Fitusiran

Fitusiran is a prescription medication indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors.  

• Fitusiran is available under the following different brand names: Qfitlia.

Common side effects of Fitusiran include:

• viral infection
• nasopharyngitis 
• bacterial infection

Serious side effects of Fitusiran include:

• abnormal blood clotting symptoms include swelling, pain or redness in arms or legs, coughing up blood, shortness of breath, severe chest pain or tightness of the chest, fast heart rate, fainting, severe or persistent headache, difficulty speaking or understanding language, feeling confused, numbness or weakness in the face, arms or legs, sudden loss or changes in the vision, eye pain or swelling
• gallbladder disease symptoms include abdominal pain, indigestion, nausea, or vomiting
• lncrease in blood liver enzymes

Rare side effects of Fitusiran 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, coordination loss, 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 and pediatric dosage
Solution for SC injection

• 20 mg/0.2 mL vial
• 50 mg/0.5 mL prefilled pen

Hemophilia A or B
Adult and pediatric dosage

• Starting dose: 50 mg SC every 2 months; adjust dose and/or interval if needed to maintain antithrombin (AT) activity between 15-35%
• Breakthrough bleeding management with clotting factor concentrates (CFC) or bypassing agent (BPA)
  • 7 days or less after initiating: Use the patient’s prior dosing regimen of CFC or BPA prophylaxis
  • More than 7 days after initiating: Manage with reduced dose and frequency of CFC/BPA to minimize thrombotic events
• CFC/BPA recommendations while treated with fitusiran
  • Initially, reduce the weight-based dose of CFC/BPA and double the dose interval
  • Use clinical judgement for situations requiring higher doses, more frequent administration, or multiple repeat doses
  • Factor VIII
    • Recommended dose: 10 units/kg; not to exceed 20 units/kg
    • Repeat dosing: Do not repeat within 24 hours
  • Factor IX (standard half-life)
    • Recommended dose: 20 units/kg; not to exceed 30 units/kg
    • Repeat dosing: Do not repeat within 24 hours
  • Factor IX (extended half-life)
    • Recommended dose: 20 units/kg; not to exceed 30 units/kg
    • Repeat dosing: Do not repeat within 5-7 days
  • Activated prothrombin complex concentrate (aPCC)
    • Recommended dose: 30 units/kg; not to exceed 50 units/kg
    • Repeat dosing: Do not repeat within 24 hours
  • Activated recombinant FVII (rFVIIa)
    • Recommended dose: 45 mcg/kg and less
    • Repeat dosing: Do not repeat within 2 hours

Dosage Considerations – Should be Given as Follows: 
See “Dosages”

If your doctor has directed you to use this medication, 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.

Drug interaction overview

• CFC or BPA
  • Avoid
  • Fitusiran prophylaxis leads to increased thrombin generation with an additive increase in peak thrombin if used concomitantly with CFC (CFC; Factor VII or Factor IX) or BPA (BPA; rFVIIa or aPPC)
  • Avoid coadministration by day 7 after initiating fitusiran
  • If breakthrough bleeding occurs, it may be temporarily treated with CFC/BPA at a reduced dose and frequency

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Serious thrombotic events reported
• Increased occurrence of acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis

Hepatotoxicity

• Increased ALT and AST were reported during clinical trials, especially with doses higher than recommended
• Avoid use with any degree of hepatic impairment (Child-Pugh class A, B, and C)
• Obtain baseline liver tests, including AST, ALT, and total bilirubin (TB), before initiating, monthly for at least 6 months, and monthly for at least 6 months after a dose increase, and periodically thereafter as clinically indicated
• If new or worsening liver test abnormalities occur, perform appropriate diagnostic evaluations, initiate medical management, and monitor laboratory parameters until they return to baseline
• Interrupt treatment if ALT or AST elevations of 5x ULN and more occur
• Consider the benefits and risks of resuming prophylaxis following resolution
• If dosing is restarted, wait until liver tests have returned to baseline
• Permanently discontinue if dosing restarted and ALT/AST elevations of 5x ULN and more recur, or the patient develops jaundice (TB more than 2.5 mg/dL) thought to be from hepatotoxicity, with other causes of liver test elevation ruled out

Pregnancy and Lactation

• Data are unavailable in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Reproduction studies in pregnant animals have not been conducted

Contraception

• Use in women receiving hormonal contraceptives may increase the risk of thrombotic events
• Estrogen-based hormonal contraceptives are an established risk factor for thrombosis in women with inherited AT deficiency
• Advise patients using hormonal contraceptives to use an alternate nonhormonal contraception before starting treatment and while receiving fitusiran

Lactation

• Data are unavailable regarding the presence of fitusiran or its metabolite in human milk, its effects on breastfed children, or milk production