Fitusiran Dosage

Usual Adult Dose for Hemophilia A

Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Adult Dose for Hemophilia B

Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Adult Dose for Hemophilia A with Inhibitors

Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Adult Dose for Hemophilia B with Inhibitors

Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Pediatric Dose for Hemophilia A

12 YEARS AND OLDER:
Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Pediatric Dose for Hemophilia B

12 YEARS AND OLDER:
Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Pediatric Dose for Hemophilia A with Inhibitors

12 YEARS AND OLDER:
Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Usual Pediatric Dose for Hemophilia B with Inhibitors

12 YEARS AND OLDER:
Initial dose: 50 mg subcutaneously every 2 months
Maintenance dose: Adjust dose and/or interval to maintain antithrombin (AT) activity between 15 to 35%

Comments:

• Monitor AT activity prior to therapy and during treatment as recommended by the manufacturer; use an FDA-approved test.
• Do not initiate treatment if AT activity is less than 60%.

Use: For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B with or without factor VIII or IX inhibitors

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Liver dysfunction (Child-Pugh A, B, or C): Avoid use

For ALT/AST greater than 5 times the upper limit of normal: Interrupt therapy; consider benefit vs. risk of resuming treatment after resolution.

• For recurrence, or for jaundice (total bilirubin at least 2.5 mg/dL) secondary to hepatotoxicity: Permanently discontinue treatment.

Dose Adjustments

DOSE MODIFICATIONS BASED ON ANTITHROMBIN (AT) ACTIVITY:
General Recommendations:

• Measure AT activity using an FDA-cleared test at Weeks 4 (Month 1), 12 (Month 3), 20 (Month 5) and 24 (Month 6) following the starting dose and after any dose modification.
• For AT activity less than 15%, a dose reduction is required and should be initiated 3 months after prior dose.
• For AT activity greater than 35% after 6 months or if satisfactory bleed control is not achieved, consider dose escalation.
• Once the patient's target dose is identified based on AT activity 15-35%, measure AT activity annually. Additional measurements can be considered if bleeding control is not adequate.
• Review the recommended AT monitoring schedule and dosing table in the manufacturer product information.

Current dose 50 mg every 2 months:

• AT activity level less than 15%: Reduce to 20 mg subcutaneously every 2 months
• AT activity level 15 to 35%: Continue current dosage
• AT activity level greater than 35% after 6 months: Increase to 50 mg subcutaneously once a month

Current dose 20 mg every 2 months:

• AT activity level less than 15%: Reduce to 10 mg subcutaneously every 2 months
• AT activity level 15 to 35%: Continue current dosage
• AT activity level greater than 35% after 6 months: Increase to 20 mg subcutaneously once a month

Current dose 10 mg every 2 months:

• AT activity level less than 15%: Discontinue therapy
• AT activity level 15 to 35%: Continue current dosage
• AT activity level greater than 35% after 6 months: Increase to 10 mg subcutaneously once a month

MANAGEMENT OF BREAKTHROUGH BLEEDING:
Use of Clotting Factor Concentrates (CFC) or Bypassing Agents (BPA) During Therapy:

• Within 7 days of therapy initiation: Manage using the patient's prior dosing regimen of CFC or BPA.
• After 7 days of therapy: Consult the CFC/BPA dose modification table in the manufacturer product information.
• Initially, reduce the weight-based dose and double the dosing interval as compared to standard dosing.
• If hemostatic control is not achieved, higher dose/frequency may be used based on clinical judgement.
• Six months after therapy cessation: Standard doses of CFC or BPA may be used; however, if bleeding occurs prior, monitor AT activity level before dosing.

PERIOPERATIVE RECOMMENDATIONS:
For Major and Minor Surgical Procedures:

• Utilize bleed management guidelines during the perioperative period for hemostatic management.
• In clinical studies, patients with hemophilia A or B (with or without inhibitors) underwent major/minor surgical procedures without discontinuing therapy with this drug.

