Filspari (Sparsentan)
Dual Endothelin and Angiotensin Receptor Antagonist for IgA Nephropathy
Quick Facts About Filspari
Key Takeaways About Filspari
- First-in-class dual mechanism: Filspari is the first drug to simultaneously block both endothelin (ETA) and angiotensin (AT1) receptors, targeting two major pathways that drive kidney damage in IgA nephropathy
- Significant proteinuria reduction: In the PROTECT clinical trial, Filspari demonstrated superior reduction in proteinuria compared to the active comparator irbesartan, with benefits sustained over time
- Pregnancy is strictly contraindicated: Filspari must not be taken during pregnancy due to the risk of serious harm to the developing baby. Reliable contraception is required during treatment and for 1 month after stopping
- Cannot be combined with ARBs, ERAs, or renin inhibitors: Due to overlapping mechanisms, Filspari must not be used alongside angiotensin receptor blockers, endothelin receptor antagonists, or aliskiren
- Regular monitoring is essential: Blood pressure, kidney function (creatinine), potassium levels, and liver function must be monitored throughout treatment, particularly during the initial weeks
What Is Filspari and What Is It Used For?
Filspari (sparsentan) is a prescription medication used to treat primary immunoglobulin A nephropathy (IgA nephropathy, IgAN) in adults who have a urine protein excretion of 1.0 g/day or more. It works by blocking two key receptor systems – endothelin and angiotensin – that are involved in regulating kidney function and contribute to kidney damage in IgAN.
IgA nephropathy, also known as Berger’s disease, is the most common form of primary glomerulonephritis worldwide. It is a chronic kidney disease caused by the immune system producing defective versions of an antibody called immunoglobulin A (IgA). These abnormal IgA antibodies accumulate in clusters within the tiny blood-filtering units of the kidney known as glomeruli. This accumulation triggers inflammation and progressive damage to the glomeruli, causing blood and protein to leak into the urine – a condition known as proteinuria.
Proteinuria is one of the most important predictors of disease progression in IgA nephropathy. Higher levels of protein in the urine are associated with a greater risk of progressive kidney function decline, which can ultimately lead to end-stage kidney disease (ESKD) requiring dialysis or kidney transplantation. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, reducing proteinuria is a primary therapeutic goal in managing IgA nephropathy, as sustained reductions in urine protein levels are associated with better long-term kidney outcomes.
Filspari contains the active substance sparsentan, which represents a novel pharmacological approach. It is a dual endothelin type A (ETA) and angiotensin II type 1 (AT1) receptor antagonist, meaning it simultaneously blocks two different hormone receptor systems in a single molecule. Endothelin-1 and angiotensin II are both potent vasoconstrictors (substances that narrow blood vessels) and pro-inflammatory mediators that play critical roles in the pathophysiology of kidney disease. In IgA nephropathy, these hormones contribute to glomerular hypertension (increased pressure within the kidney’s filtering units), inflammation, fibrosis (scarring), and progressive kidney damage.
By blocking both the ETA and AT1 receptors, Filspari reduces intraglomerular pressure, decreases inflammation, and limits fibrotic remodelling within the kidney. This dual action results in a greater reduction in proteinuria compared to single-pathway blockade with a standard angiotensin receptor blocker (ARB) alone. The PROTECT trial, a pivotal Phase III randomised controlled study, demonstrated that sparsentan achieved significantly greater proteinuria reduction compared to irbesartan (an established ARB) at 36 weeks, with sustained benefits through to 110 weeks of follow-up.
Filspari was approved by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) based on the PROTECT trial results. It represents the first treatment specifically developed and approved for IgA nephropathy that targets the endothelin pathway alongside the renin-angiotensin system. Previously, the standard of care relied primarily on supportive measures such as ACE inhibitors or ARBs alone.
What Should You Know Before Taking Filspari?
Before starting Filspari, your doctor needs to know about all your medical conditions, particularly if you have low blood pressure, impaired kidney or liver function, or if you are pregnant or planning to become pregnant. Filspari is strictly contraindicated during pregnancy and must not be combined with certain blood pressure medications.
