Filspari 200mg 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 Receptor Antagonist
Pharmacologic Class
Dual Endothelin Angiotensin Receptor Antagonist (DEARA)
Pregnancy Category
Not applicable (contraindicated due to embryo-fetal toxicity)
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 (IgAN). It works by blocking two different natural substances in your body that can harm your kidneys. By blocking these substances, Filspari helps to reduce the amount of protein that leaks into your urine, which is a sign of kidney damage in IgAN.
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 your morning or evening meal. It's essential to take it before the same meal every day to maintain a consistent routine.
When taking your medication, swallow the tablet whole with a glass of water. Stay hydrated by drinking plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Important Interactions to Avoid
Do not take antacids within 2 hours before or 2 hours after taking your medication, as this can interfere with its absorption.
Storing and Disposing of Your Medication
Keep your medication in its original container, stored at room temperature in a dry place. Avoid storing it in a bathroom, where the humidity and temperature can affect the medication's potency.
What to Do if You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule. 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 your morning or evening meal. It's essential to take it before the same meal every day to maintain a consistent routine.
When taking your medication, swallow the tablet whole with a glass of water. Stay hydrated by drinking plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Important Interactions to Avoid
Do not take antacids within 2 hours before or 2 hours after taking your medication, as this can interfere with its absorption.
Storing and Disposing of Your Medication
Keep your medication in its original container, stored at room temperature in a dry place. Avoid storing it in a bathroom, where the humidity and temperature can affect the medication's potency.
What to Do if You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Filspari on an empty stomach, at least 1 hour before your first meal or 2 hours after your last meal.
- Do not take this medication if you are pregnant or plan to become pregnant. Use effective birth control during treatment and for one month after stopping the medication.
- Do not breastfeed while taking Filspari.
- Attend all scheduled blood tests for kidney function, potassium levels, and liver function, as these are very important for your safety.
- Avoid grapefruit and grapefruit juice, as they can interact with this medication.
- Discuss all other medications, supplements, and herbal products you are taking with your doctor, especially potassium supplements, salt substitutes containing potassium, and certain pain relievers (NSAIDs).
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 200 mg orally once daily. After 14 days, increase to 400 mg orally once daily.
Dose Range:
200 - 400 mg
Condition-Specific Dosing:
IgA_Nephropathy:
Initial dose 200 mg orally once daily. After 14 days, increase to 400 mg orally once daily. Take at least 1 hour before the first meal of the day or 2 hours after the last meal of the day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required (eGFR 60-89 mL/min/1.73 m^2)
Moderate:
No dose adjustment required (eGFR 30-59 mL/min/1.73 m^2)
Severe:
Not recommended (eGFR <30 mL/min/1.73 m^2)
Dialysis:
Not recommended for patients with End-Stage Renal Disease (ESRD) or on dialysis.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A)
Moderate:
Not recommended (Child-Pugh B)
Severe:
Not recommended (Child-Pugh C)
Pharmacology
Mechanism of Action
Sparsentan is a dual endothelin and angiotensin II receptor antagonist. It selectively blocks both the endothelin A (ETA) receptor and the angiotensin II type 1 (AT1) receptor. By blocking these receptors, sparsentan is thought to reduce proteinuria in IgA nephropathy (IgAN) by mitigating endothelin- and angiotensin II-mediated pathways that contribute to kidney injury, inflammation, and fibrosis.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 50% (relative bioavailability)
Tmax:
3-4 hours
FoodEffect:
A high-fat meal decreases Cmax by 30% and AUC by 20%. Should be taken on an empty stomach.
Distribution:
Vd:
Approximately 30 L
ProteinBinding:
>99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 10-13 hours
Clearance:
Not explicitly stated as a single value, but primarily hepatic metabolism and biliary excretion.
ExcretionRoute:
Primarily feces (approximately 83%), with a smaller portion in urine (approximately 15%).
