Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 0.25mg
  • 0.5mg
more...

Multiple Sclerosis

Indicated for relapsing forms of multiple sclerosis (MS)

0.5 mg PO qDay

Doses >0.5 mg are associated with a greater incidence of adverse reactions without additional benefit

See also Administration

Dosage Modifications

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: Monitor therapy; exposure the drug may double in severe hepatic impairment

Renal impairment

  • Mild-to-moderate: Not assessed
  • Severe: Blood level of some fingolimod metabolites is increased (up to 13-fold); toxicity of these metabolites has not been fully explored

Dosing Considerations

Assessment prior to initiating treatment

  • Obtain a cardiac evaluation in patients with certain preexisting conditions; determine whether patients are taking drugs that could slow heart rate or atrioventricular conduction
  • Review recent CBC results
  • If patients are taking antineoplastic, immunosuppressive, or immune-modulating therapies, or has a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment
  • Test for antibodies to varicella zoster virus (VZV); VZV vaccination should be recommend prior to commencing treatment to antibody negative patients

Reinitiation of therapy following discontinuation

  • If discontinued for >14 days, after the first month of treatment, the same first dose monitoring should be applied upon reinitiation
  • Within the first 2 weeks of treatment, first dose procedures are recommended after an interruption of 1 day or more
  • During weeks 3 and 4 of treatment, first dose procedures are recommended after an interruption >7 days

Demyelinating Polyneuropathy (Orphan)

Treatment of chronic inflammatory demyelinating polyneuropathy

Orphan indication sponsor

  • Novartis Pharmaceutical Corporation; One Health Plaza; East Hanover, NJ 07936

Dosage Forms & Strengths

capsule

  • 0.25mg
  • 0.5mg
more...

Multiple Sclerosis

Indicated for relapsing forms of MS in patients ≥10 years

<10 years: Safety and efficacy not established

≥10 years weighing ≤40 kg: 0.25 mg PO qDay

≥10 years weighing >40 kg: 0.5 mg PO qDay

Doses >0.5 mg are associated with a greater incidence of adverse reactions without additional benefit

See also Administration

Dosage Modifications

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: Monitor therapy; exposure the drug may double in severe hepatic impairment

Renal impairment

  • Mild-to-moderate: Not assessed
  • Severe: Blood level of some fingolimod metabolites is increased (up to 13-fold); toxicity of these metabolites has not been fully explored

Dosing Considerations

Assessment prior to initiating treatment

  • Obtain a cardiac evaluation in patients with certain preexisting conditions; determine whether patients are taking drugs that could slow heart rate or atrioventricular conduction
  • Review recent CBC results
  • If patients are taking antineoplastic, immunosuppressive, or immune-modulating therapies, or has a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment
  • Test for antibodies to varicella zoster virus (VZV); VZV vaccination should be recommend prior to commencing treatment to antibody negative patients; if possible, complete all immunizations in accordance with current immunization guidelines prior to initiating therapy

Reinitiation of therapy following discontinuation

  • If discontinued for >14 days, after the first month of treatment, the same first dose monitoring should be applied upon reinitiation
  • Within the first 2 weeks of treatment, first dose procedures are recommended after an interruption of 1 day or more
  • During weeks 3 and 4 of treatment, first dose procedures are recommended after an interruption >7 days
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Interactions

Interaction Checker

and fingolimod

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Headache (25%)

            Liver transaminase elevations (ALT/GGT/AST) (15%)

            Nausea (13%)

            Influenza viral infection (11%)

            Sinusitis (11%)

            Abdominal pain (11%)

            Diarrhea (12%)

            Cough (12%)

            1-10%

            Back pain (10%)

            Pain in extremity (10%)

            Herpes viral infections (9%)

            Dyspnea (9%)

            Depression (8%)

            Hypertension (8%)

            Bronchitis (8%)

            Sinusitis (7%)

            Dizziness (7%)

            Lymphopenia (7%)

            Hypertension (6%)

            Migraine (6%)

