECITABINE, DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), DEFLAZACORT, DEPO-MEDROL, DESONIDE MICRONIZED, DESOXIMETASONE, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DEXRAZOXANE, DIMETHYL FUMARATE, DMT SUIK, DOCETAXEL, DOCIVYX, DOUBLEDEX, DOXIL, DOXORUBICIN HCL, DOXORUBICIN HCL LIPOSOME, DROXIA, EFLORNITHINE HCL, ELAHERE, ELREXFIO, EMFLAZA, ENBREL, ENBREL MINI, ENBREL SURECLICK, ENHERTU, ENSPRYNG, ENTYVIO, ENTYVIO PEN, EOHILIA, EPKINLY, ERBITUX, ERLOTINIB HCL, ERWINASE, ETOPOPHOS, ETOPOSIDE, EVEROLIMUS, EVOMELA, FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY), FLOXURIDINE, FLUDARABINE PHOSPHATE, FLUNISOLIDE, FLUOCINOLONE ACETONIDE, FLUOCINOLONE ACETONIDE MICRO, FLUOCINONIDE MICRONIZED, FLUOROURACIL, FLUTICASONE PROPIONATE, FLUTICASONE PROPIONATE MICRO, FOLOTYN, FRINDOVYX, FYARRO, GAMIFANT, GAVRETO, GAZYVA, GEFITINIB, GEMCITABINE HCL, GENGRAF, GLATIRAMER ACETATE, GLATOPA, GLEEVEC, GLEOSTINE, GLIADEL, GRAFAPEX, HADLIMA, HADLIMA PUSHTOUCH, HADLIMA(CF), HADLIMA(CF) PUSHTOUCH, HEMADY, HEMMOREX-HC, HEPZATO, HERCEPTIN, HERCEPTIN HYLECTA, HERCESSI, HERZUMA, HEXATRIONE, HICON, HULIO(CF), HULIO(CF) PEN, HUMIRA, HUMIRA PEN, HUMIRA(CF), HUMIRA(CF) PEN, HUMIRA(CF) PEN CROHN'S-UC-HS, HUMIRA(CF) PEN PSOR-UV-ADOL HS, HYCAMTIN, HYDREA, HYDROCORTISONE, HYDROCORTISONE ACETATE, HYDROCORTISONE SOD SUCCINATE, HYDROXYUREA, HYRIMOZ(CF), HYRIMOZ(CF) PEDIATRIC CROHN'S, HYRIMOZ(CF) PEN, HYRIMOZ(CF) PEN CROHN-UC START, HYRIMOZ(CF) PEN PSORIASIS, IBRANCE, ICLUSIG, IDAMYCIN PFS, IDARUBICIN HCL, IFEX, IFOSFAMIDE, ILARIS, IMATINIB MESYLATE, IMBRUVICA, IMDELLTRA, IMFINZI, IMKELDI, IMULDOSA, IMURAN, INFLECTRA, INFLIXIMAB, INFUGEM, INQOVI, INREBIC, IRESSA, IRINOTECAN HCL, IVRA, IWILFIN, IXEMPRA, JAKAFI, JAYPIRCA, JEMPERLI, JEVTANA, JOENJA, JYLAMVO, KADCYLA, KANJINTI, KEMOPLAT, KENALOG-10, KENALOG-40, KENALOG-80, KEVZARA, KEYTRUDA, KHINDIVI, KINERET, KYMRIAH, LEFLUNICLO, LEFLUNOMIDE, LENALIDOMIDE, LEQSELVI, LEUKERAN, LIDOCIDEX-I, LITFULO, LONSURF, LOQTORZI, LUNSUMIO, LUTATHERA, LYNOZYFIC, LYNPARZA, MAS CARE-PAK, MATULANE, MECHLORETHAMINE HCL, MEDROL, MEDROLOAN II SUIK, MEDROLOAN SUIK, MEKINIST, MEKTOVI, MELPHALAN HCL, MERCAPTOPURINE, METHOTREXATE, METHOTREXATE SODIUM, METHYLPREDNISOLONE, METHYLPREDNISOLONE AC MICRO, METHYLPREDNISOLONE ACETATE, METHYLPREDNISOLONE SODIUM SUCC, MILLIPRED, MILLIPRED DP, MITOMYCIN, MITOXANTRONE HCL, MOMETASONE FUROATE, MONJUVI, MUTAMYCIN, MVASI, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN, MYLERAN, MYLOTARG, NELARABINE, NEORAL, NIPENT, NULOJIX, OGIVRI, OJJAARA, OLUMIANT, ONCASPAR, ONIVYDE, ONTRUZANT, ONUREG, OPDIVO, OPDIVO QVANTIG, OPDUALAG, ORAPRED ODT, ORENCIA, ORENCIA CLICKJECT, ORTIKOS, OTREXUP, OTULFI, PACLITAXEL, PACLITAXEL PROTEIN-BOUND, PADCEV, PARAPLATIN, PEDIAPRED, PEGASYS, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU, PERJETA, PHESGO, PHOTOFRIN, PLEGRIDY, PLEGRIDY PEN, PLUVICTO, POLIVY, POMALYST, POTELIGEO, PRALATREXATE, PREDNISOLONE, PREDNISOLONE ACETATE MICRONIZE, PREDNISOLONE MICRONIZED, PREDNISOLONE SODIUM PHOS ODT, PREDNISOLONE SODIUM PHOSPHATE, PREDNISONE, PREDNISONE INTENSOL, PREDNISONE MICRONIZED, PRO-C-DURE 5, PRO-C-DURE 6, PROCARBAZINE HCL, PROCTOCORT, PROLEUKIN, PROVENGE, PURIXAN, PYRIMETHAMINE, PYZCHIVA, RASUVO, RAYOS, REBIF, REBIF REBIDOSE, REMICADE, RENFLEXIS, REVLIMID, REZUROCK, RIABNI, RINVOQ, RINVOQ LQ, RITUXAN, RITUXAN HYCELA, RUXIENCE, RYLAZE, RYTELO, SANDIMMUNE, SARCLISA, SCEMBLIX, SELARSDI, SIKLOS, SIMLANDI(CF), SIMLANDI(CF) AUTOINJECTOR, SIMPONI, SIMPONI ARIA, SIMULECT, SIROLIMUS, SODIUM