REMS restricted

Sparsentan

FILSPARI

Open Sparsentan in the interactive console ↗

Pronunciation: spar-SEN-tan (fil-SPAH-ree)

Sparsentan ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Sparsentan ballicule

Sparsentan FILSPARI mascot mnemonic cartoon — Visual mnemonic: Sparsentan mascot
**“Sparsely Filled spare”**
A sartan is hiding inside → dual ARB and endothelin receptor antagonist

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.

Sparsentan molecular structure (skeletal formula) — Molecular structure: Sparsentan

FDA-approved for

IgA nephropathy at risk of rapid progression (2023)

Classes and tags

Clinical profile

Therapeutic safety burden4 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk4 / 4

Legacy pregnancy categoryN/A (post-2015 labeling)

Defining liabilityHepatotoxicity, pregnancy contraindication and hypotension

FDA label

Read the full label on DailyMed ↗

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

Available strengths

tab 200, 400 mg

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)

Cost

Sparsentan (FILSPARI)

Strength		#/mo	generic $/mo	CostPlus
200 mg	tab	30 qd		not offered
400 mg	tab	30 qd		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Sparsentan is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Open Sparsentan in the interactive console ↗

Memory aids: interaction avatars

Box: minimal PK interactions

Open Sparsentan in the interactive console ↗

Self-check

Which two receptors does sparsentan block?
ETA and AT1.
Which organ toxicity is addressed by sparsentan’s REMS?
Hepatotoxicity.