Filspari is a prescription medicine used to reduce levels of protein in the urine (proteinuria) in adults with a kidney disease called primary immunoglobulin A nephropathy (IgAN).

Filspari is a Dual Endothelin Angiotensin Receptor Antagonist (DEARA) that works by targeting two pathways (endothelin-1 and angiotensin II) that are involved in the progression of IgAN.

What is Filspari used to treat?

Filspari is used to treat IgA nephropathy (IgAN), the most common type of primary glomerulonephritis and a leading cause of kidney failure due to glomerular disease. It is used in people at risk of rapid disease progression.

IgA nephropathy is a rare, progressive kidney disease characterized by the buildup of the protein immunoglobulin A (IgA) in the kidneys. The depostis of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to hematuria (blood in the urine), proteinuria (protein in the urine), and a progressive loss of kidney function. Other symptoms of IgAN may include edema (swelling) and hypertension (high blood pressure).

Filspari is approved to reduce proteinuria in adults with primary IgAN who are at risk of rapid disease progression. This indication was granted under accelerated approval based on reduction in proteinuria. It has not been established whether Filspari slows kidney function decline in patients with IgAN. Continued approval may be contingent upon confirmation of clinical benefit in an ongoing clinical study.

It is not known if this medicine is safe and effective in children.

Filspari is only available through the Filspari REMS Program.
Before you start treatment, you must read and agree to all of the instructions in the Filspari REMS Program.

Filspari can cause serious side effects, including:

Liver problems.

• Filspari can cause changes in liver tests. Some medicines that are like Filspari can cause liver failure. Your healthcare provider will do blood tests to check your liver before starting treatment, monthly for the first 12 months, and then every 3 months. Your healthcare provider may temporarily stop or permanently stop treatment if you have changes in your liver tests.
  
  Tell your healthcare provider right away if you develop any of the following signs of liver problems during treatment:
  • nausea or vomiting
  • pain on the upper right side of your stomach area
  • 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.

Filspari can cause serious birth defects if taken during pregnancy.

• Patients who can become pregnant must not be pregnant when they start taking Filspari or become pregnant during treatment with Filspari or for 1 month after stopping treatment.
• Patients who can become pregnant must have a negative pregnancy test before starting treatment and must have a monthly negative pregnancy test during treatment and 1 month after stopping treatment.
  • Patients who can become pregnant are those who:
    • have entered puberty, even if they have not started their menstrual period, and
    • have a uterus, and
    • have not gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed.
  • Patients who cannot become pregnant are those who:
    • have not yet entered puberty, or
    • do not have a uterus, or
    • have gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed, or
    • are infertile for any other medical reason and this infertility is permanent and cannot be reversed.

Patients who can become pregnant must use effective birth control during treatment with Filspari and for 1 month after stopping Filspari because the medicine may still be in your body.

• If you have had a tubal sterilization or have an IUD (intrauterine device) or progesterone implant, these methods may be used alone, and no other form of birth control is needed.
• Talk with your healthcare provider or gynecologist (a healthcare provider who specializes in reproduction) to find out about options for effective forms of birth control that you may use to prevent pregnancy during treatment.
• If you decide that you want to change the form of birth control that you use, talk with your healthcare provider or gynecologist to be sure that you choose another effective form of birth control.

See the chart below for acceptable birth control options during treatment with Filspari.

• Do not have unprotected sex. Talk to your healthcare provider or pharmacist right away if you have unprotected sex or if you think your birth control has failed. Your healthcare provider may talk with you about using emergency birth control.
• Tell your healthcare provider right away if you miss a menstrual period or think you may be pregnant.

• Filspari tablets will be provided to you by a certified pharmacy. Your healthcare provider will give you complete details.
• Take this medicine exactly as your healthcare provider tells you to take it. Do not stop treatment unless your healthcare provider tells you.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment if you develop side effects.
• Swallow the tablets whole with water before your morning or evening meal. Take your dose with the same meal each day.
• If you miss a dose, take the next dose at the regularly scheduled time. Do not take 2 doses at the same time or take extra doses.
• Talk to your healthcare provider before using antacid medicines because they may affect how Filspari works. Antacids should not be taken within 2 hours before or after a dose of Filspari.
• If you take too much or overdose, call your healthcare provider or go to the nearest hospital emergency room right away.

Usual Adult Dose for IgA Nephropathy:

200 mg orally once daily for 14 days, then 400 mg once daily, as tolerated.

Comments:
- prior to initiating treatment, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors, endothelin receptor antagonists (ERAs) or aliskiren.

Use:
- to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. This indication is approved under accelerated approval based on reduction of proteinuria. It has not been established whether Filspari slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

Do not take Filspari if you:

• are pregnant, plan to become pregnant, or become pregnant during treatment. Filspari can cause serious birth defects. See Important information.
• are taking any of these medicines:
  • an angiotensin receptor blocker, or
  • an endothelin receptor antagonist, or
  • aliskiren.

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

Before taking Filspari

Before you take Filspari, tell your healthcare provider about all of your medical conditions, including if you have:

• high blood pressure or heart problems
• liver problems.

• Do not get pregnant while taking Filspari. If you miss a menstrual period, or think you might be pregnant, call your healthcare provider right away.
• It is not known if Filspari passes into your breast milk. You should not breastfeed if you are taking Filspari. Talk to your healthcare provider about the best way to feed your baby during treatment.

Filspari can cause serious side effects, including:

• Liver problems. See Important information.
• Serious birth defects. See Important information.
• Low blood pressure. Low blood pressure is common during treatment with Filspari 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. Your healthcare provider will check your kidney function during treatment.
• Increased potassium in your blood. This is common during treatment with Filspari and can also be serious.
  Your healthcare provider will check your potassium blood level during treatment.
• Fluid retention. Filspari 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.

The most common side effects include:

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

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

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements and grapefruit. Filspari and other medicines may affect each other and cause side effects.

You should not take Filspari if you are taking any of these medicines:

• an angiotensin receptor blocker, or
• an endothelin receptor antagonist (ambrisentan, bosentan, macitentan), or
• aliskiren.

Especially tell your healthcare provider if you take:

• nonsteroidal anti-inflammatory drugs (increased risk of kidney injury)
• potassium-containing medicines, potassium supplements or salt substitutes containing potassium (increased risk of hyperkalemia)
• blood pressure medicines (increased the risk of hypotension)
• antacid medicines and acid reducing medicines (may decrease the effect of Filspari).

This is not a complete list of all the medicines that may interact with Filspari. Do not start any new medicine until you check with your healthcare provider.