IODIDE I-123, SODIUM IODIDE I-131, SOLU-CORTEF, SOLU-MEDROL, SOTYKTU, STELARA, STEQEYMA, STRONTIUM-89 CHLORIDE, TABLOID, TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE, TALVEY, TALZENNA, TAPERDEX, TARGRETIN, TARPEYO, TECARTUS, TECELRA, TECENTRIQ, TECENTRIQ HYBREZA, TECFIDERA, TECVAYLI, TEMODAR, TEMOZOLOMIDE, TEMSIROLIMUS, TEPADINA, TEPYLUTE, TERIFLUNOMIDE, TEVIMBRA, THIOTEPA, TOFACITINIB CITRATE, TOFIDENCE, TOPOTECAN HCL, TORISEL, TORPENZ, TRAMETINIB, TRAZIMERA, TREANDA, TRETINOIN, TREXALL, TRIAMCINOLONE, TRIAMCINOLONE ACETONIDE, TRIAMCINOLONE DIACETATE, TRIAMCINOLONE DIACETATE MICRO, TRILOAN II SUIK, TRILOAN SUIK, TRODELVY, TRUQAP, TRUXIMA, TYENNE, TYENNE AUTOINJECTOR, TZIELD, UCERIS, UNITUXIN, UPLIZNA, USTEKINUMAB, USTEKINUMAB-AEKN, USTEKINUMAB-TTWE, UVADEX, VECTIBIX, VEGZELMA, VELCADE, VELSIPITY, VENCLEXTA, VENCLEXTA STARTING PACK, VERIPRED 20, VERZENIO, VIDAZA, VINBLASTINE SULFATE, VINCASAR PFS, VINCRISTINE SULFATE, VINORELBINE TARTRATE, VITRAKVI, VIVIMUSTA, VYXEOS, WEZLANA, XATMEP, XELJANZ, XELJANZ XR, XELODA, XOFIGO, XPOVIO, XROMI, YESCARTA, YESINTEK, YONDELIS, YUFLYMA(CF) (2 PACK), YUFLYMA(CF) AI CROHN'S-UC-HS, YUFLYMA(CF) AUTOINJECT (2 PCK), YUFLYMA(CF) AUTOINJECTOR, YUSIMRY(CF) PEN, ZANOSAR, ZCORT, ZEJULA, ZEPZELCA, ZEVALIN, ZILRETTA, ZIRABEV, ZOLINZA, ZORTRESS, ZYDELIG, ZYMFENTRA, ZYMFENTRA (2 PACK), ZYMFENTRA PEN (2 PACK), ZYNLONTA, ZYNYZ |
| Fingolimod/Immunosuppressives; Immunomodulators that Prolong QT SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) Initiation of fingolimod has a negative chronotropic effect leading to a mean decrease in heart rate of 13 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3) The heart rate lowering effect of fingolimod is biphasic with an initial decrease usually within 6 hours, followed by a second decrease 12 to 24 hours after the first dose. Symptomatic bradycardia and heart block, including third degree block, have been observed. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsades de pointes. There is no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment.(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications may increase the risk from this interaction. Pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to fingolimod initiation, factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia), or concomitant treatment with QT prolonging agents may increase risk for cardiovascular toxicity due to fingolimod. The risk of QT prolongation or torsades de pointes may also be increased in patients with a history of torsades de pointes, hypocalcemia, bradycardia, female gender, or advanced age.(4) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(4) PATIENT MANAGEMENT: Recommendations for managing this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - 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. 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.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK summary of product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to fingolimod, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) Patients receiving concurrent treatment with a QT prolonging agent at the time fingolimod is initiated or resumed should be monitored overnight with continuous ECG monitoring in a medical facility. Consult the prescribing information for recommendations regarding cardiac monitoring.