Version July 2025
Serious thrombotic events have occurred in fitusiran-treated patients with risk factors for thromboembolism including persistent antithrombin (AT) activity less than 15%, use of fitusiran 80 mg once monthly, presence of indwelling venous catheters, and in the post-operative setting when bleed management guidelines were not followed. Monitor AT activity using an FDA-cleared test and target AT activity 15% to 35% to reduce the risk of thrombosis. Monitor patients for signs and symptoms of thrombotic events. Interrupt fitusiran in patients with a thrombotic event and manage as clinically indicated.
Acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis have occurred in fitusiran-treated patients, some of whom required cholecystectomy or had complications (eg, pancreatitis) related to gallbladder disease. Monitor patients for signs and symptoms of acute and recurrent gallbladder disease. Consider interruption or discontinuation of fitusiran if gallbladder disease occurs. Consider alternative treatment for hemophilia in patients with a history of symptomatic gallbladder disease.
Hemophilia A, prophylaxis: Note: Measure antithrombin (AT) activity prior to initiation; do not initiate if AT activity is <60%. After fitusiran is initiated, patients may continue their prior clotting factor concentrate (CFC) or bypassing agent (BPA) prophylaxis for the first 7 days of treatment. Discontinue CFC or BPA prophylaxis no later than 7 days after the initial dose of fitusiran.
Initial:
Children ≥12 years and Adolescents: SUBQ: 50 mg every 2 months; measure AT activity after 1 month and adjust maintenance dosage based on result.
Maintenance dosage:
Children ≥12 years and Adolescents: SUBQ: Adjust dosage as per table below to maintain AT activity of 15% to 35%.
If AT activity <15%: Reduce dose as per table; initiate new dose 3 months after the previous dose.
If AT activity >35% after 6 months, or patient has not achieved satisfactory bleed control: Consider dose escalation.
|
Last fitusiran dose administered |
AT activity level |
Dose adjustment (SUBQ)b |
|---|---|---|
|
a AT = antithrombin. | ||
|
b Measure AT activity level at months 1, 3, 5, and 6 after initiation and after dosage modification. Once the patient's target dose is identified to achieve AT activity 15% to 35%, measure AT activity annually. | ||
|
c Initiate new dose 3 months after the previous dose. | ||
|
50 mg every 2 months |
<15% |
Reduce dose to 20 mg every 2 monthsc |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 50 mg every month | |
|
20 mg every 2 months |
<15% |
Reduce dose to 10 mg every 2 monthsc |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 20 mg every month | |
|
10 mg every 2 months |
<15% |
Discontinue fitusiran |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 10 mg every month | |
Hemophilia B, prophylaxis: Note: Measure antithrombin (AT) activity prior to initiation; do not initiate if AT activity is <60%. After fitusiran is initiated, patients may continue their prior clotting factor concentrate (CFC) or bypassing agent (BPA) prophylaxis for the first 7 days of treatment. Discontinue CFC or BPA prophylaxis no later than 7 days after the initial dose of fitusiran.
Initial:
Children ≥12 years and Adolescents: SUBQ: 50 mg every 2 months; measure AT activity after 1 month and adjust maintenance dosage based on result.
Maintenance dosage:
Children ≥12 years and Adolescents: SUBQ: Adjust dosage as per table below to maintain AT activity between 15% and 35%.
If AT activity <15%: Reduce dose as per table; initiate new dose 3 months after the previous dose.
If AT activity >35% after 6 months, or patient has not achieved satisfactory bleed control: Consider dose escalation.
|
Last fitusiran dose administered |
AT activity level |
Dose adjustment (SUBQ)b |
|---|---|---|
|
a AT = antithrombin. | ||
|
b Measure AT activity level at months 1, 3, 5, and 6 after initiation and after dosage modification. Once the patient's target dose is identified to achieve AT activity 15% to 35%, measure AT activity annually. | ||
|
c Initiate new dose 3 months after the previous dose. | ||
|
50 mg every 2 months |
<15% |
Reduce dose to 20 mg every 2 monthsc |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 50 mg every month | |
|
20 mg every 2 months |
<15% |
Reduce dose to 10 mg every 2 monthsc |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 20 mg every month | |
|
10 mg every 2 months |
<15% |
Discontinue fitusiran |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
Increase dose to 10 mg every month | |
Breakthrough bleeding management:
Hemophilia A or B: Children ≥12 years and Adolescents: Breakthrough bleeding requiring on-demand treatment with clotting factor concentrate (CFC) or bypassing agents (BPA):
Occurring ≤7 days after fitusiran initiation: Manage bleed using patient's prior established dosing regimen of CFC or BPA.
