Filspari 400mg Tablets
WARNING: Severe liver problems may happen with this drug. This drug may not be right for patients who already have raised liver enzymes or liver problems. Tell your doctor if you have liver problems. You will need to have blood work checked before you start this drug and while you are taking it. If you have questions, talk with your doctor.Call your doctor right away if you have signs of liver problems like dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light- colored stools, throwing up, or yellow skin or eyes. Do not take this drug while you are pregnant. Use of this drug during pregnancy may cause birth defects or death of the unborn baby. You will need to have a pregnancy test to show that you are NOT pregnant before starting this drug, while you are taking it, and 1 month after you stop this drug. Talk with the doctor.If you may become pregnant, you must use birth control before starting this drug, while you are taking it, and for 1 month after you stop this drug. Talk with your doctor about what type(s) of birth control to use with this drug.If you have sex without using birth control, if you think you may be pregnant, or if you miss your period, call your doctor right away. @ COMMON USES: It is used to slow kidney problems getting worse in certain patients who have kidney disease.
Drug Class
Endothelin and Angiotensin II Receptor Antagonist
Pharmacologic Class
Dual Endothelin A and Angiotensin II Type 1 Receptor Antagonist (DEARA)
Pregnancy Category
Not applicable (contraindicated due to REMS)
FDA Approved
Feb 2023
DEA Schedule
Not Controlled
Overview
What is this medicine?
Filspari is a medication used to treat a specific kidney disease called IgA nephropathy. It helps to reduce the amount of protein in your urine, which can protect your kidneys from further damage. It works by blocking two different pathways in your body that contribute to kidney disease progression.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication at the same time every day, either before breakfast or before your evening meal. Swallow the tablet whole with a glass of water.
It's also important to stay hydrated by drinking plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake. However, avoid taking antacids within 2 hours before or 2 hours after taking your medication, as this can interfere with its effectiveness.
Storing and Disposing of Your Medication
Keep your medication in its original container and store it at room temperature in a dry place. Avoid storing it in the bathroom.
What to Do If You Miss a Dose
If you miss a dose, skip it and take your next dose at the usual time. Do not take two doses at the same time or take extra doses to make up for the missed one.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication at the same time every day, either before breakfast or before your evening meal. Swallow the tablet whole with a glass of water.
It's also important to stay hydrated by drinking plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake. However, avoid taking antacids within 2 hours before or 2 hours after taking your medication, as this can interfere with its effectiveness.
Storing and Disposing of Your Medication
Keep your medication in its original container and store it at room temperature in a dry place. Avoid storing it in the bathroom.
What to Do If You Miss a Dose
If you miss a dose, skip it and take your next dose at the usual time. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Do not become pregnant while taking this medication and for one month after stopping it. Use effective birth control methods.
- Attend all scheduled blood tests and doctor appointments to monitor your liver, potassium levels, and blood pressure.
- Report any signs of liver problems (e.g., yellow skin/eyes, dark urine, severe nausea/vomiting, unusual tiredness, stomach pain) or high potassium (e.g., muscle weakness, irregular heartbeat) immediately.
- Avoid grapefruit and grapefruit juice as they can interact with this medication.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
400 mg orally once daily
Dose Range:
400 - 400 mg
Condition-Specific Dosing:
IgA Nephropathy:
400 mg orally once daily
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (eGFR âĨ60 mL/min/1.73 m2)
Moderate:
No dose adjustment needed (eGFR 30 to <60 mL/min/1.73 m2)
Severe:
Not recommended (eGFR <30 mL/min/1.73 m2)
Dialysis:
Not recommended
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A)
Moderate:
Not recommended (Child-Pugh B)
Severe:
Not recommended (Child-Pugh C)
Pharmacology
Mechanism of Action
Sparsentan is a dual endothelin A (ETA) and angiotensin II type 1 (AT1) receptor antagonist. It blocks both the endothelin-1 and angiotensin II pathways, which are implicated in the progression of chronic kidney disease by promoting vasoconstriction, inflammation, fibrosis, and proteinuria.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified as a percentage, but well absorbed
Tmax:
3-4 hours
FoodEffect:
High-fat meal decreases Cmax by 35% and AUC by 20%. Can be taken with or without food, but consistency is recommended.