(1) Correct hypokalemia or hypomagnesemia prior to starting fingolimod. DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3) After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(1,2) In a thorough QT interval study of doses of 1.25 or 2.5 mg fingolimod at steady-state, when a negative chronotropic effect of fingolimod was still present, fingolimod treatment resulted in a prolongation of QTc, with the upper boundary of the 90% confidence interval (CI) of 14.0 msec. The cause of death in a patient who died within 24 hours after taking the first dose of fingolimod was not conclusive; however a link to fingolimod or a drug interaction with fingolimod could not be ruled out.(1) |
ARSENIC TRIOXIDE, ASTAGRAF XL, BESPONSA, BRAFTOVI, DANZITEN, DASATINIB, DAURISMO, ELLENCE, ENVARSUS XR, EPIRUBICIN HCL, FARYDAK, ISTODAX, KISQALI, LAPATINIB, NILOTINIB HCL, NILOTINIB TARTRATE, OXALIPLATIN, PAZOPANIB HCL, PROGRAF, QUALAQUIN, QUININE HCL, QUININE SULFATE, REVUFORJ, ROMIDEPSIN, RUBRACA, RYDAPT, SPRYCEL, SUNITINIB MALATE, SUTENT, TACROLIMUS, TACROLIMUS XL, TASIGNA, TRISENOX, TYKERB, VANFLYTA, VOTRIENT, XALKORI, ZOKINVY |
| Clozapine/Fingolimod SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of clozapine with other agents that prolong the QTc interval may result in additive effects on the QTc interval.(1) Initiation of fingolimod has a negative chronotropic effect and may cause bradycardia, which may increase the risk of QT prolongation.(2-4) Clozapine and concurrent use with other myelosuppressive agents, including fingolimod, may be associated with additive risk of neutropenia or agranulocytosis.(1) CLINICAL EFFECTS: Concurrent use of clozapine with agents that prolong the QTc interval may result in potentially life-threatening cardiac arrhythmias.(1) Fingolimod causes a biphasic lowering of the heart rate (HR), initially within 6 hours, and then at 12-24 hours after the first dose. Symptomatic bradycardia and heart block, including third degree block, have been observed. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsade de pointes. There is no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment.(2-4) Moderate neutropenia may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). Fingolimod therapy may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of fingolimod. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(5) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(5) Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia.(1) PATIENT MANAGEMENT: Approach the concurrent use of clozapine and other agents that prolong the QTc interval with caution.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If a patient stabilized on clozapine therapy requires treatment with other myelosuppressive agents the clozapine prescriber should consult with the prescriber of the myelosuppressive agent to discuss treatment and monitoring options. More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing. For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(1) Patients receiving concurrent treatment with a QT prolonging agent at the time fingolimod is initiated or resumed should be referred to a cardiologist. Consult the prescribing information for recommendations regarding cardiac monitoring.(2-4) DISCUSSION: Treatment with clozapine has been associated with QT prolongation as well as ventricular arrhythmia, torsades de pointes, cardiac arrest, and sudden death.(1) Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1,7) After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(2,3) In a thorough QT interval study of doses of 1.25 or 2.5 mg fingolimod at steady-state, when a negative chronotropic effect of fingolimod was still present, fingolimod treatment resulted in a prolongation of QTc, with the upper boundary of the 90% confidence interval (CI) of 14.0 msec. The cause of death in a patient who died within 24 hour after taking the first dose of fingolimod was not conclusive; however a link to fingolimod or a drug interaction with fingolimod could not be ruled out.(2) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