            Gastroenteritis (5%)

            Weight decreased (5%)

            Paresthesia (5%)

            Tinea infections (4%)

            Bradycardia (4%)

            Blurred vision (4%)

            Eye pain (3%)

            Alopecia (3%)

            Increased blood triglycerides (3%)

            Skin papilloma (3%)

            Bradycardia (3%)

            Herpes zoster (2%)

            Tinea versicolor (2%)

            Asthenia (2%)

            Actinic keratosis (2%)

            Leukopenia (2%)

            Basal cell carcinoma (2%)

            <1%

            Seizures (0.9%)

            Macular edema (0.4%)

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            Warnings

            Contraindications

            Hypersensitivity; observed reactions include rash, urticaria, and angioedema upon treatment initiation

            History within past 6 months of MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization or Class III/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 ms

            Coadministration with Class Ia or Class III antiarrhythmic drugs

            Cautions

            Bradyarrhythmia and atrioventricular blocks

            • Also see contraindications, dosing considerations, and drug interaction overview
            • Heart rate reduction
              • After the first dose, heart rate (HR) decrease starts within an hour; on Day 1, the maximum HR decline generally occurs within 6 hr and recovers, although not to baseline levels, by 8-10 hours postdose
              • Because of physiological diurnal variation, there is a second period of HR decrease within 24 hr after the first dose; in some patients, HR decrease during the second period is more pronounced than the decrease observed in the first 6 hr
              • Patients with some preexisting conditions (eg, ischemic heart disease, history of MI, CHF, 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
              • Before initiating treatment, evaluate patients at risk by a physician appropriately trained to conduct such evaluation, and, if treated with fingolimod, monitor patient overnight with continuous ECG in a medical facility after the first dose
            • Atrioventricular blocks
              • Transient AV conduction delays observed after initiating fingolimod
              • Conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hr on treatment, but they occasionally required treatment with atropine or isoproterenol

            Infections

            • Causes dose-dependent reduction in peripheral lymphocyte count to 20-30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues
            • May therefore increase risk of life-threatening and fatal infections (eg, disseminated varicella zoster, herpes simplex, or cryptococcal infections), including fatal meningitis, encephalitis, and multiorgan failure
            • Do not initiate with active acute or chronic infections until resolved; prior to initiation, a recent CBC (ie, within 6 months or after discontinuation of prior therapy) should be available
            • Patients without confirmed history of chickenpox or without documentation of full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating therapy; vaccination of antibody-negative patients is recommended prior to commencing therapy; postpone therapy 1 month to allow full effect of vaccination to occur
            • Postmarketing reports of serious infections include opportunistic pathogens including viruses John Cunningham virus (JCV), herpes simplex viruses 1 and 2, varicella-zoster virus), fungi (eg, cryptococci), and bacteria (eg, atypical mycobacteria) reported; patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and treatment
            • Cases of Kaposi’s sarcoma reported; patients with symptoms or signs consistent with Kaposi’s sarcoma should receive prompt diagnostic evaluation and management

            Progressive multifocal leukoencephalopathy

            • Progressive multifocal leukoencephalopathy (PML) reported; symptoms are diverse and included sudden onset of severe headache, altered mental status, progressive unilateral weakness, clumsiness, visual disturbances, and seizure; symptoms usually reversible but may evolve into ischemic stroke or cerebral hemorrhage and delay in diagnosis and treatment may lead to permanent neurological sequelae
            • An MRI scan may find brain lesions before symptoms develop Majority of cases occurred after 2 years of treatment

            Macular edema

            • Increases risk of macular edema (with or without visual symptoms)
            • Perform an examination of the fundus including the macula in all patients before initiating treatment and 3-4 months after starting treatment or any time after a patient reports visual disturbances while in therapy
            • History of diabetes mellitus or uveitis have increased risk of macular edema

