QFITLIA Solution for injection Ref.[115543] Active ingredients: Fitusiran

2.1 Recommended Dosage

For subcutaneous use only.

Use of QFITLIA is recommended under the supervision of a healthcare professional experienced in the treatment of hemophilia or bleeding disorders.

Monitor AT activity using an FDA-cleared test. Information on FDA-cleared tests for AT activity is available at http://www.fda.gov/CompanionDiagnostics.

Measure AT activity prior to initiation of QFITLIA. Do not initiate QFITLIA dosing if AT activity is <60%.

After QFITLIA is initiated, patients may continue their prior clotting factor concentrates (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 QFITLIA.

The starting dose of QFITLIA is 50 mg once subcutaneously every two months. Adjust the dose and/or dosing interval, if needed, to maintain AT activity between 15–35% [see Boxed Warning, Dosage and Administration (2.2) and Warnings and Precautions (5.1)].

2.2 Dosage Modification

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.

• If any AT activity is <15%, a dose reduction is required. The lower dose should be initiated 3 months after the prior dose. AT measurements should be restarted after a dose reduction.
• If AT activity is >35% after 6 months, or if the patient has not achieved satisfactory bleed control, dose escalation should be considered. AT measurements should be restarted after a dose escalation.

Refer to Table 1 below for modified dosage based on AT activity levels.

Table 1. Dose Modification Based on Antithrombin Activity Levels:

Once the patient's target dose is identified based on AT activity 15–35%, measure AT activity annually. Additional AT measurements can be considered if bleeding control is not adequate.

After cessation of QFITLIA dosing, routine AT monitoring is not needed unless the patient is bleeding and treatment with CFC/BPA is required. Based on data from the clinical studies, a majority of patients have AT activity >60% by 6 months after the last QFITLIA dose, after which standard doses of CFC/BPA may be used.

Missed dose

If a dose of QFITLIA is missed, administer as soon as possible; thereafter, resume the patient's usual dosing schedule of either once every month or once every two months, as applicable, from the last dose.

2.3 Bleed Management

Breakthrough Bleed Management

If breakthrough bleeding requiring on-demand treatment with CFC or BPA occurs during the first 7 days after QFITLIA initiation, manage the bleed using the patient's prior dosing regimen of CFC or BPA.

If breakthrough bleeding occurs after 7 days from the first QFITLIA dose, bleeds should be managed 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. This reduced dosing is shown in Table 2. If adequate hemostatic control is not achieved, higher doses may be used based on clinical judgement. Combination use of antifibrinolytics with CFC or BPA has not been studied.

Table 2. Breakthrough Bleed Management While Treated with QFITLIA:

aPCC = activated prothrombin complex concentrate, EHL = extended half-life, rFVIIa = activated recombinant FVII, SHL = standard half-life.

Use of QFITLIA During Surgical Interventions

In clinical studies, patients with hemophilia A or B with or without inhibitors have undergone both major (N=60) and minor (N=71) surgical procedures without discontinuing QFITLIA prophylaxis. Utilize bleed management guidelines during the perioperative period for hemostatic management.

2.4 Preparation and Administration Instructions

QFITLIA is intended for use under the guidance of a healthcare provider. Provide proper training to patients and/or caregivers on the preparation and administration of QFITLIA prior to use, according to the Instructions for Use (IFU). A patient may self-inject QFITLIA or the patient's caregiver may administer QFITLIA. In pediatric patients 12 to 17 years of age, it is recommended that QFITLIA be administered by or under the supervision of an adult.

QFITLIA for subcutaneous administration is a clear, colorless to pale yellow solution. Do not use if the solution is discolored or cloudy, or if it contains visible flakes or particles. Do not use QFITLIA if it has been dropped or damaged.

If QFITLIA is stored at room temperature, it is ready for use. If QFITLIA is stored in the refrigerator, remove from the refrigerator and allow QFITLIA to reach room temperature, for at least 30 minutes.

Administer QFITLIA by subcutaneous injection in the thigh or abdomen region, except for the 2 inches (5 cm) around the navel. A caregiver can also inject QFITLIA in the outer area of the patient's upper arm. QFITLIA should not be injected into skin that is tender, damaged, bruised, or scarred. Do not inject into a vein.

To inject 10 mg or 20 mg of QFITLIA from the single-dose vial, it is recommended to use a sterile 1 mL Luer Lock syringe (polypropylene or polycarbonate), and a sterile 27 gauge ½ inch (13 mm) Luer Lock needle to withdraw and inject QFITLIA solution subcutaneously (see the Instructions for Use).

Discard unused product remaining in the prefilled pen or vial.

50 mg Prefilled Pen:

• Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
• QFITLIA may be stored at room temperature between 15°C to 30°C (59°F to 86°F) for a single period of up to 3 months within the expiration date printed on the label. Discard no later than 3 months after removal from the refrigerator or at the expiration date, whichever comes first. After storage at room temperature, do not return the product to the refrigerator.

20 mg Vial:

• Store QFITLIA either in the refrigerator at 2°C to 8°C (36°F to 46°F) or at room temperature between 15°C to 30°C (59°F to 86°F), in the original carton to protect from light. After storage at room temperature, do not return the product to the refrigerator.

Do not shake QFITLIA at any time. Do not heat QFITLIA. Do not freeze. Do not put into direct sunlight.