Occurring >7 days after fitusiran initiation: Use reduced dose and frequency of CFC/BPA to minimize risk of thrombotic events.
Dosage adjustment for concomitant therapy : Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Management of perioperative patients: Hemophilia A or B: Utilize bleed management guidelines during perioperative period; patients in clinical trials underwent minor and major surgery without discontinuing fitusiran.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Impairment prior to treatment initiation:
Children ≥12 years and Adolescents: Avoid use in any degree of hepatic impairment.
Hepatotoxicity during treatment:
New or worsening abnormalities in AST or ALT (<5 × ULN) or total bilirubin <2.5 mg/dL: Initiate medical management as appropriate; monitor laboratory parameters until they return to baseline.
ALT or AST >5 × ULN or total bilirubin ≥2.5 mg/dL: Interrupt therapy until ALT and/or AST return to baseline; consider risks and benefits for restarting. If therapy is restarted and ALT or AST elevations >5 × ULN reoccur or the patient experiences jaundice (total bilirubin ≥2.5 mg/dL) thought to be from hepatotoxicity with other causes of liver test elevation ruled out, permanently discontinue.
(For additional information see "Fitusiran: Drug information")
Hemophilia A or B, prophylaxis: Note: Indicated for patients with hemophilia A or B with or without factor VIII inhibitors. Measure antithrombin (AT) activity prior to initiation; do not initiate if AT activity is <60%. After fitusiran is initiated, patients may continue their prior clotting factor concentrate (CFC) or bypassing agent (BPA) prophylaxis for the first 7 days of treatment. Discontinue CFC or BPA prophylaxis no later than 7 days after the initial dose of fitusiran.
Initial dose: SUBQ: 50 mg once every 2 months.
Maintenance dosage:
Maintenance dosage adjustment: Measure plasma AT activity at weeks 4, 12, 20, and 24 following initial dose and after any dose modification. Adjust dose and/or interval to maintain AT activity between 15% to 35%. If AT activity <15%, reduce dose. The new, lower dose should be initiated 3 months after the prior dose. If AT activity >35% after 6 months or if satisfactory bleed control has not been achieved, dose escalation should be considered. AT measurements should be restarted after dose modification. Adjust dose based on the table below. Once the patient's target dose is identified based on AT activity 15% to 35%, measure AT activity annually.
|
Last fitusiran SUBQ dose administered |
Antithrombin activity level |
Dose adjustment (SUBQ) |
|---|---|---|
|
50 mg every 2 months |
<15% |
20 mg every 2 months |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
50 mg every month | |
|
20 mg every 2 months |
<15% |
10 mg every 2 months |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
20 mg every month | |
|
10 mg every 2 months |
<15% |
Discontinue fitusiran |
|
15% to 35% |
Continue current dose | |
|
>35% after 6 months |
10 mg every month |
Breakthrough bleeding and/or perioperative management:
For breakthrough bleeding, treatment with CFC or BPA can be used. Reduced doses are recommended for patients on fitusiran; see table below and/or individual factor product monographs. Consultation with a hemophilia provider or transfer of care to a hemophilia treatment center is recommended. General recommendations include:
During first 7 days of fitusiran initiation: Manage bleed using the patient's prior dosing regimen of CFC or BPA.
After 7 days of first fitusiran dose: Manage bleed with a reduced dose and frequency of CFC/BPA to minimize the risk of thrombotic events. Initially, the weight-based dose of a CFC/BPA should be reduced, and the dosing interval doubled compared to the standard dose. If adequate hemostatic control is not achieved, higher doses or more frequent administration may be considered based on clinical judgment. For situations requiring higher doses, more frequent administration, or multiple repeated doses, antithrombin replacement may be considered (Ref).
|
Factor VIII |
Standard half-life factor IX |
Extended half-life factor IX |
Activated prothrombin complex concentrate |
Activated recombinant factor VII | |
|
Recommended dose |
10 to 20 units/kg |
20 to 30 units/kg |
20 to 30 units/kg |
30 to 50 units/kg |
≤45 mcg/kg |
|
Repeat dosing |
Should not repeat in <24 hours |
Should not repeat in <24 hours |
Should not repeat in <5 to 7 days |
Should not repeat in <24 hours |
Should not repeat in <2 hours |
Missed dose: If a dose is missed, administer as soon as possible; and then resume the usual dosing schedule from the last dose.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Liver impairment prior to treatment initiation:
Child-Turcotte-Pugh class A, B, or C: Avoid use.