There are 3 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Non-Live or Non-Replicating Vaccines/Fingolimod SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Fingolimod is an immunosuppressant and may alter the immune system's response to vaccines.(1) CLINICAL EFFECTS: Administration of a vaccine during and for 2 months following fingolimod therapy may result in decreased effectiveness of the vaccine.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ideally, administer vaccines prior to initiating fingolimod therapy. The immune response to non-live vaccines should be monitored in patients receiving fingolimod or who have received fingolimod in the previous two months. Vaccinations given during and for 2 months after stopping fingolimod therapy may need to be repeated.(1,2) The Centers for Disease Control's (CDC) Advisory Committee on Immunization Practices (ACIP) states that non-live vaccines should be used with caution in patients who are severely immunosuppressed. Patients who are vaccinated within the 14 days prior to initiating immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after immunosuppressive therapy is discontinued when immune competence is restored.(3) DISCUSSION: Vaccinations may be less effective during and for 2 months following fingolimod therapy(1) however they are considered safe to administer.(2) |
ACTHIB, ADACEL TDAP, AREXVY, AREXVY ANTIGEN COMPONENT, BEXSERO, BIOTHRAX, BOOSTRIX TDAP, CAPVAXIVE, COMIRNATY 2024-2025, CYFENDUS (NATIONAL STOCKPILE), DAPTACEL DTAP, ENGERIX-B ADULT, ENGERIX-B PEDIATRIC-ADOLESCENT, GARDASIL 9, HAVRIX, HEPLISAV-B, HIBERIX, IMOVAX RABIES VACCINE, INFANRIX DTAP, IPOL, IXIARO, JYNNEOS, JYNNEOS (NATIONAL STOCKPILE), KINRIX, MENQUADFI, MENVEO A-C-Y-W-135-DIP, MENVEO MENA COMPONENT, MENVEO MENCYW-135 COMPONENT, MODERNA COVID 24-25(6M-11Y)EUA, MRESVIA, NOVAVAX COVID 2024-2025 (EUA), PEDIARIX, PEDVAXHIB, PENBRAYA, PENBRAYA MENACWY COMPONENT, PENBRAYA MENB COMPONENT, PENMENVY MEN A-B-C-W-Y, PENMENVY MENACWY COMPONENT, PENMENVY MENB COMPONENT, PENTACEL, PENTACEL ACTHIB COMPONENT, PENTACEL DTAP-IPV COMPONENT, PFIZER COVID 2024-25(5-11Y)EUA, PFIZER COVID 2024-25(6M-4Y)EUA, PNEUMOVAX 23, PREVNAR 20, QUADRACEL DTAP-IPV, RABAVERT, RECOMBIVAX HB, SHINGRIX, SHINGRIX GE ANTIGEN COMPONENT, SPIKEVAX 2024-2025, TENIVAC, TICOVAC, TRUMENBA, TWINRIX, TYPHIM VI, VAQTA, VAXELIS, VAXNEUVANCE, VIMKUNYA |
| Fingolimod/Ketoconazole SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Systemic ketoconazole may inhibit the metabolism of fingolimod via CYP4F2. CLINICAL EFFECTS: Coadministered fingolimod and ketoconazole increases blood levels of fingolimod and its active metabolite fingolimod-phosphate 1.7-fold, increasing the risk for adverse reactions. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of fingolimod recommends close monitoring in patients on concomitant therapy due to the greater risk for adverse effects.(1,2) DISCUSSION: The primary metabolic pathway of fingolimod is CYP4F2 with minor contributions by CYP3A4, CYP2E1 and other CYP P-450 enzymes. As ketoconazole is a potent inhibitor or CYP4F2 and CYP3A4, a drug interaction study was performed. In a 2-period crossover study, healthy subjects received ketoconazole 200mg twice daily for 9 days, followed by a single dose of fingolimod 5 mg (i.e. 10 times recommended dose). The area-under-curve (AUC) for both fingolimod and the active metabolite fingolimod-phosphate, increased 1.7 fold.(1,2) |
