FINGOLIMOD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FINGOLIMOD (FINGOLIMOD).
Sphingosine 1-phosphate receptor modulator; acts as a functional antagonist by downregulating S1P receptors on lymphocytes, preventing their egress from lymph nodes and reducing peripheral lymphocyte count.
| Metabolism | Primarily metabolized by CYP4F2 via ω-hydroxylation; minor contributions from CYP2D6, CYP2E1, CYP3A4, and CYP4F12. Also undergoes reversible phosphorylation to active metabolite fingolimod-phosphate. |
| Excretion | Primarily via biliary/fecal excretion (81% of dose recovered in feces as metabolites); renal excretion accounts for <2.5% of unchanged drug. |
| Half-life | Terminal elimination half-life is 6–9 days due to enteropathic recirculation and high Vd; clinical context: steady state reached in 1–2 months, duration of immunosuppression persists for weeks after discontinuation. |
| Protein binding | >99.7% bound to human serum albumin; minor binding to lipoproteins. |
| Volume of Distribution | Vd approximately 1000 L/kg (17,000 L); extensive distribution into tissues, particularly lung, blood cells, and CNS. |
| Bioavailability | Oral bioavailability is approximately 93% following a single 5 mg dose; food does not significantly affect absorption. |
| Onset of Action | Oral: reduction in lymphocyte count observed within 4–6 hours; maximal effect on lymphocyte recirculation occurs by 12–24 hours; clinical efficacy in MS may take weeks to months. |
| Duration of Action | Lymphocyte count returns to normal range within 6–8 weeks after last dose; immunosuppressive effects may persist for up to 2 months due to prolonged half-life. |
0.5 mg orally once daily
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not studied in severe renal impairment (GFR <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh Class A or B: No dose adjustment. Child-Pugh Class C: Contraindicated. |
| Pediatric use | For patients 10 years and older weighing >40 kg: 0.5 mg orally once daily. For patients <10 years or ≤40 kg: Not recommended. |
| Geriatric use | No specific dose adjustment; monitor for bradycardia and atrioventricular block due to age-related conduction system changes. Caution in patients ≥65 years due to limited data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FINGOLIMOD (FINGOLIMOD).
| Breastfeeding | Fingolimod is excreted in human breast milk. The milk-to-plasma ratio (M/P) is approximately 2:1. Based on a typical maternal dose, the estimated infant exposure is about 0.2-0.4% of the maternal weight-adjusted dose. Due to potential for serious adverse effects (immunosuppression, bradycardia), breastfeeding is not recommended during fingolimod therapy. |
| Teratogenic Risk | FDA Pregnancy Category C. Based on animal studies, fingolimod is associated with increased risk of fetal malformations, including persistent truncus arteriosus and ventricular septal defects, particularly during the first trimester. Human data are limited, but case reports suggest potential fetal harm. Contraindicated in pregnancy. Women of childbearing potential must use effective contraception during treatment and for 2 months after discontinuation. |
■ FDA Black Box Warning
Risk of serious infections; cases of fatal herpes infections (e.g., varicella zoster) reported. Requires baseline VZV serology and vaccination if negative.
| Serious Effects |
Patients with recent myocardial infarction (within 6 months), unstable angina, stroke, transient ischemic attack, decompensated heart failure, or history of Mobitz type II second-degree or third-degree AV block or sick sinus syndrome (unless pacemaker in place), severe active infections, and hypersensitivity to fingolimod or any of its excipients.
| Precautions | Bradyarrhythmia and AV block (monitor for 6 hours after first dose), increased infection risk (especially herpes viruses), macular edema (ophthalmologic exam at baseline and 3-4 months after initiation), progressive multifocal leukoencephalopathy (PML), posterior reversible encephalopathy syndrome (PRES), severe exacerbation of MS after discontinuation, respiratory effects (decline in FEV1 and DLCO), liver injury, fetal risk, blood pressure effects (hypertension), and risk of basal cell carcinoma. |
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| Fetal Monitoring | Before initiation: complete blood count, liver function tests, ophthalmic exam, ECG, and varicella zoster virus serology. During pregnancy: monthly CBC, LFTs, and blood pressure monitoring; fetal ultrasound to assess for cardiac anomalies; monitor for signs of infection. Postpartum: continued monitoring of infant for immunosuppression and cardiac effects. |
| Fertility Effects | In animal studies, fingolimod reduced fertility in female rats at clinically relevant doses. Human data are limited; potential for reversible impairment of spermatogenesis and ovulation. Weigh risk versus benefit in patients planning pregnancy. |