RECOMMENDED MODIFICATIONS FOR ADVERSE EVENTS:

• Gallbladder Disease: Consider interruption or discontinuation of therapy.
• Thrombotic Events: Interrupt therapy and manage as clinically indicated.

Precautions

US BOXED WARNINGS:

• THROMBOTIC EVENTS: Serious thrombotic events have occurred in patients with risk factors for thromboembolism including persistent AT activity less than 15%, use of 80 mg once monthly doses, 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 at 15 to 35% to reduce the risk of thrombosis. Monitor patients for signs and symptoms of thrombotic events. Interrupt therapy in patients with a thrombotic event and manage as clinically indicated.
• ACUTE AND RECURRENT GALLBLADDER DISEASE: Acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis have occurred during therapy; some cases required cholecystectomy or had complications (e.g., pancreatitis) related to gallbladder disease. Monitor patients for signs/symptoms of acute and recurrent gallbladder disease. Consider interruption or discontinuation of treatment if gallbladder disease occurs. Consider alternative therapy for hemophilia in patients with a history of symptomatic gallbladder disease.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Consult the manufacturer product information for detailed recommendations on drug administration and monitoring.
• Prior to starting therapy, measure AT activity; do not initiate treatment if AT activity is less than 60%.
• Prophylaxis with CFC or BPA may be continued during the first 7 days of treatment, but should be discontinued 7 days after the initial dose of this drug.
• Administer subcutaneously into the thigh or abdomen, or upper arm (if given by a caregiver); avoid injection into a vein or tender, damaged, bruised, or scarred skin, or within 2 inches (5 cm) of the navel.
• If administered by a patient/caregiver, ensure proper training prior to first use; pediatric patients should be supervised during self-injection or have an adult administer injection.
• If a dose is missed, administer as soon as possible and resume the usual dosing schedule from the last dose (e.g., once a month, or every 2 months).

Storage requirements:

• Prefilled Pen: Store refrigerated at 2C to 8C (36F to 46F) in the original carton to protect from light.
• May store at room temperature between 15C to 30C (59F to 86F) for a single period of up to 3 months.
• Discard after labeled expiration date or after 3 months at room temperature, whichever comes first.
• Vial: Store refrigerated or at room temperature in the original carton to protect from light.
• After storing pens or vials at room temperature, do not return to the refrigerator.
• Do not heat, freeze, or place in direct sunlight.

Reconstitution/preparation techniques:

• Refer to the manufacturer product information for illustrated instructions on preparation/administration.
• Bring refrigerated product to room temperature for at least 30 minutes before use; do not shake.
• Inspect product for discoloration or flakes/particles; do not use if discolored/cloudy, dropped, or damaged.

General:

• Treatment should be supervised by a health care provider experienced in the treatment of hemophilia or bleeding disorders.
• Information on FDA-cleared tests for AT activity is available at: http://www.fda.gov/CompanionDiagnostics.
• The combined use of antifibrinolytics with CFC or BPA has not been studied.

Monitoring:

• Cardiovascular: For signs/symptoms of thrombotic events (during therapy)
• Hematologic: Assess AT activity level:
• After the first dose or after any dose modification at week 4, week 12, week 20, and week 24
• Annually once target dose is determined
• As indicated if bleeding control is not adequate
• As indicated within 6 months of treatment cessation if CFC/BPA is required for bleeding management
• Hepatic: ALT, AST and total bilirubin (prior to therapy, monthly for at least the first 6 months, monthly for at least 6 months after dose increases, and then periodically as indicated)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Discuss use of CFC or BPA during therapy with your health care provider prior to administration.
• Recognize the signs/symptoms of thrombotic events, gallbladder disease, and hepatotoxicity; seek medical attention if they occur.
• Understand proper preparation and administration of this drug before first use.
• Speak to a healthcare provider if you are pregnant, intend to become pregnant, or are breastfeeding.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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