KETOCONAZOLE |
| Fingolimod/QT Prolonging Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator. Initiation of fingolimod has a negative chronotropic effect leading to a mean decrease in heart rate of 13 beats per minute (bpm) after the first dose. The first dose has also been associated with heart block.(1-3) Fingolimod 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 the reduction of lymphocyte migration into the central nervous system.(1-3) CLINICAL EFFECTS: The heart rate lowering effect of fingolimod is biphasic with an initial decrease usually within 6 hours, followed by a second decrease 12 to 24 hours after the first dose. Symptomatic bradycardia and heart block, including third degree block, have been observed. Bradycardia may be associated with an increase in the QTc interval, increasing the risk for torsades de pointes. There is no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment.(1-3) PREDISPOSING FACTORS: Pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, a prolonged QTc interval prior to fingolimod initiation, factors associated with QTc prolongation (e.g. hypokalemia, hypomagnesemia), or concomitant treatment with QT prolonging agents may increase risk for cardiovascular toxicity due to fingolimod. The risk of QT prolongation or torsades de pointes may also be increased in patients with a history of torsades de pointes, hypocalcemia, bradycardia, female gender, or advanced age.(4) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of the QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(4) PATIENT MANAGEMENT: Patients with a baseline QTc interval greater than or equal to 500 milliseconds should not be started on fingolimod. Patients with pre-existing cardiovascular or cerebrovascular disease (e.g. heart failure, ischemic heart disease, history of myocardial infarction, stroke, or heart block), severe untreated sleep apnea, or a prolonged QTc interval prior to fingolimod initiation should receive cardiologist consultation to evaluate the risks of fingolimod therapy. In all patients, first dose monitoring is recommended to monitor for bradycardia for the first 6 hours. Check blood pressure and pulse hourly. ECG monitoring is recommended prior to dosing and at the end of the observation period. US monitoring recommendations include additional monitoring for the following patients:(1) If heart rate (HR) is less than 45 beats per minute (bpm), the heart rate 6 hours postdose is at the lowest value postdose, or if the ECG shows new onset of second degree or higher AV block at the end of the monitoring period, then monitoring should continue until the finding has resolved. Continuous overnight ECG monitoring is recommended in patients requiring pharmacologic intervention for symptomatic bradycardia, some preexisting heart and cerebrovascular conditions, prolonged QTc before dosing or during 6 hours observation, concurrent therapy with QT prolonging drugs, or concurrent therapy with drugs that slow heart rate or AV conduction. Consult the prescribing information for full monitoring recommendations. United Kingdom recommendations:(3) Obtain