Contraindications
You must not take Filspari if any of the following apply to you:
- Allergy to sparsentan or any other ingredient in the medicine (listed in the composition section below)
- Pregnancy, suspected pregnancy, or planning to become pregnant – Filspari can cause serious harm to the developing baby (see Pregnancy and Breastfeeding section)
- Concomitant use with angiotensin receptor blockers (ARBs) such as irbesartan, losartan, valsartan, candesartan, or telmisartan – Filspari already blocks the angiotensin receptor, and combining it with another ARB would cause dangerous double-blockade of the renin-angiotensin system
- Concomitant use with endothelin receptor antagonists (ERAs) such as bosentan, ambrisentan, macitentan, or sitaxentan – Filspari already blocks the endothelin receptor, and combining it with another ERA could lead to excessive blood pressure lowering and other serious adverse effects
- Concomitant use with renin inhibitors such as aliskiren – the combination increases the risk of hypotension, hyperkalaemia, and kidney impairment
Filspari must never be taken during pregnancy. Drugs that block the angiotensin system and the endothelin system are known to cause serious developmental harm to the unborn child, including birth defects, kidney failure, and death. If you discover you are pregnant while taking Filspari, stop taking it immediately and contact your doctor. Women of childbearing potential must use reliable contraception during treatment and for at least 1 month after stopping Filspari.
Warnings and Precautions
Talk to your doctor or pharmacist before taking Filspari if you have or have had any of the following conditions:
- Low blood pressure (hypotension) – Filspari can further lower blood pressure, which is particularly common in elderly patients. Your doctor may need to monitor your blood pressure more closely and may adjust your dose or temporarily stop Filspari if your blood pressure drops too low
- Impaired kidney function – since Filspari affects kidney haemodynamics, your doctor will perform additional tests to monitor how well your kidneys are functioning, particularly by measuring creatinine and potassium levels in your blood. A temporary decrease in kidney function may occur at the start of treatment
- Fluid retention (oedema) – if you develop swelling in your hands, ankles, or feet due to fluid build-up, your doctor may prescribe a diuretic (water tablet) or adjust your Filspari dose
- Liver problems – your doctor will order blood tests before starting treatment and at regular intervals during treatment to ensure your liver is functioning properly. Signs of liver dysfunction include nausea, vomiting, fever, abdominal pain, yellowing of the skin or eyes (jaundice), dark-coloured urine, skin itching, unusual tiredness or exhaustion, and flu-like symptoms with joint and muscle pain. If you notice any of these symptoms, contact your doctor immediately
Use in Children and Adolescents
Filspari is not recommended for children and adolescents under 18 years of age, as it has not been studied in this age group. The safety and efficacy of sparsentan in paediatric patients have not been established, and no data are available from clinical trials in this population. If IgA nephropathy is diagnosed in a young person, your doctor will discuss alternative treatment options based on the available evidence and current KDIGO guidelines for paediatric patients.
Pregnancy and Breastfeeding
Pregnancy: You must not take Filspari if you are pregnant, think you may be pregnant, or are planning to become pregnant. Sparsentan can cause serious harm to the unborn child. Both endothelin receptor antagonists and angiotensin receptor blockers are known teratogens (substances that cause birth defects) in humans. If you are a woman of childbearing potential, your doctor will require a negative pregnancy test before prescribing Filspari. You must use reliable contraception while taking Filspari and for at least 1 month after your last dose. If you become pregnant or suspect you may be pregnant during or shortly after treatment, stop taking Filspari immediately and seek urgent medical advice.
Breastfeeding: It is not known whether sparsentan or its metabolites pass into human breast milk. Due to the potential for serious adverse effects in the nursing infant, breastfeeding is not recommended during treatment with Filspari. Discuss the risks and benefits with your doctor before making any decisions about breastfeeding.
Driving and Operating Machinery
Filspari may cause side effects such as dizziness, which could impair your ability to drive or use machines safely. If you experience dizziness or any other symptom that affects your concentration, wait until these effects have resolved before driving a vehicle or operating machinery. This is particularly important at the start of treatment or after a dose increase.
Important Information About Some Ingredients
Filspari film-coated tablets contain lactose. If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine. The tablets also contain less than 1 mmol (23 mg) of sodium per tablet, meaning they are essentially sodium-free and are not expected to have any clinically significant effect related to sodium intake.
