WINREVAIR Powder and solvent for solution for injection Ref.[114917] Active ingredients: Sotatercept

Winrevair treatment should only be initiated and monitored by a physician experienced in the diagnosis and treatment of PAH.

Posology

Winrevair is administered once every 3 weeks as a single subcutaneous injection according to patient weight.

Recommended starting dose

Haemoglobin (Hgb) and platelet count should be obtained prior to the first dose (see section 4.4). Initiation of treatment is contraindicated if platelet count is consistently <50 × 10⁹/L (see section 4.3).

Treatment is initiated with a single dose of 0.3 mg/kg (see Table 1).

Table 1. Injection volume for dose of 0.3 mg/kg:

^* The concentration of the reconstituted solution is 50 mg/mL (see section 6.6)

Recommended target dose

Three weeks after a single starting dose of 0.3 mg/kg, the dose should be escalated to the recommended target dose of 0.7 mg/kg after verifying acceptable Hgb and platelet count (see section 4.2 “Dose adjustments due to increase in haemoglobin or decreased platelet count”). Treatment should be continued at 0.7 mg/kg every 3 weeks unless dose adjustments are required.

Table 2. Injection volume for dose of 0.7 mg/kg:

^* The concentration of the reconstituted solution is 50 mg/mL (see section 6.6)

Dose adjustments due to increase in haemoglobin or decreased platelet count

Hgb and platelet count should be monitored for the first 5 doses, or longer if values are unstable. Thereafter, Hgb and platelet count should be verified every 3 to 6 months and the dose adjusted if necessary (see sections 4.4 and 4.8).

Treatment should be delayed for 3 weeks (i.e., one dose delay) if any of the following occur:

• Hgb increases >1.24 mmol/L (2 g/dL) from the previous dose and is above the ULN.
• Hgb increases >2.48 mmol/L (4 g/dL) from baseline.
• Hgb increases >1.24 mmol/L (2 g/dL) above ULN.
• Platelet count decreases <50 × 10⁹/L.

Hgb and platelet count should be obtained again before reinitiating treatment.

For treatment delays lasting >9 weeks, treatment should be restarted at 0.3 mg/kg, and the dose should be escalated to 0.7 mg/kg after verifying acceptable Hgb and platelet count.

For treatment delays lasting >9 weeks due to platelet counts consistently <50 × 10⁹/L, the physician should carry out a benefit/risk re-evaluation for the patient before reinitiating treatment.

Missed dose

If a dose is missed, administer as soon as possible. If the missed dose is not taken within 3 days of the scheduled date, adjust the schedule to maintain 3-week dosing intervals.

Elderly

No dose adjustment is required in elderly patients ≥65 years old (see section 5.2).

Renal impairment

No dose adjustment is required based on renal impairment (see section 5.2). Sotatercept has not been studied in PAH patients with severe renal impairment (estimated glomerular filtrati on rate (eGFR) <30 mL/min/1.73m²).

Hepatic impairment

No dose adjustment is required based on hepatic impairment (Child-Pugh Classification A to C). Sotatercept has not been studied in patients with hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Winrevair in children and adolescents below 18 years of age have not yet been established. No data are available (see section 5.3).

Method of administration

Winrevair is for single use only.

It should be reconstituted before use. The reconstituted medicinal product is a clear to opalescent and colourless to slightly brownish-yellow solution.

Winrevair should be administered by subcutaneous injection in the abdomen (at least 5 cm away from navel), upper arm, or upper thigh. It should not be injected into sites that are scarred, tender, or bruised. The same injection site should not be used on two consecutive injections.

Winrevair powder and solvent for solution for injection is intended for use under the guidance of a healthcare professional (HCP). Patients and caregivers may administer the medicinal product when considered appropriate and when they rece ive training from a HCP in how to reconstitute , prepare, measure and inject Winrevair powder and solvent for solution for injection. A HCP should confirm at a subsequent visit, soon after training, that the patient or caregiver can perform these steps correctly. A HCP should also consider reconfirming the patient’s or caregiver’s administration technique if the dose is adjusted, if the patient requires a different kit, if the patient develops erythrocytosis (see section 4.4), or at any time at the discretion of the HCP.

Refer to section 6.6 for detailed instructions on the proper preparation and administration of Winrevair.

In a phase 1 healthy volunteer study, one participant dosed at 1 mg/kg of sotatercept experienced increased Hgb associated with symptomatic hypertension that improved with phlebotomy.

In the event of overdose in a patient with PAH, increases in Hgb and blood pressure should be closely monitored, and supportive care should be provided as appropriate (see sections 4.2 and 4.4). Sotatercept is not dialyzable during haemodialysis.

Unopened vial:

3 years.

After reconstitution:

Biochemical and biophysical in-use stability has been demonstrated for 4 hours at 30°C.

From a microbiological point of view, the medicinal product should be used immediately or no longer than 4 hours after reconstitution.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Store in a refrigerator (2°C–8°C). Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Winrevair 45 mg powder and solvent for solution for injection:

2 mL capacity, type I glass vial sealed with a bromobutyl rubber stopper with polymer coating and aluminium seal with lime polypropylene flip-off cap containing 45 mg of sotatercept.