Unchanged:
Approximately 1% (in urine)
Pharmacodynamics
OnsetOfAction:
Reduction in proteinuria observed within weeks of initiation.
PeakEffect:
Maximal proteinuria reduction typically observed after several months of treatment.
DurationOfAction:
Sustained effect with once-daily dosing due to half-life.
Safety & Warnings
BLACK BOX WARNING
EMBRYO-FETAL TOXICITY: Do not administer Filspari to pregnant females. May cause major birth defects. Females of reproductive potential must use effective contraception prior to treatment, during treatment, and for 1 month after the last dose. HEPATOTOXICITY: May cause liver injury. Measure liver enzymes and bilirubin prior to initiation, monthly for 12 months, and quarterly thereafter. Discontinue if liver injury occurs.
Side Effects
Serious Side Effects: Seek Medical Help 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 attention 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 urinate
+ 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 do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
* Dizziness
Note: This is not an exhaustive list of all 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 attention 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 urinate
+ 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 do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
* Dizziness
Note: This is not an exhaustive list of all 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:
- Signs of liver problems: unusual tiredness, nausea, vomiting, stomach pain, dark urine, yellowing of the skin or eyes (jaundice).
- Signs of high potassium: muscle weakness, tiredness, numbness or tingling, slow or irregular heartbeat.
- Signs of low blood pressure: dizziness, lightheadedness, fainting.
- Signs of worsening kidney function: swelling in your hands, ankles, or feet; decreased urination.
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, should not be taken with this drug. Your doctor or pharmacist can help you determine if any of your current medications are incompatible 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 interactions between this medication and other substances. To ensure your safety, it is vital to discuss all of your medications, health problems, and concerns with your doctor and pharmacist. Before starting, stopping, or changing the dose of any medication, including this one, always consult with your doctor to confirm that it is safe to do so.
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, should not be taken with this drug. Your doctor or pharmacist can help you determine if any of your current medications are incompatible 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 interactions between this medication and other substances. To ensure your safety, it is vital to discuss all of your medications, health problems, and concerns with your doctor and pharmacist. Before starting, stopping, or changing the dose of any medication, including this one, always consult with your doctor to confirm that it is safe to do so.
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. As directed by your doctor, regularly undergo blood tests and blood pressure checks to monitor your condition. If you consume grapefruit juice or eat grapefruit frequently, consult with your doctor to discuss potential interactions. 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.
Overdose Information
Overdose Symptoms:
- Severe hypotension (low blood pressure)
- Bradycardia (slow heart rate)
What to Do:
There is no specific antidote. Treatment should be symptomatic and supportive. If ingestion is recent, consider gastric lavage. Monitor vital signs, kidney function, and electrolytes. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Strong UGT inhibitors (e.g., atazanavir, lopinavir/ritonavir, indinavir, saquinavir, tipranavir, nelfinavir, gemfibrozil)
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort)
Major Interactions
- Angiotensin Receptor Blockers (ARBs)
- Angiotensin-Converting Enzyme (ACE) Inhibitors
- Moderate UGT inhibitors
- Moderate CYP3A4 inducers
Moderate Interactions
- P-glycoprotein (P-gp) inhibitors
- Organic Anion Transporting Polypeptide (OATP) 1B1/1B3 inhibitors
- Potassium-sparing diuretics
- Potassium supplements
- NSAIDs (including COX-2 inhibitors)
Monitoring
Baseline Monitoring
Serum creatinine and eGFR
Rationale: To assess baseline renal function and guide dosing, and to monitor for potential renal impairment.
Timing: Prior to initiation of treatment.
Serum potassium
Rationale: To assess baseline potassium levels and monitor for hyperkalemia.
Timing: Prior to initiation of treatment.
Liver function tests (ALT, AST, total bilirubin)
Rationale: To assess baseline hepatic function and monitor for hepatotoxicity.
Timing: Prior to initiation of treatment.