How Does Filspari Interact with Other Drugs?
Filspari has important interactions with several classes of medications, including blood pressure drugs, antifungals, certain antibiotics, HIV treatments, immunosuppressants, and herbal products. Some combinations are strictly prohibited, while others require careful monitoring. Always inform your doctor about all medications you are taking.
Sparsentan is metabolised primarily by the liver enzymes CYP3A4 and CYP2C8. Drugs that inhibit these enzymes can increase sparsentan blood levels (potentially causing more side effects), while drugs that induce these enzymes can decrease sparsentan levels (potentially reducing its effectiveness). Additionally, because Filspari blocks both endothelin and angiotensin receptors, combining it with other drugs that affect these same pathways is contraindicated.
Contraindicated Combinations
| Drug / Class | Examples | Reason |
|---|---|---|
| Angiotensin Receptor Blockers (ARBs) | Irbesartan, losartan, valsartan, candesartan, telmisartan | Double blockade of the renin-angiotensin system – risk of severe hypotension, hyperkalaemia, and acute kidney injury |
| Endothelin Receptor Antagonists (ERAs) | Bosentan, ambrisentan, macitentan, sitaxentan | Double blockade of the endothelin system – excessive vasodilation and risk of severe hypotension |
| Renin Inhibitors | Aliskiren | Triple RAAS blockade – significantly increased risk of hypotension, hyperkalaemia, and renal failure |
Combinations Requiring Caution
| Drug / Class | Effect | Recommendation |
|---|---|---|
| ACE inhibitors (enalapril, lisinopril) | Increased risk of hypotension, hyperkalaemia, and worsened kidney function | Use with caution under medical supervision; monitor blood pressure, potassium, and creatinine regularly |
| Mineralocorticoid receptor antagonists (spironolactone, eplerenone) | May increase potassium levels in the blood | Monitor potassium levels closely; avoid potassium supplements if possible |
| Potassium supplements / potassium-sparing diuretics | Increased risk of dangerously high potassium levels (hyperkalaemia) | Avoid concurrent use unless medically necessary; monitor potassium frequently |
| Azole antifungals (itraconazole, fluconazole) | CYP3A4 inhibitors that increase sparsentan blood levels | Monitor for increased side effects; dose adjustment may be necessary |
| Macrolide antibiotics (clarithromycin, erythromycin) | CYP3A4 inhibitors that increase sparsentan blood levels | Monitor blood pressure and side effects during concurrent use |
| Immunosuppressants (cyclosporine, tacrolimus) | May increase sparsentan blood levels; complex pharmacokinetic interaction | Close monitoring of drug levels and kidney function required |
Drugs That May Reduce Filspari’s Effectiveness
The following drugs are known inducers of CYP3A4 and can reduce the blood levels and clinical effectiveness of Filspari. If you are taking any of these medications, your doctor may need to consider alternative treatments or adjust your therapy:
- Rifampicin – used for tuberculosis and certain other bacterial infections
- Efavirenz – used for HIV treatment
- Carbamazepine, phenytoin, phenobarbital – antiepileptic drugs
- St. John’s Wort (Hypericum perforatum) – a herbal remedy used for mild depression and anxiety
- Dexamethasone – a corticosteroid used primarily for inflammation
Drugs That May Increase Filspari’s Effect
The following drugs are potent CYP3A4 inhibitors and can increase sparsentan blood levels, potentially leading to a greater risk of side effects. Your doctor should be informed if you are taking any of these:
- Boceprevir, telaprevir – used for hepatitis C treatment
- Conivaptan – used for low sodium levels in the blood
- Indinavir, lopinavir/ritonavir, nelfinavir, ritonavir – HIV protease inhibitors
- Nefazodone – an antidepressant
- Cyclosporine, tacrolimus – immunosuppressants used to prevent transplant rejection
Food and Drink Interactions
Grapefruit and grapefruit juice must not be consumed while taking Filspari. Grapefruit is a known inhibitor of CYP3A4, the primary enzyme involved in the metabolism of sparsentan. Consuming grapefruit or grapefruit juice while taking Filspari can lead to unpredictably elevated drug levels in the blood, increasing the risk of side effects such as excessive blood pressure lowering, dizziness, and fluid retention. Filspari can be taken with or without other foods.