Prefilled syringe (type I glass cartridge closed with a bromobutyl rubber stopper) with 1 mL of solvent.

Winrevair 60 mg powder and solvent for solution for injection:

2 mL capacity, type I glass vial sealed with a bromobutyl rubber stopper with polymer coating and aluminium seal with burgundy polypropylene flip-off cap containing 60 mg of sotatercept.

Prefilled syringe (type I glass cartridge closed with a bromobutyl rubber stopper) with 1.3 mL of solvent.

Winrevair powder and solvent for solution for injection is available as the following pack sizes:

• Kits containing 1 vial with 45 mg powder, 1 prefilled syringe with 1.0 mL solvent, 1 dosing syringe with 0.1 mL graduations, 1 vial adaptor (13 mm), 1 needle for injection and 4 alcohol wipes.
• Kits containing 2 vials with 45 mg powder, 2 prefilled syringe s with 1.0 mL solvent, 1 dosing syringe with 0.1 mL graduations, 2 vial adaptors (13 mm), 1 needle for injection and 8 alcohol wipes.
• Kits containing 1 vial with 60 mg powder, 1 prefilled syringe with 1.3 mL solvent, 1 dosing syringe with 0.1 mL graduations, 1 vial adaptor (13 mm), 1 needle for injection and 4 alcohol wipes.
• Kits containing 2 vials with 60 mg powder, 2 prefilled syringe s with 1.3 mL solvent, 1 dosing syringe with 0.1 mL graduations, 2 vial adaptors (13 mm), 1 needle for injection and 8 alcohol wipes.

Not all pack sizes may be marketed.

Selecting the appropriate product kit

If a patient’s weight requires the use of two 45 mg or two 60 mg vials, a 2-vial kit should be used instead of two 1-vial kit to eliminate the need for multiple injections (see section 6.5).

Reconstitution and administration instructions

Winrevair powder and solvent for solution for injection should be reconstituted before use and administered as a single injection according to patient weight (see section 4.2).

See the separate Instructions for Use booklet provided in the kit for detailed step by step instructions on how to prepare and administer the medicinal product. An overview of the reconstitution and administration instructions is provided below.

Reconstitution:

• Remove the kit from the refrigerator and wait 15 minutes to allow the prefilled syringe(s) and medicinal product to come to room temperature prior to preparation.
• Check the vial to ensure the medicinal product is not expired. The powder should be white to off-white and may look like a whole or broken up cake.
• Remove the lid from the vial containing the powder and swab the rubber stopper with an alcohol wipe.
• Attach the vial adaptor to the vial.
• Visually inspect the prefilled syringe for any damage or leaks and the sterile water inside to ensure there are no visible particles.
• Break off the cap of the prefilled syringe and attach the syringe to the vial adaptor.
• Inject all of the sterile water from the attached syringe into the vial containing the powder:
  • The prefilled syringe provided with the vial 45 mg contains 1.0 mL of sterile water.
  • The prefilled syringe provided with the vial 60 mg contains 1.3 mL of sterile water. After reconstitution, the 45 mg vial can only provide up to a dose of 0.9 mL of medicinal product and the 60 mg vial can only provide up to a dose of 1.2 mL of medicinal product. The final concentration after reconstitution is 50 mg/mL.
• Gently swirl the vial to reconstitute the medicinal product. D o not shake or vigorously agitate.
• Allow the vial to stand for up to 3 minutes to allow bubbles to disappear.
• Visually inspect the reconstituted solution. When properly mixed, the reconstituted solution should be clear to opalescent and colourless to slightly brownish-yellow, and should not have clumps or powder.
• Unscrew the syringe from the vial adaptor and discard the emptied syringe into a sharps container.
• If prescribed a 2-vial kit, repeat the steps within this section to prepare the second vial.
• Use the reconstituted solution as soon as possible, but no later than 4 hours after reconstitution.

Dosing syringe preparation:

• Before preparing the dosing syringe, visually inspect the reconstituted solution. The reconstituted solution should be clear to opalescent and colourless to slightly brownish-yellow, and should not have clumps or powder.
• Swab the vial adaptor with an alcohol wipe.
• Remove the dosing syringe from its packaging and attach the syringe to the vial adaptor.
• Turn the syringe and vial upside-down and withdraw the appropriate volume for injection, based on the patient’s weight.
  • If the dose amount requires the use of two vials, withdraw the entire contents of the first vial and slowly transfer the entire contents into the second vial, to ensure dose accuracy.
  • Turn the syringe and vial upside-down and withdraw the required amount of medicinal product.
• If necessary, push the plunger in to remove excess medicinal product or air from the syringe.
• Remove the syringe from the vial adaptor and attach the needle.

Administration:

Winrevair is to be administered as a single subcutaneous injection.

• Select the injection site on the abdomen (at least 5 cm away from navel), upper thigh, or upper arm and swab with an alcohol wipe. Select a new site for each injection that is not scarred, tender, or bruised.
  • For administration by the patient or caregiver, train them to inject only in the abdomen or upper thigh (see “Instructions for Use” booklet).
• Perform subcutaneous injection.
• Discard the emptied syringe into a sharps container. Do not reuse the syringe.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

See section 4.4 for instructions on the traceability of b iological medicinal products.