Pregnancy test
Rationale: Sparsentan is contraindicated in pregnancy due to embryo-fetal toxicity. Required for females of reproductive potential.
Timing: Prior to initiation of treatment.
Routine Monitoring
Serum creatinine and eGFR
Frequency: At 2 weeks, 1 month, and then quarterly thereafter.
Target: Maintain stable renal function; monitor for significant decline.
Action Threshold: Consider dose interruption or discontinuation if clinically significant decline in eGFR or acute kidney injury occurs.
Serum potassium
Frequency: At 2 weeks, 1 month, and then quarterly thereafter.
Target: Within normal limits (e.g., 3.5-5.0 mEq/L).
Action Threshold: Consider dose interruption or discontinuation if hyperkalemia (e.g., >5.5 mEq/L) occurs.
Liver function tests (ALT, AST, total bilirubin)
Frequency: Monthly for the first 12 months of treatment, and then quarterly thereafter.
Target: Within normal limits (e.g., ALT/AST <2x ULN, total bilirubin <ULN).
Action Threshold: Discontinue if ALT/AST >3x ULN with bilirubin >2x ULN, or if ALT/AST >8x ULN. Consider interruption/discontinuation if ALT/AST >3x ULN.
Pregnancy test
Frequency: Monthly for females of reproductive potential.
Target: Negative.
Action Threshold: Discontinue 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, syncope)
- Signs and symptoms of worsening renal function (e.g., decreased urine output, swelling in legs/feet)
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Sparsentan can cause major birth defects and fetal death. Females of reproductive potential must use effective contraception prior to treatment, during treatment, and for 1 month after the last dose. A negative pregnancy test is required before starting treatment and monthly thereafter.
Trimester-Specific Risks:
First Trimester:
High risk of embryo-fetal toxicity, including major birth defects.
Second Trimester:
High risk of embryo-fetal toxicity, including major birth defects and fetal death.
Third Trimester:
High risk of embryo-fetal toxicity, including major birth defects and fetal death.
Lactation
Contraindicated during lactation. It is unknown if sparsentan is excreted in human milk, but due to the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment and for 1 month after the last dose.
Infant Risk:
High risk of serious adverse reactions.
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 (65 years and older) and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. Dose adjustment is not routinely required based on age, but consider the greater likelihood of decreased renal function in older patients.
Clinical Information
Clinical Pearls
- Filspari is the first non-immunosuppressive treatment specifically approved for IgA nephropathy (IgAN) to reduce proteinuria.
- Due to the risks of embryo-fetal toxicity and hepatotoxicity, Filspari is only available through a restricted program called the FILSPARI REMS program.
- Strict adherence to the REMS program requirements, including regular pregnancy testing and liver function monitoring, is critical.
- Patients should be educated on the importance of contraception and reporting any signs of liver injury or hyperkalemia immediately.
- Avoid concomitant use with ACE inhibitors or ARBs due to increased risk of hyperkalemia, hypotension, and acute kidney injury.
- Take on an empty stomach for optimal absorption.
Alternative Therapies
- SGLT2 inhibitors (e.g., dapagliflozin, canagliflozin) for proteinuria reduction in CKD, including IgAN.
- Angiotensin-Converting Enzyme (ACE) Inhibitors or Angiotensin Receptor Blockers (ARBs) - standard of care for proteinuria, but not to be used concurrently with sparsentan.
- Corticosteroids (e.g., prednisone) - used for immunosuppression in IgAN.
- Immunosuppressants (e.g., cyclophosphamide, mycophenolate mofetil, rituximab) - used in more severe or progressive IgAN.
- Supportive care (e.g., blood pressure control, dietary modifications).
Cost & Coverage
Average Cost:
Highly variable, typically >$10,000 per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy, and/or quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with 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. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred. This information will help healthcare professionals provide you with the most effective treatment.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with 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. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred. This information will help healthcare professionals provide you with the most effective treatment.