Sparsentan

Sparsentan (brand name Filspari) is used to slow kidney function decline in adults with immunoglobulin A nephropathy (IgAN) at risk for disease progression or to reduce proteinuria in adults and children 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. Sparsentan works by blocking two substances, endothelin and angiotensin II, that are involved in kidney damage, reducing inflammation and protein in the urine (proteinuria).

Sparsentan is only available from a specialty pharmacy through a restricted program called Filspari REMS.

Sparsentan is a dual endothelin and angiotensin II receptor antagonist.

Sparsentan is a tablet taken once a day with water, before the morning or evening meal, at around the same time each day.

Sparsentan is FDA-approved to treat adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. It first received accelerated FDA approval on February 17, 2023, and was granted full approval on September 5, 2024.

• Full approval was based on long-term results from the PROTECT clinical trial (NCT03762850), which showed that sparsentan significantly slowed the decline in kidney function over two years compared with irbesartan.

Sparsentan is also FDA-approved to reduce proteinuria in adults and children 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. This approval was granted on April 13, 2026, making it the first and only medicine approved by the FDA for FSGS.

Sparsentan works by blocking two key pathways believed to drive kidney damage in IgAN, the endothelin-1 pathway and angiotensin II pathway.

More specifically, sparsentan is a dual-acting medicine that selectively blocks:

• the angiotensin II type 1 receptor (AT1R), and
• the endothelin-1 type A receptor (ETAR).

By blocking these receptors, sparsentan helps reduce inflammation and pressure within the kidneys, which in turn lowers the amount of protein leaking into the urine and may help protect kidney function over time.

Sparsentan belongs to the drug class called dual endothelin angiotensin receptor antagonists (DEARAs).

Sparsentan (Filspari) REMS is a safety program required by the Food and Drug Administration to manage the risk of liver problems while taking sparsentan.

• Under this program, liver testing is required before initiation of sparsentan, then every 3 months during treatment.
• REMS stands for Risk Evaluation and Mitigation Strategy.
• Under Filspari (Sparsentan) REMS, prescribers, patients, and pharmacies must enroll in the program.
• Sparsentan will be sent directly to you by a specialty pharmacy enrolled in the Filspari REMS Program.
• Your healthcare provider will give you the complete details.
• Further information is available at www.filsparirems.com or 1-833-513-1325.

Immunoglobulin A nephropathy (IgAN) is a rare autoimmune kidney disease in which a protein made by the immune system, called immunoglobulin A (IgA), builds up in the kidneys. This buildup causes inflammation and damage, which allows blood and protein to leak into the urine.

Over time, ongoing protein loss in the urine can signal active disease and may lead to progressive loss of kidney function, which may require maintenance dialysis or kidney transplantation.

Focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome is a kidney disease characterized by scarring in parts of some glomeruli (filters) that causes proteinuria (protein in urine) below the nephrotic range (generally <3.5 g/day) and usually without severe edema, high cholesterol, or severe low albumin. It often represents secondary FSGS (such as that caused by obesity, HIV, or genetic factors), frequently progressing more slowly than cases with nephrotic syndrome.

Sparsentan is usually taken once per day. Follow your doctor's dosing instructions very carefully.

Swallow the tablet whole with a full glass of water before a meal. Take it the same way each time. Drink plenty of liquids while you are taking sparsentan.

If you cannot swallow the tablet whole, you may crush sparsentan and mix it in water only right before you take it. Do not mix sparsentan with other liquids.

• Crush the sparsentan tablet in a clean pill crusher or mortar and pestle.
• Mix the crushed sparsentan in half a cup of water. The crushed medicine will not completely dissolve in the water.
• Drink all of the mixture right away.
• If any of the pieces are left in the cup, add a little more water to the cup, swirl to mix, and drink right away.
• Do not store the mixed solution for later use.

Your condition may get worse if you stop using sparsentan suddenly. Ask your doctor before stopping the medicine.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

You may need frequent medical tests, even if you have no symptoms.

You will need frequent blood tests to check your liver function, and your next dose may be delayed based on the results.

Store at room temperature away from moisture and heat. Store sparsentan in the original container.

Some drugs should not be used with sparsentan. Tell your healthcare provider if you take:

• nonsteroidal anti-inflammatory drugs (NSAIDs)
• potassium-containing medicines, potassium supplements, or salt substitutes containing potassium
• blood pressure medicines
• antacids, including histamine (H2) receptor blockers or proton pump inhibitor (PPI) medicines

Ask your healthcare provider or pharmacist if you are not sure if you take one of these medicines.

Also see the "What other drugs will affect sparsentan?" section.

Tell your doctor if you have ever had:

• high blood pressure;
• heart problems; or
• liver or kidney disease.