a 12-lead ECG prior to initiating fingolimod therapy. Consult a cardiologist for pretreatment risk-benefit assessment if patient has a resting heart rate less than 55 bpm, history of syncope, second degree or greater AV block, sick-sinus syndrome, concurrent therapy with beta-blockers, Class Ia, or Class III antiarrhythmics, heart failure or other significant cardiovascular disease. Perform continuous ECG monitoring, measure blood pressure and heart rate every hour, and perform a 12-lead ECG 6 hours after the first dose. Monitoring should be extended beyond 6 hours if symptomatic bradycardia or new onset of second degree AV block, Mobitz Type II or third degree AV block has occurred at any time during the monitoring period. If heart rate 6 hours after the first dose is less than 40 bpm, has decreased more than 20 bpm compared with baseline, or if a new onset second degree AV block, Mobitz Type I (Wenckebach) persists, then monitoring should also be continued. If fingolimod treatment is discontinued for more than two weeks, the effects on heart rate and conduction could recur. Thus, first dose monitoring precautions should be followed upon reintroduction of fingolimod. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: After the first dose of fingolimod, heart rate decrease may begin within an hour. Decline is usually maximal at approximately 6 hours followed by a second decrease 12 to 24 hours after the first dose. The second dose may further decrease heart rate, but the magnitude of change is smaller than the first dose. With continued, chronic dosing, heart rate gradually returns to baseline in about one month.(1,2) In a thorough QT interval study of doses of 1.25 or 2.5 mg fingolimod at steady-state, when a negative chronotropic effect of fingolimod was still present, fingolimod treatment resulted in a prolongation of QTc, with the upper boundary of the 90% confidence interval (CI) of 14.0 msec. The cause of death in a patient who died within 24 hour after taking the first dose of fingolimod was not conclusive; however a link to fingolimod or a drug interaction with fingolimod could not be ruled out.(1) |
ADLARITY, AGRYLIN, ALFUZOSIN HCL ER, ANAGRELIDE HCL, APOKYN, APOMORPHINE HCL, ARICEPT, ASPRUZYO SPRINKLE, ATOMOXETINE HCL, AVELOX IV, AZITHROMYCIN, BARHEMSYS, CAPRELSA, CELEXA, CESIUM CHLORIDE, CHLOROQUINE PHOSPHATE, CHLORPROMAZINE HCL, CILOSTAZOL, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W, CITALOPRAM HBR, CLARITHROMYCIN, CLARITHROMYCIN ER, COARTEM, DIFLUCAN, DIPRIVAN, DISKETS, DONEPEZIL HCL, DONEPEZIL HCL ODT, DROPERIDOL, E.E.S. 200, E.E.S. 400, EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, EGATEN, ERIBULIN MESYLATE, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, ERZOFRI, ESCITALOPRAM OXALATE, FANAPT, FARESTON, FLUCONAZOLE, FLUCONAZOLE-NACL, GALANTAMINE ER, GALANTAMINE HBR, GALANTAMINE HYDROBROMIDE, GATIFLOXACIN SESQUIHYDRATE, GEODON, GRANISETRON HCL, HALAVEN, HALDOL DECANOATE 100, HALOPERIDOL, HALOPERIDOL DECANOATE, HALOPERIDOL DECANOATE 100, HALOPERIDOL LACTATE, HYDROXYCHLOROQUINE SULFATE, HYDROXYZINE HCL, HYDROXYZINE PAMOATE, IBTROZI, IGALMI, INVEGA, INVEGA HAFYERA, INVEGA SUSTENNA, INVEGA TRINZA, ISRADIPINE, ISTURISA, KALETRA, LANSOPRAZOL-AMOXICIL-CLARITHRO, LENVIMA, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, LEVOFLOXACIN-D5W, LEXAPRO, LOFEXIDINE HCL, LOPINAVIR-RITONAVIR, LUCEMYRA, MEMANTINE HCL-DONEPEZIL HCL ER, METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL, METHADONE