Distribution:
Vd:
Approximately 30 L
ProteinBinding:
>99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 10-13 hours
Clearance:
Not explicitly quantified
ExcretionRoute:
Primarily fecal (approximately 80%), with minor renal excretion (approximately 15%)
Unchanged:
Less than 1% renally excreted unchanged
Pharmacodynamics
OnsetOfAction:
Proteinuria reduction observed within weeks of initiation
PeakEffect:
Not explicitly defined for clinical effect
DurationOfAction:
24 hours (supports once-daily dosing)
Safety & Warnings
BLACK BOX WARNING
Hepatotoxicity: Sparsentan can cause liver injury. Measure ALT, AST, and total bilirubin prior to initiation of treatment and monthly for the first 12 months, and then quarterly thereafter. Embryo-Fetal Toxicity: Sparsentan can cause major birth defects. Contraindicated in pregnancy. Females of reproductive potential must have a negative pregnancy test prior to initiation of treatment, monthly during treatment, and 1 month after discontinuation of treatment. Females of reproductive potential must use effective contraception prior to initiation of treatment, during treatment, and for 1 month after discontinuation of treatment. Sparsentan is available only through a restricted program called the FILSPARI REMS Program.
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high potassium levels, including:
+ Abnormal heartbeat
+ Confusion
+ Weakness, lightheadedness, or dizziness
+ Feeling like passing out
+ Numbness or tingling
+ Shortness of breath
Signs of kidney problems, such as:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Severe dizziness or fainting
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
* Dizziness
Note: This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high potassium levels, including:
+ Abnormal heartbeat
+ Confusion
+ Weakness, lightheadedness, or dizziness
+ Feeling like passing out
+ Numbness or tingling
+ Shortness of breath
Signs of kidney problems, such as:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Severe dizziness or fainting
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people may not experience any side effects or only minor ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
* Dizziness
Note: This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Yellowing of your skin or the whites of your eyes (jaundice)
- Unusual darkening of your urine
- Severe nausea or vomiting
- Unusual tiredness or fatigue
- Pain in the upper right side of your stomach
- Muscle weakness or cramps
- Irregular heartbeat
- Dizziness or lightheadedness
- Fainting
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, depression, high blood pressure, and other conditions, may interact with this medication. Your doctor or pharmacist can advise you on which medications should not be taken with this drug.
If you are breastfeeding. It is recommended that you do not breastfeed while taking this medication.
Please note that this is not an exhaustive list of all potential drug interactions or health concerns that may affect your use of this medication. To ensure your safety, it is vital to:
Inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems.
Verify that it is safe to take this medication with all your other medications and health conditions.
Never start, stop, or change the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, depression, high blood pressure, and other conditions, may interact with this medication. Your doctor or pharmacist can advise you on which medications should not be taken with this drug.
If you are breastfeeding. It is recommended that you do not breastfeed while taking this medication.
Please note that this is not an exhaustive list of all potential drug interactions or health concerns that may affect your use of this medication. To ensure your safety, it is vital to:
Inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems.
Verify that it is safe to take this medication with all your other medications and health conditions.
Never start, stop, or change the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. To minimize the risk of dizziness or fainting, stand up slowly when getting up from a sitting or lying down position, and exercise caution when climbing stairs. Regularly undergo blood tests and blood pressure checks as directed by your doctor. If you consume grapefruit juice or eat grapefruit frequently, discuss this with your doctor. Additionally, if you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium supplement, consult with your doctor to ensure safe use of this medication.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well characterized but may include exaggerated adverse effects such as severe hypotension, hyperkalemia, or liver dysfunction.
What to Do:
In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention. Management should be supportive, including monitoring of vital signs, liver function, and electrolytes.