            Posterior reversible encephalopathy syndrome

            • Rare cases of posterior reversible encephalopathy syndrome (PRES) reported in adults
            • Symptoms reported included sudden onset of severe headache, altered mental status, visual disturbances, and seizure
            • Symptoms are usually reversible, but may evolve into ischemic stroke or cerebral hemorrhage
            • Transient AV conduction delays observed after initiating fingolimod
            • Conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hr on treatment, but they occasionally required treatment with atropine or isoproterenol

            Respiratory effects

            • Dose-dependent reduction in FEV 1 and diffusion lung capacity for carbon monoxide (DLCO) observed as early as 1 month after fingolimod initiation
            • Spirometric evaluation of respiratory function and evaluation of DLCO should be performed during therapy if clinically indicated

            Liver injury

            • Liver injury with hepatocellular and/or cholestatic hepatitis reported
            • Recent (ie, within last 6 months) transaminase and bilirubin levels should be available before initiation
            • Monitor liver enzymes and bilirubin if symptoms develop suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine)
            • Discontinue if significant liver injury is confirmed

            Fetal risk

            • Based on animal studies, may cause fetal harm
            • It takes ~2 months to eliminate fingolimod from the body; therefore, women of childbearing potential should use effective contraception to avoid pregnancy during and for 2 months after stopping treatment (see Pregnancy)

            Increased blood pressure

            • In controlled clinical trials, adults treated with fingolimod 0.5 mg had an average increase of ~3 mmHg in systolic pressure and ~2 mmHg in diastolic pressure detected after ~1 month after initiation, and persisting with continued treatment
            • Monitor blood pressure during treatment

            Cutaneous malignancies

            • Increases risk of basal cell carcinoma (BCC) and melanoma
            • Melanoma and merkel cell carcinoma reported postmarketing
            • Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer
            • Advise patients to promptly evaluate suspicious skin lesions and protect themselves from sunlight and UV light exposure

            Immune system effects

            • Fingolimod remains in the blood and has pharmacodynamic effects, including decreased lymphocyte counts, for up to 2 months following the last dose
            • Lymphocyte counts generally return normalizes within 1-2 months after discontinuing drug
            • Because of the continuing pharmacodynamic effects, initiating other drugs during this period warrants the same considerations needed for concomitant administration (eg, additive immunosuppressant effects) (see Drug Interaction Overview)

            Hypersensitivity reactions

            • Hypersensitivity reactions, including rash, urticaria, and angioedema have been reported
            • Contraindicated in patients with history of hypersensitivity to fingolimod or any of its excipients (see Contraindications)

            Drug interactions overview

            • Inhibitors or inducers of CYP4F2 and possibly other CYP4F isozymes might alter the exposure of fingolimod
            • Coadministration with ketoconazole (a potent inhibitor of CYP3A and CYP4F) increased fingolimod blood levels by 1.7-fold; monitor closely if coadministered
            • Antineoplastic, immunosuppressive, or immunomodulating therapies
              • Risk for additive systemic immunosuppression if coadministered with antineoplastics, immunosuppressives, or immunomodulators
              • Avoid unintended additive immunosuppression when switching from drugs with prolonged immune effects (eg, natalizumab, teriflunomide, mitoxantrone)
            • Vaccines
              • Fingolimod reduces immune response to vaccination; vaccination may be less effective during and for up to 2 months after discontinuing fingolimod
              • Avoid use of live attenuated vaccines during and for 2 months after treatment with because of the risk of infection
              • If possible, pediatric patients should be brought up to date with all immunizations in agreement with current immunization guidelines before initiating fingolimod
            • QT prolonging drugs
              • Not studied in patients treated with drugs that prolong the QT interval, which have been associated with cases of torsades de pointes in patients with bradycardia
              • Since treatment initiation of fingolimod results in decreased heart rate and may prolong the QT interval, patients on QT prolonging drugs with a known risk of torsades de pointes should be monitored overnight with continuous ECG in a medical facility
            • Drugs that slow HR or AV conduction
              • Experience with concurrent therapy with drugs that slow the heart rate or atrioventricular conduction (eg, beta blockers, digoxin, or heart rate-slowing calcium channel blockers [diltiazem, verapamil]) is limited
              • Fingolimod may result in decreased heart rate; therefore, coadministration with the aforementioned drugs during fingolimod initiation may be associated with severe bradycardia or heart block
              • Seek advice from the physician prescribing these drugs regarding the possibility to switch to drugs that do not slow HR or AV conduction before initiating fingolimod
              • Patients who cannot switch should have overnight continuous ECG monitoring after the first fingolimod dose
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            Pregnancy & Lactation