INTENSOL, METHADOSE, MOXIFLOXACIN, MOXIFLOXACIN HCL, NAMZARIC, NEXAVAR, NOXAFIL, NUPLAZID, OFLOXACIN, OMECLAMOX-PAK, ONAPGO, ONDANSETRON HCL, ONDANSETRON HCL-0.9% NACL, PALIPERIDONE ER, PENTAM 300, PENTAMIDINE ISETHIONATE, PIMOZIDE, PLAQUENIL, POSACONAZOLE, PROPOFOL, QUETIAPINE FUMARATE, QUETIAPINE FUMARATE ER, RALDESY, RANOLAZINE ER, RETEVMO, ROZLYTREK, SANCUSO, SEROQUEL, SEROQUEL XR, SEVOFLURANE, SIGNIFOR, SIGNIFOR LAR, SIRTURO, SORAFENIB, SOVUNA, SUSTOL, SYMFI, TAGRISSO, THIORIDAZINE HCL, THIORIDAZINE HYDROCHLORIDE, TIBSOVO, TOLTERODINE TARTRATE, TOLTERODINE TARTRATE ER, TOREMIFENE CITRATE, TRAZODONE HCL, ULTANE, UROXATRAL, VFEND, VFEND IV, VIBATIV, VOQUEZNA TRIPLE PAK, VORICONAZOLE, WAKIX, XENLETA, XOLREMDI, XOSPATA, ZELBORAF, ZIPRASIDONE HCL, ZIPRASIDONE MESYLATE, ZITHROMAX, ZITHROMAX TRI-PAK, ZUNVEYL, ZYKADIA |
The following contraindication information is available for GILENYA (fingolimod hcl):
Drug contraindication overview.
*Recent (in the past 6 months) myocardial infarction (MI), unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or class III or IV heart failure. *History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome unless patient has a functioning pacemaker. *Baseline QTc interval >=500 msec.
*Cardiac arrhythmia requiring concomitant use of class Ia or class III antiarrhythmic agents. *History of hypersensitivity reaction to fingolimod or any ingredient in the formulation. *Concomitant use with other products containing fingolimod.
*Recent (in the past 6 months) myocardial infarction (MI), unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or class III or IV heart failure. *History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome unless patient has a functioning pacemaker. *Baseline QTc interval >=500 msec.
*Cardiac arrhythmia requiring concomitant use of class Ia or class III antiarrhythmic agents. *History of hypersensitivity reaction to fingolimod or any ingredient in the formulation. *Concomitant use with other products containing fingolimod.
There are 14 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| 30 day risk period post-myocardial infarction |
| Acute myocardial infarction |
| Acutely decompensated chronic heart failure |
| Cerebrovascular accident |
| Complete atrioventricular block |
| Congenital long QT syndrome |
| Lactation |
| Pregnancy |
| Progressive multifocal leukoencephalopathy |
| Prolonged QT interval |
| Second degree atrioventricular heart block |
| Severe chronic heart failure |
| Transient cerebral ischemia |
| Unstable angina pectoris |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Bradycardia |
| Hypertension |
| Hypokalemia |
| Hypomagnesemia |
| Macular retinal edema |
| Severe infection |
| Sick sinus syndrome |
| Sleep apnea |
There are 8 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Basal cell carcinoma of skin |
| Diabetes mellitus |
| Disease of liver |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Leukopenia |
| Pre-malignant skin lesion |
| Pulmonary disease |
| Uveitis |
The following adverse reaction information is available for GILENYA (fingolimod hcl):
Adverse reaction overview.
Adverse effects reported in >=10% of patients receiving fingolimod and more frequently than with placebo include headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity.
Adverse effects reported in >=10% of patients receiving fingolimod and more frequently than with placebo include headache, liver transaminase elevation, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in extremity.
