REMS restricted

Sparsentan

FILSPARI

Open Sparsentan in the interactive console ↗

What it isDual endothelin ETA and angiotensin II AT1 antagonist; IgA nephropathy.

Why this oneBlocking both pathways reduces proteinuria more than an ARB alone.

What limits itHepatotoxicity and embryo-fetal toxicity under a REMS. Hyperkalemia and hypotension; CYP3A4-dependent.

FDA-approved for

IgA nephropathy at risk of rapid progression (2023)

FDA label

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BOXED WARNING Hepatotoxicity (REMS-restricted: transaminases/bilirubin at baseline then q3 months; interrupt if >3x ULN; avoid if baseline >3x ULN) and embryo-fetal toxicity (contraindicated in pregnancy; exclude pregnancy before starting; effective contraception during and 2 weeks after)

FDA dosing	Population	Start	Target	Max
IgA nephropathy (to slow kidney function decline)	Adults	200 mg QD x 14 days	400 mg QD	400 mg QD
Proteinuria reduction in FSGS	Adults & peds >=8 y, >50 kg	400 mg QD x 14 days	800 mg QD	800 mg QD
Proteinuria reduction in FSGS	Adults & peds >=8 y, <=50 kg	200 mg QD x 14 days	400 mg QD	400 mg QD

Titration 14 days at starting dose, then increase to recommended dose as tolerated; after interruption consider restarting at 50% dose and re-titrating after 14 days

Renal Undefined

Hepatic Avoid in any hepatic impairment (Child-Pugh A-C)

ALT/AST >3-8x ULN: confirm, interrupt, monitor at least weekly; resume at 50% dose only if asymptomatic and back to pretreatment levels. >8x ULN: permanently discontinue

Instructions

Discontinue RAAS inhibitors and ERAs before initiating
Swallow whole with water before the morning or evening meal (same meal daily)
If unable to swallow: crush, suspend in half cup water, take immediately (water only); do not store
Missed dose: take next dose at scheduled time; do not double
Avoid strong CYP3A inhibitors; interrupt sparsentan if unavoidable
REMS program: prescriber, patient, and pharmacy enrollment required; LFT monitoring q3 months
Exclude pregnancy before initiating; pregnancy testing per REMS

Contraindications

Pregnancy
Concomitant angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren

Cautions

Hepatotoxicity (ALT/AST >=3x ULN in up to 3.5%) — q3-month LFT monitoring; stop immediately for hepatotoxicity symptoms
Available only through FILSPARI REMS
Embryo-fetal toxicity — contraception during and 2 weeks after treatment
Hypotension incl. orthostatic — adjust other antihypertensives; reduce or interrupt dose if it persists
Acute kidney injury — monitor kidney function; risk higher with renal artery stenosis, CKD, severe CHF, volume depletion
Hyperkalemia — monitor potassium; risk higher with advanced kidney disease or potassium-increasing drugs
Fluid retention — evaluate and consider diuretic or dose modification

Adverse reactions

Hyperkalemia
Hypotension (incl. orthostatic)
Peripheral edema
Dizziness
Anemia
Acute kidney injury
Transaminase elevations

Pregnancy Contraindicated — may cause birth defects and fetal death (teratogenic in animals); exclude pregnancy before starting; contraception during and 2 weeks after

Lactation Do not breastfeed (potential for infant hypotension)

⚠ BOXED WARNINGS