Hepatotoxicity during treatment:
ALT or AST elevations >5 × ULN: Interrupt therapy until transaminase elevations return to baseline. If therapy is restarted and ALT or AST elevations >5 × ULN reoccur, or the patient experiences jaundice (total bilirubin ≥2.5 mg/dL) thought to be from hepatotoxicity with other causes of liver test elevation ruled out, permanently discontinue.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.
>10%:
Infection: Bacterial infection (11%), viral infection (29%)
Respiratory: Nasopharyngitis (26%)
1% to 10%:
Cardiovascular: Thrombosis (1%)
Gastrointestinal: Abdominal pain (<5%), dyspepsia (<5%), gallbladder disease (4%; including cholecystectomy [<1%], cholecystitis, cholelithiasis)
Hematologic & oncologic: Blood coagulation test abnormality (prothrombin fragment 1.2 increased: 7%)
Hepatic: Hepatic injury (8%; including increased serum alanine aminotransferase [3%], increased serum aspartate aminotransferase)
Immunologic: Antibody development (3%)
Local: Injection-site reaction (6%)
Nervous system: Headache (5%)
Neuromuscular & skeletal: Arthralgia (8%)
Respiratory: Cough (5%)
Frequency not defined:
Cardiovascular: Deep vein thrombosis (postoperative)
Dermatologic: Pruritus
Nervous system: Cerebral infarction
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Gallbladder disease: Treatment has been associated with increased rates of acute and recurrent cholelithiasis and cholecystitis. Fixed-dose regimens (ie, not based on antithrombin monitoring) increase the risk of occurrence. Consider alternative treatment for hemophilia in patients with a history of symptomatic gallbladder disease. Consider interruption or discontinuation if gallbladder disease occurs.
• Hepatotoxicity: Serum transaminase elevations have been observed. Doses ≥80 mg should not be utilized.
• Thromboembolic events: Serious thrombotic events have been reported. Risk factors include persistent antithrombin activity <15%, comorbidities that predispose to thrombosis (eg, arterial or venous thromboembolism, significant valvular disease, atrial fibrillation, coexisting thrombophilic disorder), failure to follow bleeding management guidelines perioperatively, indwelling venous catheter, and the use of a dose greater or more frequent than recommended (eg, 80 mg).
Disease-related concerns:
• Liver impairment: Avoid use in patients with liver impairment (Child-Turcotte-Pugh class A, B, and C).
Concurrent drug therapy issues:
• Medications for bleeding management: When used concomitantly with clotting factor concentrates (CFCs) or bypassing agents (BPAs), an additive increase in peak thrombin generation is seen. CFC or BPA prophylaxis may be continued for the first 7 days of treatment. Discontinue CFC/BPA no longer than 7 days following initial dose. Treatment of breakthrough bleeding episodes with CFC or BPA at a dose greater or more frequent than recommended may increase thrombotic risk.
Special populations:
• Management of perioperative patients: Consultation with a hemophilia provider is recommended to determine the need for supplemental CFC administration and/or antithrombin concentrate.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous, as sodium [preservative free]:
Qfitlia: 20 mg/0.2 mL (0.2 mL)
Solution Auto-injector, Subcutaneous, as sodium [preservative free]:
Qfitlia: 50 mg/0.5 mL (0.5 mL)
No
Solution (Qfitlia Subcutaneous)
20 mg/0.2 mL (per 0.2 mL): $77,472.00
Solution Auto-injector (Qfitlia Subcutaneous)
50 mg/0.5 mL (per 0.5 mL): $193,680.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Note: Caregivers may administer, or properly trained patients may self-administer under adult supervision.
Parenteral: SUBQ: If stored in the refrigerator, remove and allow to reach room temperature for ≥30 minutes before use. Administer SUBQ in the thigh or abdomen (at least 5 cm [2 inches] away from navel). May also be administered SUBQ by a caregiver in the outer area of the patient's upper arm. Do not inject in areas where the skin is tender, damaged, bruised, or scarred, or where there are visible veins. Solution is clear and colorless to pale yellow; do not use if discolored or cloudy, or if visible flakes or particles are present; do not use if product has been dropped or damaged. Do not shake, heat, freeze, or expose to direct sunlight.