What Is the Correct Dosage of Filspari?
The recommended starting dose of Filspari is 200 mg taken once daily as a single tablet. After 14 days, your doctor may increase the dose to 400 mg once daily depending on how well you tolerate the medication. Swallow the tablet whole with a glass of water.
Always take Filspari exactly as your doctor has instructed. Do not change your dose or stop taking Filspari without consulting your doctor first. The dosage is carefully individualised based on your tolerance, blood pressure response, kidney function, and any side effects you may experience.
Adults
Standard Adult Dosing
Starting dose: 200 mg (one tablet) taken once daily by mouth.
Titration: After 14 days, your doctor may increase the dose to 400 mg (either two 200 mg tablets or one 400 mg tablet) taken once daily, depending on your tolerability.
Administration: Swallow the tablet whole to avoid a bitter taste. Take with a glass of water. The tablet can be taken with or without food, but should ideally be taken at the same time each day.
| Phase | Dose | Duration | Notes |
|---|---|---|---|
| Initial | 200 mg once daily | First 14 days | Monitor blood pressure and tolerability |
| Maintenance | 400 mg once daily | Long-term | Increase only if 200 mg is well tolerated; can use two 200 mg tablets or one 400 mg tablet |
Children and Adolescents
Filspari has not been studied in patients under 18 years of age and is therefore not recommended in this population. There is no established paediatric dose for sparsentan. If IgA nephropathy is diagnosed in a child or adolescent, the treating nephrologist will determine the most appropriate treatment based on available evidence and current KDIGO paediatric guidelines.
Elderly Patients
There is no specific dose adjustment required for elderly patients based solely on age. However, elderly patients are more likely to have reduced kidney and liver function, lower blood pressure at baseline, and may be taking multiple medications that could interact with Filspari. Your doctor may start with particular caution, monitoring blood pressure more frequently and adjusting the dose as needed. Low blood pressure (hypotension) is more commonly reported in older adults taking Filspari.
Missed Dose
If you forget to take a dose of Filspari, skip the missed dose and take your next dose at the usual scheduled time. Do not take a double dose to make up for a forgotten dose. If you frequently forget doses, consider setting a daily alarm or using a pill organiser to help you remember.
Overdose
If you take more Filspari tablets than prescribed, or if someone (such as a child) accidentally ingests the medicine, contact a doctor or your local poison control centre immediately for risk assessment and advice. Bring the medicine packaging with you. Taking more than the prescribed dose may cause signs and symptoms of excessively low blood pressure, including severe dizziness, light-headedness, fainting, and rapid heartbeat. In a hospital setting, treatment is supportive and may include intravenous fluids and close monitoring of blood pressure and heart function.
What Are the Side Effects of Filspari?
Like all medicines, Filspari can cause side effects, although not everyone experiences them. The most common side effect is low blood pressure (hypotension), occurring in more than 1 in 10 patients. Other common side effects include dizziness, high potassium levels, fluid retention, fatigue, and changes in kidney or liver function.
