ADYNOVATE

What it is

ADYNOVATE is rurioctocog alfa pegol, a recombinant coagulation factor VIII with PEGylation, supplied in single-use vials containing nominal potencies of 250, 500, 750, 1000, 1500, 2000 or 3000 IU per vial with a diluent vial containing sterile water for injections for reconstitution. ADYNOVATE is formulated as a sterile, non-pyrogenic, white to off-white, lyophilised powder for intravenous injection after reconstitution with water for injections. ADYNOVATE is a full-length recombinant human coagulation factor VIII with an extended half-life, produced by recombinant DNA technology from a Chinese hamster ovary cell line, with the octocog alfa molecule then covalently conjugated with a PEG reagent to increase the plasma half-life through reduction of receptor-mediated clearance.

Approved indications

ADYNOVATE is a long-acting antihaemophilic factor (recombinant) indicated in haemophilia A (congenital factor VIII deficiency) patients for: — Control and prevention of bleeding episodes — Routine prophylaxis to prevent or reduce the frequency of bleeding episodes — Perioperative management (surgical prophylaxis)

Dosing overview

For long-term prophylaxis, the recommended dose is 40 to 50 IU per kg bodyweight of ADYNOVATE twice weekly in 3 to 4 day intervals, with dose and/or frequency adjusted to provide necessary coverage to prevent bleeding, and in some cases doses up to 60 IU per kg can be used. For prophylactic therapy in patients under the age of 12, the recommended dose is 40 to 60 IU per kg bodyweight of ADYNOVATE twice weekly in 3 to 4 day intervals, and in some cases doses up to 80 IU per kg can be used. On-demand treatment dosing is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/dL, calculated using the formula: Required units (IU) = body weight (kg) × desired factor VIII rise (%) × 0.5. For early haemarthrosis, muscle bleeding or oral bleeding, factor VIII level should not fall below 20–40% with repeat injections every 12 to 24 hours for at least 1 day; for more extensive haemarthrosis, muscle bleeding or haematoma, 30–60% with repeat injections every 12 to 24 hours for 3–4 days or more; and for life-threatening haemorrhages, 60–100% with repeat injections every 8 to 24 hours until threat is resolved. For minor surgery including tooth extraction, factor VIII level should be 30–60% every 24 hours for at least 1 day until healing is achieved, and for major surgery, 80–100% pre- and postoperatively with repeat injections every 8 to 24 hours until adequate wound healing then continue therapy for at least another 7 days to maintain a factor VIII activity of 30% to 60%.

Key safety warnings

Hypersensitivity reactions are possible with ADYNOVATE, including allergic-type hypersensitivity reactions and anaphylaxis, which have been reported with recombinant antihaemophilic factor VIII products; administration should be immediately discontinued and treatment initiated as clinically appropriate if hypersensitivity reactions occur. The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication, with risk highest within the first 20 exposure days, and rarely developing after the first 100 exposure days; cases of recurrent inhibitor have been observed after switching from one factor VIII product to another in previously treated patients, therefore all patients should be monitored carefully for inhibitor occurrence following any product switch. In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase the cardiovascular risk, and if a central venous access device is required, the risk of device-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.

Contraindications

Known life-threatening hypersensitivity reaction, including anaphylaxis, to ADYNOVATE, to the parent molecule ADVATE (octocog alfa), to mouse or hamster protein, or other constituents of ADYNOVATE.

PBS listing

No information regarding PBS listing is available in the provided source documents.

Regulatory history

ADYNOVATE rurioctocog alfa pegol was first registered on the ARTG on 21 March 2017, with initial registrations for the 250 IU, 500 IU, 1000 IU and 2000 IU strengths, followed by registrations for the 750 IU, 1500 IU and 3000 IU strengths on 29 January 2019.