There are 49 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abnormal hepatic function tests Diarrhea Dyspnea Increased alanine transaminase Increased aspartate transaminase |
Bradycardia Decrease in lung function measured by spirometer Fungal infection Hyperbilirubinemia Hypertension Hypertriglyceridemia Hypotension Infection Leukopenia Migraine Pneumonia |
| Rare/Very Rare |
|---|
|
Acute hepatic failure Angioedema Atrioventricular block Basal cell carcinoma of skin Cerebrovascular accident Chest pain Cholestatic hepatitis Cryptococcosis Cutaneous t-cell lymphoma Hemolytic anemia Hepatocellular damage Herpes simplex encephalitis Herpes simplex infection Herpes zoster Herpes zoster meningitis Human papillomavirus infection Kaposi's sarcoma Macular retinal edema Malignant lymphoma Malignant melanoma Merkel cell carcinoma Mycosis fungoides Opportunistic fungal infection Opportunistic viral infection Palpitations Posterior reversible encephalopathy syndrome Progressive multifocal leukoencephalopathy Prolonged PR interval Prolonged QT interval Seizure disorder Squamous cell carcinoma of skin Syncope Thrombocytopenic disorder |
There are 29 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Back pain Bronchitis Cough Depression Headache disorder Hypercholesterolemia Influenza Nausea Pain in extremities Sinusitis |
Actinic keratosis Alopecia Blurred vision Cutaneous papilloma Dizziness Eczema Gastroenteritis General weakness Lymphopenia Pruritus of skin Tinea versicolor Weight loss |
| Rare/Very Rare |
|---|
|
Arthralgia Fatigue Myalgia Skin rash Urticaria Vomiting |
The following precautions are available for GILENYA (fingolimod hcl):
Safety and efficacy of fingolimod in pediatric patients younger than 10 years of age have not been established. In the clinical study establishing efficacy of fingolimod in pediatric patients 10 years of age or older, adverse effects were generally similar to those observed in adults, with the exception of seizures, which occurred at a higher rate (5.6%) in fingolimod-treated pediatric patients. In juvenile animal toxicity studies, changes in bone mineral density, neurobehavioral abnormalities, delayed sexual maturation, and decreased T-cell dependent antibody response were observed when fingolimod was administered orally to young rats. It is recommended that pediatric patients receive all age-appropriate vaccinations according to current immunization guidelines, if possible, prior to initiation of fingolimod therapy.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
There are no adequate data regarding the developmental risk associated with the use of fingolimod during pregnancy; however, teratogenic and embryolethal effects have been demonstrated in animal studies with doses similar to or less than those used clinically. Women of childbearing potential should use effective contraception during and for 2 months following fingolimod therapy. Consider the possibility of severe increase in disability in women who discontinue fingolimod for pregnancy.
Many cases in which an increase in disability occurred after stopping fingolimod were reported in patients who had discontinued the drug because of pregnancy or planned pregnancy. In females planning to become pregnant, fingolimod should be stopped 2 months before planned conception. A pregnancy registry has been established to monitor the pregnancy outcomes of women exposed to fingolimod during pregnancy.
Clinicians are encouraged to enroll patients in the registry by calling 877-598-7237, emailing gpr@quintiles.com, or visiting https://www.gilenyapregnancyregistry.com
Many cases in which an increase in disability occurred after stopping fingolimod were reported in patients who had discontinued the drug because of pregnancy or planned pregnancy. In females planning to become pregnant, fingolimod should be stopped 2 months before planned conception. A pregnancy registry has been established to monitor the pregnancy outcomes of women exposed to fingolimod during pregnancy.
Clinicians are encouraged to enroll patients in the registry by calling 877-598-7237, emailing gpr@quintiles.com, or visiting https://www.gilenyapregnancyregistry.com
Fingolimod is distributed into milk in rats. It is not known whether the drug is distributed into human milk. Generally, when a drug is present in animal milk, it is likely present in human milk.
The effects of the drug on the nursing infant or on milk production also are not known. Consider the benefits of breastfeeding along with the woman's clinical need for fingolimod and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition.
The effects of the drug on the nursing infant or on milk production also are not known. Consider the benefits of breastfeeding along with the woman's clinical need for fingolimod and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition.
Experience in geriatric patients >=65 years of age is insufficient to determine whether they respond differently than younger adults. Use fingolimod with caution in geriatric patients, reflecting the greater frequency of decreased hepatic and renal function and of concomitant disease and other drug therapy.
The following prioritized warning is available for GILENYA (fingolimod hcl):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for GILENYA (fingolimod hcl)'s list of indications:
| Relapsing form of multiple sclerosis | |
| G35 | Multiple sclerosis |
| Secondary progressive multiple sclerosis | |
| G35 | Multiple sclerosis |
Formulary Reference Tool