Prefilled pen: Do not use if blue cap is missing or not securely attached, or if the window is yellow before use. After removing blue cap, place orange needle cover at a 90-degree angle on skin at injection site. Press down and hold firmly until orange needle cover cannot be seen; a click will be audible when injection starts; hold until window turns completely yellow; a second click may be heard. Pull pen straight up and do not rub the skin after the injection. After use, discard any unused product remaining in pen. Do not reuse.
Single-dose vial: Use a sterile 1 mL polypropylene or polycarbonate Luer Lock syringe and a sterile 27-gauge 1/2-inch Luer Lock needle to withdraw solution from vial prior to SUBQ administration. Pinch a fold of skin at injection site and insert needle at a 45 to 90-degree angle; relax skin pinch and slowly inject dose. After use, discard any unused product remaining in vial.
Missed dose: Administer as soon as possible, then resume the patient's usual dosing schedule from the last dose.
SUBQ: If prefilled pens and vials are stored in the refrigerator prior to administration, remove and allow to reach room temperature for at least 30 minutes. May be self-administered or administered by a caregiver after appropriate training. Administer by SUBQ injection in the thigh or abdomen (at least 2 inches from navel); may be administered into upper arm by caregiver only. Do not inject into vein or in a site that is tender, damaged, bruised, or scarred; do not rub injection site after administration. Do not use if discolored, cloudy, or contains visible flakes or particles. Discard any unused product remaining in the prefilled pen or vial.
Prefilled pens: Store at 2°C to 8°C (36°F to 46°F) in original carton to protect from light; do not freeze, heat, or shake. May be stored between 15°C to 30°C (59°F to 86°F) for up to 3 months. Once stored at room temperature, do not return to refrigerator; discard after 3 months.
Vials: Store at 2°C to 8°C (36°F to 46°F) or between 15°C to 30°C (59°F to 86°F) in original carton to protect from light; do not freeze, heat, or shake. Once stored at room temperature, do not return to refrigerator.
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency) who do or do not have factor VIII inhibitors, or hemophilia B (congenital factor IX deficiency) who do or do not have factor IX inhibitors (FDA approved in ages ≥12 years and adults).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Clotting Factor Concentrates (CFCs) and Bypassing Agents (BPAs): Fitusiran may increase thrombogenic effects of Clotting Factor Concentrates (CFCs) and Bypassing Agents (BPAs). Management: Stop CFC/BPA prophylaxis no later than 7 days after starting fitusiran. If bleeding occurs during the first 7 days of fitusiran, manage with the prior dosing regimen of CFC/BPA. If bleeding occurs after 7 days, use reduced CFC/BPA doses and frequencies. Risk D: Consider Therapy Modification
Hormonal contraceptives may increase the risk of thrombotic events in patients with inherited antithrombin deficiency. Nonhormonal contraception is recommended prior to and during treatment with fitusiran.
Animal reproduction studies have not been conducted.
Antithrombin (AT) activity at baseline and at months 1, 3, 5, and 6 following starting dose or any dose modification, annually once target dose is identified, and for 6 months following discontinuation if treatment with clotting factor concentrations or bypassing agents is required for bleeding. AST, ALT, and total bilirubin at baseline, monthly for at least the first 6 months after initiation or a dose increase, then periodically as clinically appropriate. Signs and symptoms of thrombotic events or gallbladder disease (eg, epigastric or generalized abdominal pain, indigestion, nausea/vomiting).
Target antithrombin activity: 15% to 35%
Fitusiran is a double-stranded small interfering ribonucleic acid that causes degradation of antithrombin (AT) messenger RNA through RNA interference, reducing plasma AT levels.
Duration: Most patients have antithrombin activity >60% by 6 months after the last dose.
Protein binding: 96.6%.
Metabolism: Metabolized by endo- and exonucleases to oligonucleotides.
Half-life elimination: 20 mg dose: 5.57 ± 2.36 hours; 50 mg dose: 7.98 ± 4.74 hours; steady state reached within 23 weeks.
Time to peak: 0.5 to 4.33 hours (20 mg); 0.42 to 11.9 hours (50 mg).
Excretion: Urine (50 mg dose: 14.6% as unchanged drug).
Sex: Studies of fitusiran have only been performed in male patients.
