FINGOLIMOD HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FINGOLIMOD HYDROCHLORIDE (FINGOLIMOD HYDROCHLORIDE).
Sphingosine 1-phosphate receptor modulator; binds to S1P receptors (S1P1, S1P3, S1P4, S1P5) on lymphocytes, causing receptor internalization and preventing egress from lymph nodes, thereby reducing circulating lymphocyte counts.
| Metabolism | Primarily metabolized by cytochrome P450 4F2 (CYP4F2) via omega-hydroxylation; also undergoes hydrolysis by non-CYP enzymes. Minor contribution from CYP3A4. |
| Excretion | Primarily hepatic metabolism (CYP4F2) with subsequent biliary/fecal elimination (81% of total clearance); renal excretion accounts for <2.5% of unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 6–9 days; due to extensive tissue distribution, steady-state is reached within 1–2 months of daily dosing. |
| Protein binding | >99.7% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Approximately 1700 L (17 ± 6 L/kg) indicating extensive distribution into tissues, including erythrocytes, brain, and adipose tissue. |
| Bioavailability | Oral bioavailability is approximately 93% (range 80–100%). |
| Onset of Action | Oral: Reduction in lymphocyte count occurs within 4–6 hours after the first dose; maximal effect on heart rate (first-dose bradycardia) is observed at 4–5 hours post-dose. |
| Duration of Action | Duration of pharmacological effect (lymphocyte sequestration) persists for up to 6 weeks after discontinuation; complete recovery of lymphocyte count may take 1–2 months. |
0.5 mg orally once daily
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min. Fingolimod has not been studied in ESRD (GFR <15 mL/min) or dialysis; use caution. |
| Liver impairment | Child-Pugh A or B: No dose adjustment. Child-Pugh C: Contraindicated. |
| Pediatric use | For patients ≥10 years and >40 kg: 0.5 mg orally once daily. For patients <40 kg or <10 years: Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use caution due to increased risk of bradycardia, infections, and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FINGOLIMOD HYDROCHLORIDE (FINGOLIMOD HYDROCHLORIDE).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not established. Due to potential for serious adverse reactions in breastfed infants (e.g., immunosuppression), advise against breastfeeding during therapy and for 2 months after last dose. |
| Teratogenic Risk | First trimester: FDA Pregnancy Category C. Animal studies show embryolethality, fetal malformations (including persistent truncus arteriosus and ventricular septal defects) and increased resorptions. In humans, S1P receptor modulators are associated with a 2-fold increase in major congenital malformations when exposed in the first trimester. Second and third trimesters: Risk of fetal bradycardia, QT prolongation, and growth restriction due to maternal lymphopenia and immune modulation. |
■ FDA Black Box Warning
Increased risk of serious infections, including life-threatening opportunistic infections such as progressive multifocal leukoencephalopathy (PML), cryptococcal meningitis, and herpes virus infections. Baseline and periodic monitoring required.
| Serious Effects |
Hypersensitivity to fingolimod or any component. Recent (within 6 months) myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure, or NYHA class III/IV heart failure. History of Mobitz type II 2nd-degree or 3rd-degree AV block or sick sinus syndrome unless pacemaker in place. Severe untreated sleep apnea. Baseline prolonged QTc interval (>500 msec) or concurrent Class Ia or Class III antiarrhythmic drugs.
| Precautions | Risk of bradyarrhythmia and atrioventricular block at treatment initiation; require ECG monitoring. Macular edema, especially in patients with uveitis or diabetes. Reduced pulmonary function; avoid in severe respiratory disease. Posterior reversible encephalopathy syndrome (PRES). Hepatic injury; monitor liver enzymes. Fetal harm; effective contraception required. Increased risk of infections; withhold during serious infection. Avoid live vaccines during and for 2 months after treatment. |
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| Fetal Monitoring | Baseline and periodic complete blood count (lymphocyte count), liver function tests, ophthalmologic exam (for macular edema), ECG (baseline and after first dose for bradycardia), blood pressure monitoring, and fetal ultrasound for growth and anatomy in the second trimester if exposed. |
| Fertility Effects | No direct human fertility studies. Animal studies show no impairment of fertility at doses up to 1 mg/kg/day. However, due to its immunosuppressive effects, counseling on family planning is recommended. |
| Food/Dietary |
| Grapefruit and grapefruit juice increase fingolimod exposure by inhibiting CYP3A4 and CYP4F2; avoid concurrent consumption. |
| Clinical Pearls | First-dose monitoring required for 6 hours post-initial dose due to bradycardia risk; obtain baseline ECG, blood pressure, and heart rate. Avoid use in patients with recent MI, unstable angina, stroke, TIA, or certain arrhythmias. Vaccinate against varicella zoster virus (VZV) before initiation if no history of chickenpox or vaccination. Monitor for macular edema, especially in patients with diabetes or uveitis. Lymphopenia is expected; do not discontinue for low lymphocyte counts unless infection occurs. |
| Patient Advice | Take exactly as prescribed; do not stop without consulting your doctor. · You will be observed for at least 6 hours after your first dose to monitor heart rate. · Report any signs of infection (fever, cough, painful urination) immediately. · Report any vision changes, such as blurriness or blind spots. · Avoid live vaccines while taking this medication and for 2 months after stopping. · Fingolimod can harm a fetus; use effective contraception during treatment and for 2 months after stopping. · Avoid grapefruit and grapefruit juice as they may increase side effects. |