            Pregnancy

            There are no adequate data on the developmental risk associated with drug use in pregnant women

            Pregnancy exposure registry monitors pregnancy outcomes in women exposed to fingolimod during pregnancy; physicians and patients are encouraged to enroll in the pregnancy registry by calling 1-877-598-7237, sending an email to gpr@quintiles.com, or visiting www.gilenyapregnancyregistry.com

            Animal data

            • In oral studies conducted in rats and rabbits, fingolimod demonstrated developmental toxicity, including an increase in malformations (rats) and embryo lethality, when given to pregnant animals
            • In rats, highest no-effect dose was less than the recommended human dose of 0.5 mg/day on a body surface area (mg/m²) basis; most common fetal visceral malformations in rats were persistent truncus arteriosus and ventricular septal defect; receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis

            Contraception

            • Before treatment initiation, counsel women of childbearing potential regarding potential for serious fetal risk and the need for effective contraception during treatment
            • Since it takes ~2 months to eliminate the compound from the body after discontinuing treatment, potential risk to the fetus may persist and women should use effective contraception during this period

            Lactation

            There are no data on the presence of fingolimod in human milk, the effects on the breastfed infant, or the effects of the drug on milk production

            Fingolimod is excreted in the milk of treated rats

            Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for fingolimod and any potential adverse effects on the breastfed infant from fingolimod or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
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            Pharmacology

            Mechanism of Action

            Sphingosine 1-phosphate receptor modulator; metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate.  

            Binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5; blocks lymphocyte capacity to egress from lymph nodes, and thereby reduces the lymphocyte count in peripheral blood

            The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system

            Absorption

            Bioavailability: 93%

            Plasma Time: 12-16 hr

            Steady-State: Time to steady state is 1-2 months following daily dosing; steady-state levels approximately 10-fold greater than initial dose

            Distribution

            86% distributed in RBCs

            Protein Bound: >99%

            Vd: 1200 L

            Metabolism

            Primarily by CYP4F2, minor substrate of CYP2D6, 2E1, 3A4, and 4F12

            Elimination

            Half-life: 6-9 days

            Clearance: 6.3 L/hr

            Excretion: Feces (<2.5%), urine (81% as inactive metabolites)

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            Administration

            Oral Administration

            May take with or without food

            Also see Dosing Considerations

            First dose monitoring

            • Administer in a setting which has the ability to manage symptomatic bradycardia; observe heart rate (HR) and blood pressure hourly for at least 6 hr post dose; obtain ECG prior to first dose and at the end of observation period
            • Additional monitoring after 6 hr
              • Heart rate 6 hours postdose is <45 bpm
              • Heart rate 6 hours postdose at the lowest post-dose value (suggesting maximal effect on heart rate may not yet have occurred), or if new onset second-degree or higher AV block occurs
            • Overnight monitoring
              • Institute continuous overnight ECG monitoring in a medical facility:
              • Patients that require pharmacologic intervention for symptomatic bradycardia; these patients, first dose monitoring strategy should be repeated after second dose of fingolimod
              • Patients with some preexisting heart and cerebrovascular conditions
              • Patients with a prolonged QTc interval before dosing or during 6 hr observation, or at additional risk for QT prolongation, or on concurrent therapy with QT prolonging drugs
              • Patients receiving concurrent therapy with drugs that slow heart rate or atrioventricular conduction

            Storage

            Capsules: Store at 25°C (77°F); excursions permitted to 15-30°C (59–86°F); protect from moisture

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.