during treatment Interrupt treatment and closely monitor if aminotransferase elevations >3x ULN Avoid use in patients with elevated aminotransferases at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity Embryofetal toxicity Can cause major birth defects if used by pregnant patients, based on animal data Pregnancy testing is required before initiating treatment, during treatment, and 1 month after discontinuation Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for 1 month after discontinuation Contraindications Pregnant patients Administration with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren Cautions Based on animal data, can cause fetal harm when administered to pregnant females and is contraindicated during pregnancy Monitor serum potassium periodically and treat appropriately; dosage reduction or discontinuation of sparsentan may be required Fluid retention may occur with ERAs; if clinically significant fluid retention develops, evaluate to determine the cause and the potential need to initiate or modify diuretic dose, then consider modifying sparsentan dose Kidney injury Monitor kidney function periodically Drugs that inhibit the renin-angiotensin system (RAS) can cause acute kidney injury Caution in patients whose kidney function may depend in part on activity of RAS (eg, renal artery stenosis, chronic kidney disease, severe CHF, volume depletion) Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function Hypotension Hypotension observed in clinical trials In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status If hypotension develops despite elimination or reduction of other antihypertensive medications, consider dose reduction or dose interruption Transient hypotensive response is not a contraindication to further dosing, which can be given once blood pressure has stabilized Hepatotoxicity Some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure Elevated ALT/AST ≥3x ULN observed in treated patients, including cases confirmed with rechallenge Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment and seek medical attention If aminotransferase levels are abnormal at any time during treatment, interrupt dosing and monitor as recommended Requirements of the FILSPARI REMS Prescribers must be certified with the FILSPARI REMS by enrolling andcompleting training All patients must enroll in the FILSPARI REMS before initiating treatment andcomply with monitoring requirements Pharmacies must be certified with the FILSPARI REMS and must dispense only to patients who are authorized to receive therapy Additional information available at https://rems.filspari.com/ or 1-833-513-1325 Drug interaction overview Substrate of CYP3A (major) Inducer of CYP2B6, CYP2C9, CYP2C19 Inhibitor of P-gp and BCRP RAS inhibitors and ERAs Contraindicated Coadministration with RAS inhibitors, ERAs, or aliskiren is contraindicated owing to additive pharmacologic effects Strong CYP3A inhibitors Avoid coadministration Strong CYP3A inhibitors increases sparsentan peak plasma levels and AUC, which may increase adverse effects If use is unavoidable, interrupt treatment with sparsentan When resuming sparsentan, consider dose titration Moderate CYP3A inhibitors Monitor No dosage adjustment needed; monitor blood pressure, serum potassium, edema, and kidney function regularly if coadministered Strong CYP3A inducers Avoid Strong CYP3A inducers decrease sparsentan peak plasma levels and AUC, which may decrease efficacy Antacids Modify dosage schedule Sparsentan exhibits pH-dependent solubility Administer sparsentan 2 hr before or after administration of antacids Coadministration may decrease sparsentan exposure, which may reduce efficacy Acid-reducing agents Avoid Sparsentan exhibits pH-dependent solubility Coadministration with acid-reducing agents (eg, histamine H2 receptor antagonist, proton pump inhibitor [PPI]) may decrease sparsentan exposure, which may reduce efficacy NSAIDs (including COX-2 inhibitors) Monitor for signs of worsening renal function In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, coadministration of NSAIDs and selective COX-2 inhibitors with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure CYP2B6, 2C9, and 2C19 substrates Monitor for efficacy of substrate Consider dosage adjustment in accordance with the substrate’s prescribing information P-gp and BCRP substrates Avoid with sensitive P-gp and BCRP substrates Sparsentan is an inhibitor of P-gp and BCRP Agents increasing serum potassium Monitor serum potassium frequently Coadministration with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia Pregnancy Contraindicated in pregnant patients Based on animal data, can cause fetal harm, including birth defects and fetal death, when administered to pregnant females Verify patients of reproductive potential are not pregnant before initiating, monthly during treatment, and 1 month after discontinuing drug Advise pregnant patients of the potential risk to the fetus Animal studies Oral administration to pregnant rats throughout organogenesis at 10 times the maximum recommended human dose in mg/day caused teratogenic effects in rats, including craniofacial malformations, skeletal abnormalities, increased embryo-fetal lethality, and reduced fetal weights Contraception Patients of reproductive potential: Use an effective method of contraception before initiating, during treatment, and for 1 month after discontinuing Lactation Data are not available on presence of drug in human milk, effects on breastfed infants, or effect on milk production Owing to the potential for adverse reactions, such as hypotension in breastfed infants, advise patients not to breastfeed during treatment Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Dual endothelin angiotensin receptor antagonist (DEARA) Selectively blocks endothelin 1A receptors (ETAR) and angiotensin II type 1 receptors (AT1R) Endothelin-1 and angiotensin II are thought to contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN) via the ETAR and AT1R, respectively Absorption Peak plasma time: ~3 hr Peak plasma concentration, steady-state: 6.47 mcg/mL AUC, steady-state: 63.6 mcg⋅hr/mL Distribution Protein bound: >99% Vd: 61.4 L Metabolism CYP3A is major metabolic pathway Elimination Half-life: 9.6 hr Clearance: 5.11 L/hr Excretion: Feces 80% (9% unchanged); urine 2% (negligible amount unchanged) Oral Administration Swallow tablets whole with water before morning or evening meal Maintain same dosing pattern in relationship to meals Missed dose Take next dose at regularly scheduled time Do not take double or extra doses Storage Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) Store in its original container No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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