Gilenya Fingolimod Hydrochloride Capsules

1. Indications and Usage
Relapsing Multiple Sclerosis:
Indicated for the treatment of patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults and pediatric patients 10 years of age and older.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Swallow capsules whole; do not open or crush. Can be taken with or without food.
Recommended Dosage:
Adults and Pediatric Patients (>40 kg): 0.5 mg once daily.
Pediatric Patients (10 to <40 kg body weight): 0.25 mg once daily.
Note: Doses higher than 0.5 mg provide no additional benefit and are associated with an increased rate of adverse reactions.
First-Dose Monitoring:
Because fingolimod initiation results in a decrease in heart rate, all patients must undergo first-dose monitoring in a healthcare facility equipped to treat symptomatic bradycardia. This includes obtaining an ECG before dosing and monitoring hourly pulse and blood pressure for 6 hours post-dose. Extended overnight monitoring may be required if heart rate drops significantly or conduction abnormalities occur.
Missed Doses / Treatment Interruption:
If a dose is missed during the first two weeks of treatment, medical supervision and first-dose monitoring are required for the next dose. If treatment is interrupted for more than 14 days after the first month of therapy, first-dose monitoring procedures must be repeated upon reinitiation.
3. Mechanism of Action
S1P Receptor Modulation:
Fingolimod is phosphorylated in vivo to form fingolimod-phosphate, which acts as a functional antagonist at sphingosine 1-phosphate (S1P) receptors 1, 3, 4, and 5.
Lymphocyte Sequestration:
By binding to S1P receptors on lymphocytes, fingolimod prevents their egress from lymph nodes. This sequestration reduces the number of circulating autoreactive lymphocytes capable of infiltrating the central nervous system (CNS), thereby reducing CNS inflammation and demyelination characteristic of multiple sclerosis.
4. Safety and Warnings
Cardiovascular Effects (Bradycardia & AV Block):
Initiation causes transient bradycardia and atrioventricular (AV) conduction delays. It is contraindicated in patients with recent myocardial infarction, unstable angina, stroke, NYHA Class III/IV heart failure, or high-degree AV block without a pacemaker.
Infections & Immunosuppression:
Increases the risk of infections, including opportunistic infections like Progressive Multifocal Leukoencephalopathy (PML). Test for varicella-zoster virus (VZV) antibodies prior to initiation; vaccinate VZV-negative patients one month before starting therapy. Avoid live-attenuated vaccines during treatment and for 2 months after discontinuation.
Macular Edema:
Risk of fingolimod-associated macular edema. Baseline ophthalmologic evaluation is recommended, with follow-up exams at 3–4 months and periodically thereafter. Risk is higher in patients with diabetes or a history of uveitis.
Hepatotoxicity:
Elevations in liver enzymes can occur. Assess liver function tests within 6 months prior to initiation and monitor periodically. Discontinue if significant hepatic injury is suspected.
Post-Treatment Disease Rebound:
Severe worsening of MS, including tumor-like lesions, has been reported within 12 weeks (up to 24 weeks) after stopping fingolimod. Close clinical and MRI monitoring is required upon discontinuation.
Embryo-Fetal Toxicity:
May cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for 2 months after stopping.
5. Adverse Reactions
Most Common (Incidence ≥10%):
Headache, elevated liver enzymes (ALT), diarrhea, cough, influenza, sinusitis, back pain, and abdominal pain.
Other Significant Reactions:
Lymphopenia, decreased pulmonary function (FEV1 and DLCO reductions), hypertension, and peripheral skin cancers (basal cell carcinoma, melanoma).
6. Drug Interactions
Heart Rate-Lowering Drugs:
Concomitant use with beta-blockers, non-dihydropyridine calcium channel blockers (e.g., verapamil, diltiazem), or antiarrhythmics (Class Ia or III) may cause severe bradycardia or heart block. Avoid concomitant use or conduct intensive cardiac monitoring.
Strong CYP Inhibitors:
Co-administration with strong CYP inhibitors (e.g., ketoconazole) increases fingolimod exposure. Monitor these patients closely.
Immunosuppressants/Antineoplastics:
Concurrent or recent use of immunosuppressive or antineoplastic therapies may lead to unintended additive immunosuppression. Exercise caution when transitioning between therapies.
Vaccines:
Vaccinations may be less effective during treatment and for up to 2 months post-treatment. Live vaccines should be avoided due to infection risk.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Fingolimod Hydrochloride.
Available Strength: 0.5 mg hard gelatin capsules.
Appearance: White to off-white powder inside a hard capsule.
Pharmacokinetics:
Peak plasma concentrations are reached within 12–16 hours. The half-life is approximately 6 to 9 days. It is extensively metabolized (primarily via CYP4F2) and excreted mainly in urine as inactive metabolites.
Storage:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F). Keep in original package to protect from moisture.