The following side effects have been reported in clinical trials and post-marketing surveillance. The frequency categories are defined according to the European Medicines Agency convention:
Very Common
Affects more than 1 in 10 people
- Low blood pressure (hypotension) – you may feel light-headed or dizzy, particularly when standing up. This is the most frequently reported side effect and is often dose-dependent. Your doctor will monitor your blood pressure regularly, especially at the start of treatment and after dose increases
Common
Affects up to 1 in 10 people
- Orthostatic hypotension – dizziness or light-headedness when standing up or sitting up due to a drop in blood pressure. This is more likely to occur at the start of treatment. Rise slowly from lying or sitting positions to minimise this effect
- Dizziness – a general feeling of unsteadiness or light-headedness that may affect your ability to drive or operate machinery
- Hyperkalaemia – elevated potassium levels in the blood. This can be dangerous if severe and is monitored through regular blood tests. Symptoms of high potassium may include muscle weakness, fatigue, and irregular heartbeat
- Oedema (fluid retention) – swelling, particularly in the ankles and feet, caused by fluid accumulation in the body tissues. Your doctor may prescribe a diuretic to help manage this or may adjust your Filspari dose
- Fatigue (weakness) – unusual tiredness or lack of energy
- Decreased kidney function – particularly at the start of treatment, measured as an increase in serum creatinine. This is often a haemodynamic effect and may partially reverse over time. Your doctor will monitor your kidney function through regular blood and urine tests
- Acute kidney injury – a sudden decline in kidney function, primarily reported when treatment is first started. Close monitoring is essential during the initial weeks of therapy
- Elevated blood creatinine – creatinine is a waste product from muscle metabolism that is normally cleared by the kidneys. An increase indicates the kidneys may not be filtering as efficiently
- Headache – a common side effect that usually improves as your body adjusts to the medication
- Changes in liver function tests – your doctor will perform regular blood tests to monitor your liver. In most cases, these changes are mild and reversible
Uncommon
Affects up to 1 in 100 people
- Anaemia – low levels of red blood cells, which may cause tiredness, pale skin, and shortness of breath. Your doctor may check your blood count as part of routine monitoring
Contact your doctor or go to the nearest emergency department immediately if you experience: severe dizziness or fainting, signs of a serious allergic reaction (swelling of the face, lips, tongue, or throat; difficulty breathing), signs of liver problems (yellowing of the skin or eyes, dark urine, unexplained nausea and vomiting), or sudden and significant reduction in urine output. These symptoms may require urgent medical intervention.
Reporting suspected side effects after a medicine has been authorised is important. It allows continued monitoring of the medicine’s benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national medicines regulatory authority.
How Should You Store Filspari?
Store Filspari at room temperature with no special storage requirements. Keep out of sight and reach of children. Do not use after the expiry date printed on the carton and label.
Filspari has no special storage conditions. Keep the tablets in their original packaging to protect them from environmental factors. Store the medicine out of the sight and reach of children at all times. Do not use Filspari after the expiry date (EXP) stated on the carton and container label – the expiry date refers to the last day of that month.
Do not dispose of medicines via the household waste or down the drain. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help protect the environment and prevent accidental exposure.
What Does Filspari Contain?
The active ingredient in Filspari is sparsentan, available as 200 mg and 400 mg film-coated tablets. The tablets also contain several inactive ingredients including lactose and a small amount of sodium.
Active Ingredient
Each Filspari 200 mg film-coated tablet contains 200 mg sparsentan. Each Filspari 400 mg film-coated tablet contains 400 mg sparsentan.
Inactive Ingredients (Excipients)
The other ingredients are: microcrystalline cellulose, lactose, sodium starch glycolate (type A), colloidal anhydrous silica, magnesium stearate, poly(vinyl alcohol), macrogol, talc, and titanium dioxide (E171).
Tablet Appearance
| Strength | Appearance | Imprint | Packaging |
|---|---|---|---|
| 200 mg | White to off-white, oval, film-coated tablet (~13 mm × 7 mm) | “105” on one side | Bottle of 30 tablets |
| 400 mg | White to off-white, oval, film-coated tablet (~18 mm × 8 mm) | “021” on one side | Bottle of 30 tablets; multipack of 90 tablets (3 × 30) |
Not all pack sizes may be marketed in your country. The marketing authorisation holder is Vifor France, 100–101 Terrasse Boieldieu, Tour Franklin La Défense 8, 92042 Paris La Défense Cedex, France.
Frequently Asked Questions About Filspari
Filspari (sparsentan) is used to treat primary immunoglobulin A nephropathy (IgA nephropathy or IgAN) in adults who have significant protein in their urine (proteinuria of 1.0 g/day or more, or a urine protein/creatinine ratio of 0.75 g/g or higher). IgA nephropathy is a chronic kidney disease caused by defective IgA antibodies that accumulate in the kidney’s filtering units. Filspari helps reduce the protein leaking into the urine and slows the progression of the disease by blocking two key hormone receptors – endothelin and angiotensin – that contribute to kidney damage.