Pregnancy

Do not use this medicine if you are pregnant, as it can cause serious birth defects. You must use effective birth control while using sparsentan and for at least 2 weeks after your last dose. Tell your doctor if you become pregnant.

Ask your doctor about the best form of birth control while you are using sparsentan. See more about effective birth control options in the Medication Guide. You will need to have a negative pregnancy test before starting this treatment. You will need to take a pregnancy test during and after treatment with sparsentan.

Breastfeeding

Do not breastfeed while taking this medicine

Common sparsentan side effects

Common side effects of sparsentan are:

• Swelling of hands, legs, ankles, and feet (peripheral edema)
• Low red blood cell count (anemia)
• Dizziness
• Low blood pressure (hypotension)
• High blood potassium levels (hyperkalemia)
• Acute kidney injury

Serious side effects and boxed warnings

Sparsentan has a boxed warning for liver toxicity and serious birth defects. A boxed warning is the FDA's strongest warning for prescription medicines.

Liver Toxicity (Boxed Warning)

Sparsentan can affect your liver. Liver failure was not observed in people treated with Filspari in clinical studies, but some medicines that are like sparsentan can cause liver failure.

Your healthcare provider will do blood tests to check your liver before starting treatment, then every 3 months during treatment. Your healthcare provider may temporarily stop or permanently stop treatment with sparsentan if you have changes in your liver tests. Stop taking sparsentan and get immediate medical attention for:

• Nausea, vomiting, or stomach pain (upper right)
• Pain on the upper right side of your stomach
• Tiredness
• Loss of appetite
• Yellowing of your skin or the white part of your eyes (jaundice)
• Dark “tea-colored” urine
• Fever
• Itching.

Serious Birth Defects (Boxed Warning)

Sparsentan can cause serious birth defects if taken during pregnancy. You should not take sparsentan if you are pregnant.

• Patients who can become pregnant should have a negative pregnancy test before starting treatment with sparsentan.
• Patients who can become pregnant should use effective contraception before starting treatment, during treatment, and for two weeks after stopping treatment with sparsentan.
• You should not take sparsentan while pregnant and for 2 weeks after. You should not be pregnant when they start taking Filspari or become pregnant during treatment with
• Tell your healthcare provider right away if you miss a menstrual period or think you may be pregnant.

Other serious side effects and warnings

Low Blood Pressure: Low blood pressure is common during treatment with this medicine and can also be serious. Tell your healthcare provider if you feel dizzy, light-headed, or faint. Stay hydrated during treatment.

Worsening of Kidney Function: This is common during treatment with sparsentan and can also be serious. Your healthcare provider will check your kidney function during treatment with this medicine.

Increased Potassium in Your Blood: This is common during treatment with sparsentan and can also be serious. Your healthcare provider will check your potassium blood level during treatment.

Fluid Retention: Sparsentan can cause your body to hold too much water. Tell your healthcare provider right away if you have any unusual weight gain or swelling of your ankles or legs.

These are not all the possible side effects of sparsentan. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult Dose for Primary Immunoglobulin A Nephropathy:

Initial dose: 200 mg orally once a day for 14 daysMaintenance dose: Following the initial dose, increase to 400 mg orally once a day, as toleratedGeneral dosing information:

• Consider dose titration when resuming treatment after interruption: Start with the initial dose for 14 days, then increase to the recommended maintenance dose.
• Dose may need modification with liver problems or drug interactions.

Dose of sparsentan for FSGS

Weight > 50 kg

• Initial: 400 mg orally once daily
• After 14 days: Increase to 800 mg once daily if tolerated.

Weight ≤ 50 kg

• Initial: 200 mg orally once daily
• After 14 days: Increase to 400 mg once daily if tolerated.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Do not take potassium supplements or use salt substitutes, unless your doctor has told you to.

Do not take with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren.

Grapefruit may interact with sparsentan and cause side effects. Avoid consuming grapefruit products.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use, which may increase side effects or make the medicines less effective.

Avoid taking an antacid within 2 hours before or after you take sparsentan.

Do not take with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren.

Drug interactions occur with strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, antacids, acid-reducing agents, non-steroidal anti-inflammatory drugs (NSAIDs), CYP2B6, 2C9, and 2C19 substrates, sensitive P-gp and BCRP substrates, and agents increasing serum potassium.

Tell your doctor about all your current medicines. Many drugs can affect sparsentan, especially:

• blood pressure or heart medications;
• a diuretic or "water pill" that may increase blood potassium, such as spironolactone, triamterene, amiloride; or
• NSAIDs (nonsteroidal anti-inflammatory drugs) - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may affect sparsentan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.