FILSPARI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FILSPARI (FILSPARI).
FILSPARI (sparsentan) is an endothelin receptor antagonist (ERA) and angiotensin II receptor blocker (ARB) with high affinity for the endothelin type A (ETA) receptor and angiotensin II type 1 (AT1) receptor. It reduces proteinuria in IgA nephropathy by inhibiting endothelin-1 mediated vasoconstriction, inflammation, and fibrosis, and by blocking angiotensin II mediated effects.
| Metabolism | Sparsentan is metabolized primarily by CYP3A4 and to a lesser extent by CYP2C8 and CYP2C9. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine. ~59% of dose recovered in feces and ~27% in urine as metabolites. |
| Half-life | Terminal half-life ~30 hours in healthy subjects, supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | Approximately 10 L (≈0.14 L/kg for a 70 kg adult), indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability ~57% under fasted conditions; reduced with high-fat meal. |
| Onset of Action | Not applicable; clinical effect (reduction in proteinuria) observed after weeks of continuous dosing. |
| Duration of Action | Sustained reduction in proteinuria over 24-hour dosing interval; clinical effect persists with continued treatment. |
| Molecular Weight | 478.5 |
200 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 200 mg once daily. eGFR <30 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: not recommended. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment; use caution due to age-related renal decline. |
| 1st trimester | Insufficient human data; based on animal studies, may cause fetal harm. Use only if benefit justifies risk. |
| 2nd trimester | Insufficient human data; based on animal studies, may cause fetal harm. Use only if benefit justifies risk. |
| 3rd trimester | Insufficient human data; based on animal studies, may cause fetal harm. Use only if benefit justifies risk. |
Clinical note
Comprehensive clinical and safety monograph for FILSPARI (FILSPARI).
| Placental transfer | Predicted to cross placenta based on molecular weight <500 Da and animal studies; specific human data not available. |
| Breastfeeding | No data on presence in human milk or effects on breastfed infant. Consider developmental and health benefits of breastfeeding along with mother's clinical need and potential adverse effects on infant. |
■ FDA Black Box Warning
WARNING: HEPATOTOXICITY. Sparsentan can cause serious and potentially fatal liver injury. Obtain baseline liver enzymes and monitor monthly for the first 12 months, then quarterly. Discontinue if liver enzyme elevation with symptoms or bilirubin >2x ULN.
| Serious Effects |
Hypersensitivity to sparsentan or any excipientConcomitant use with angiotensin receptor blockers, aliskiren in patients with diabetes, or strong CYP3A4 inducers
| Precautions | Hepatotoxicity; embryo-fetal toxicity (must exclude pregnancy before initiation and monthly during treatment); hypotension; acute kidney injury; hyperkalemia; fluid retention; edema; anemia; neutropenia. Monitor liver function, blood pressure, renal function, and potassium levels. |
| Food/Dietary | Grapefruit and grapefruit juice may increase sparsentan levels and are contraindicated. No other significant food interactions. Take with or without food. |
Loading safety data…
| Lactation Rating |
| L5 |
| Teratogenic Risk | Based on its mechanism of action as an endothelin receptor antagonist, FILSPARI is expected to be teratogenic. There are no adequate and well-controlled studies in pregnant women. In animal studies, endothelin receptor antagonists have caused teratogenicity, including craniofacial and cardiovascular malformations, at clinically relevant exposures. Use in pregnancy is contraindicated. Fetal risk is highest during the first trimester but may extend throughout pregnancy. |
| Fetal Monitoring | Pregnancy testing must be performed before initiation of treatment, monthly during treatment, and 1 month after discontinuation. Advise females of reproductive age to use effective contraception. Monitor liver function tests (ALT, AST, bilirubin) monthly due to hepatotoxicity risk. Monitor blood pressure regularly as FILSPARI may cause hypotension. Assess renal function periodically. |
| Fertility Effects | Endothelin receptor antagonists have been associated with testicular tubular atrophy and impaired spermatogenesis in animal studies, suggesting potential male fertility impairment. No human data are available. In females, effects on fertility are unknown; however, due to mechanism, potential for ovarian toxicity cannot be excluded. |
| Clinical Pearls | FILSPARI (sparsentan) is a dual endothelin angiotensin receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Monitor liver function tests (LFTs) at baseline and periodically due to risk of hepatotoxicity. Contraindicated in pregnancy; obtain pregnancy test before initiation and monthly thereafter. Check blood pressure regularly due to risk of hypotension, especially when co-administered with antihypertensives. Initiate at 200 mg orally once daily, titrate to 400 mg daily after 14 days as tolerated. Avoid use with strong CYP3A4 inhibitors or inducers; adjust dose with moderate CYP3A4 inhibitors. |
| Patient Advice | FILSPARI reduces protein in the urine but does not cure IgA nephropathy. · Take once daily with or without food; swallow tablet whole. · Do not use if you are pregnant or planning to become pregnant; use effective contraception during treatment and for 1 month after stopping. · Report symptoms of liver problems: yellow skin/eyes, dark urine, upper right stomach pain, or unusual tiredness. · Avoid grapefruit juice and grapefruit products while taking FILSPARI. · Keep all blood pressure and lab appointments to monitor liver function and pregnancy status. |