Filspari is the first drug to simultaneously block both endothelin type A (ETA) and angiotensin II type 1 (AT1) receptors in a single molecule. Traditional supportive therapy for IgA nephropathy typically relies on ACE inhibitors or angiotensin receptor blockers (ARBs), which only target the renin-angiotensin system. By blocking the endothelin pathway as well, Filspari addresses an additional mechanism of kidney injury – the endothelin system’s contribution to inflammation, vasoconstriction, and fibrosis. In the pivotal PROTECT trial, this dual mechanism resulted in significantly greater proteinuria reduction compared to the ARB irbesartan.
The most common side effect of Filspari is low blood pressure (hypotension), which affects more than 1 in 10 patients. Other frequently reported side effects include dizziness (including upon standing), elevated potassium levels in the blood, fluid retention with swelling of the ankles and feet, fatigue, decreased kidney function (especially early in treatment), elevated creatinine, headache, and changes in liver function tests. Anaemia has been reported less commonly. Most side effects are manageable with dose adjustment or additional medication, and regular monitoring by your doctor is essential throughout treatment.
No, Filspari is strictly contraindicated during pregnancy. Both endothelin receptor antagonists and angiotensin receptor blockers are known to cause serious harm to the developing baby. Women of childbearing potential must have a negative pregnancy test before starting treatment and must use reliable contraception throughout treatment and for at least 1 month after stopping Filspari. If pregnancy occurs during treatment, Filspari must be discontinued immediately and you should contact your doctor urgently. Breastfeeding is also not recommended because it is unknown whether sparsentan passes into breast milk.
Filspari must not be taken with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or renin inhibitors (such as aliskiren), as these combinations are contraindicated. However, Filspari can be used alongside ACE inhibitors (such as enalapril or lisinopril) under careful medical supervision, although this combination carries an increased risk of low blood pressure, high potassium, and worsened kidney function. Mineralocorticoid receptor antagonists (such as spironolactone) also require caution due to the risk of hyperkalaemia. Always discuss all your medications with your doctor before starting Filspari.
In the PROTECT clinical trial, measurable reductions in proteinuria were observed as early as 4 weeks after starting Filspari, with continued improvement over the following months. Significant proteinuria reduction was demonstrated at 36 weeks, and benefits were sustained through 110 weeks of treatment. However, the primary goal of Filspari therapy is to slow the long-term progression of IgA nephropathy, which is assessed over months to years of continuous treatment. Regular follow-up with your nephrologist, including urine protein and kidney function monitoring, is essential to assess your response to treatment.
References
- European Medicines Agency (EMA). Filspari (sparsentan) – Summary of Product Characteristics. Available at: ema.europa.eu
- Heerspink HJL, et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial (PROTECT). The Lancet. 2023;401(10388):1584–1594. doi:10.1016/S0140-6736(23)00569-X
- Rovin BH, et al. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International. 2021;100(4S):S1–S276. doi:10.1016/j.kint.2021.05.021
- U.S. Food and Drug Administration (FDA). Filspari Prescribing Information. Available at: fda.gov
- Wyatt RJ, Julian BA. IgA nephropathy. New England Journal of Medicine. 2013;368(25):2402–2414. doi:10.1056/NEJMra1206793
- Rodrigues JC, et al. IgA nephropathy. Clinical Journal of the American Society of Nephrology. 2017;12(4):677–686. doi:10.2215/CJN.07420716
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd edition, 2023. Available at: who.int
- Komers R, et al. Dual inhibition of endothelin and angiotensin II receptors with sparsentan: rationale and treatment effects in IgA nephropathy. Nephrology Dialysis Transplantation. 2023;38(Suppl 1):i37–i44. doi:10.1093/ndt/gfad063
Editorial Team
iMedic Medical Editorial Team – Specialists in Nephrology and Clinical Pharmacology. All content is based on peer-reviewed clinical evidence and current international guidelines.
iMedic Medical Review Board – Independent panel of board-certified physicians who verify the accuracy and clinical relevance of all medical content according to KDIGO, EMA, and WHO guidelines.
This article was last medically reviewed on . All information is evidence-based and reviewed following the GRADE framework. iMedic operates independently with no commercial funding or pharmaceutical industry sponsorship.