Sparsentan

Sparsentan is a prescription medication used to reduce proteinuria in adults with primary immunoglobulin A nephropathy.

• Sparsentan is available under the following different brand names: Filspari

Common side effects of Sparsentan include:

• swelling of the hands, legs, ankles and feet,
• dizziness, and
• low red blood cells (anemia)

Serious side effects of Sparsentan include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• nausea,
• vomiting,
• stomach pain (upper right side),
• tiredness,
• loss of appetite,
• yellowing of the skin or eyes (jaundice),
• dark urine,
• fever,
• itching,
• serious birth defects,
• low blood pressure,
• dizziness,
• lightheadedness,
• fainting,
• muscle cramps,
• dry skin,
• shortness of breath,
• trouble sleeping,
• frequent urination,
• little or no urination,  
• abnormal blood test results (increased potassium),
• unusual weight gain, and
• swelling of the ankles or legs

Rare side effects of Sparsentan include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 200 mg
• 400 mg

IgA Nephropathy

Adult dosage

• 200 mg orally every day initially; after 14 days, increase to the recommended dose of 400 mg every day, as tolerated
• When resuming treatment after an interruption, consider starting at 200 mg/day, then after 14 days, increase to 400 mg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Sparsentan has severe interactions with the following drugs:
  • aliskiren
  • ambrisentan
  • aprocitentan
  • azilsartan
  • bosentan
  • candesartan
  • eprosartan
  • irbesartan
  • losartan
  • macitentan
  • olmesartan
  • sacubitril/valsartan
  • telmisartan
  • valsartan
• Sparsentan has serious interactions with at least 47 other drugs.
• Sparsentan has moderate interactions with at least 115 other drugs.
• Sparsentan has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Pregnant patients
• Administration with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or aliskiren

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sparsentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sparsentan?”

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 the diuretic dose, then consider modifying the 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 the 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 the 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 the blood pressure has stabilized
• Hepatotoxicity
  • Some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure
  • Elevated ALT/AST more than thrice the 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 and completing training
  • All patients must enroll in the FILSPARI REMS before initiating treatment and comply 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 is 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 increase 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 is 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 the 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 the 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 the 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 and Lactation

• 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
• 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