Drug Interactions
Contraindicated Interactions
- Angiotensin Receptor Blockers (ARBs)
- Angiotensin-Converting Enzyme (ACE) Inhibitors
- Aliskiren
- Strong CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir)
- OATP1B1/3 Inhibitors (e.g., cyclosporine, rifampin)
Major Interactions
- Moderate CYP3A4 Inhibitors (e.g., diltiazem, erythromycin, fluconazole)
- P-glycoprotein (P-gp) Inhibitors (e.g., amiodarone, verapamil, quinidine)
Moderate Interactions
- CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort)
- P-glycoprotein (P-gp) Inducers (e.g., rifampin, St. John's Wort)
- Potassium-sparing diuretics
- Potassium supplements
Minor Interactions
- Not specifically listed as minor interactions requiring specific action beyond general caution
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, total bilirubin)
Rationale: To establish baseline and monitor for drug-induced hepatotoxicity
Timing: Prior to initiation of treatment
Serum Potassium
Rationale: To establish baseline and monitor for hyperkalemia
Timing: Prior to initiation of treatment
Blood Pressure
Rationale: To establish baseline and monitor for hypotension
Timing: Prior to initiation of treatment
Pregnancy Test
Rationale: Sparsentan is contraindicated in pregnancy due to embryo-fetal toxicity; part of REMS program
Timing: Within one week prior to initiation of treatment for females of reproductive potential
Routine Monitoring
Liver Function Tests (ALT, AST, total bilirubin)
Frequency: Monthly for the first 12 months, then quarterly thereafter
Target: Within normal limits
Action Threshold: Discontinue if ALT or AST >3 x ULN with bilirubin >2 x ULN, or if ALT or AST >8 x ULN. Consider discontinuation if ALT or AST >5 x ULN.
Serum Potassium
Frequency: Monthly for the first 3 months, then quarterly thereafter
Target: 3.5-5.0 mEq/L
Action Threshold: Manage hyperkalemia according to clinical guidelines; consider dose interruption or discontinuation if severe or persistent.
Blood Pressure
Frequency: Regularly (e.g., at each clinic visit)
Target: Individualized, typically <130/80 mmHg
Action Threshold: Manage symptomatic hypotension; consider dose reduction or discontinuation if persistent or severe.
Pregnancy Test
Frequency: Monthly for females of reproductive potential
Target: Negative
Action Threshold: Discontinue sparsentan immediately if pregnancy is confirmed.
Symptom Monitoring
- Signs and symptoms of liver injury (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, jaundice, scleral icterus)
- Signs and symptoms of hyperkalemia (e.g., muscle weakness, fatigue, paresthesias, bradycardia, irregular heartbeat)
- Signs and symptoms of hypotension (e.g., dizziness, lightheadedness, fainting)
Special Patient Groups
Pregnancy
Contraindicated in pregnancy due to embryo-fetal toxicity. Females of reproductive potential must use effective contraception and have monthly negative pregnancy tests as part of the FILSPARI REMS Program.
Trimester-Specific Risks:
First Trimester:
High risk of major birth defects and embryo-fetal toxicity.
Second Trimester:
High risk of major birth defects and embryo-fetal toxicity.
Third Trimester:
High risk of major birth defects and embryo-fetal toxicity.
Lactation
It is not known if sparsentan is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment with sparsentan and for one month after the last dose.
Infant Risk:
Unknown, but potential for serious adverse effects.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (âĨ65 years) and younger patients. No specific dose adjustment is needed based on age alone, but monitor for age-related decline in renal or hepatic function.
Clinical Information
Clinical Pearls
- Filspari is the first non-immunosuppressive treatment approved specifically for IgA nephropathy to reduce proteinuria.
- Strict adherence to the FILSPARI REMS Program is mandatory due to the risks of hepatotoxicity and embryo-fetal toxicity.
- Patients must be educated on the importance of regular blood tests (liver function, potassium) and pregnancy tests.
- Concomitant use with ACE inhibitors, ARBs, or aliskiren is absolutely contraindicated due to increased risk of adverse events.
- Avoid strong CYP3A4 inhibitors and OATP1B1/3 inhibitors due to significant drug interactions.
- Monitor blood pressure regularly as hypotension can occur.
Alternative Therapies
- Angiotensin-Converting Enzyme (ACE) Inhibitors (e.g., lisinopril, ramipril) - used for proteinuria reduction, but not concurrently with sparsentan.
- Angiotensin Receptor Blockers (ARBs) (e.g., valsartan, losartan) - used for proteinuria reduction, but not concurrently with sparsentan.
- Corticosteroids (e.g., prednisone) - used for immunosuppression in IgA nephropathy.
- Immunosuppressants (e.g., mycophenolate mofetil, cyclophosphamide) - used in more severe or progressive IgA nephropathy.
- SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin) - emerging evidence for kidney protection in chronic kidney disease, including IgA nephropathy.
Cost & Coverage
Average Cost:
Typically high, ranging from $9,000 - $12,000+ per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization, often with step therapy)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.