Adenovate^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Baxalta Innovations GmbH (Austria)

Manufactured By

Baxalta Manufacturing Sarl (Switzerland)

Solvent Manufacturer

SIEGFRIED HAMELN, GmbH (Germany)

Packaging and Quality Control Release

BAXALTA BELGIUM MANUFACTURING, SA (Belgium)

ATC Code

B02BD02 (Blood coagulation factor VIII)

Active Substance

Rurioctocog alfa pegol (Rec.INN registered by WHO)

Dosage Forms

	Adenovate®	Lyophilisate for preparation of solution for intravenous administration 250 IU: vial 1 pc.
		Lyophilisate for preparation of solution for intravenous administration 500 IU: vial 1 pc.
		Lyophilisate for preparation of solution for intravenous administration 1000 IU: vial 1 pc.
		Lyophilisate for preparation of solution for intravenous administration 1500 IU: vial 1 pc.
		Lyophilisate for preparation of solution for intravenous administration 2000 IU: vial 1 pc.
		Lyophilisate for preparation of solution for intravenous administration 3000 IU: vial 1 pc.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 50 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

250 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 100 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

500 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 200 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

1000 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 300 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

1500 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 400 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

2000 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Lyophilisate for preparation of solution for intravenous administration as a friable mass of white or almost white color; supplied solvent is a clear, colorless liquid; reconstituted solution is a clear, colorless solution without mechanical inclusions.

Concentration of Rurioctocog alfa pegol (after reconstitution in 5 ml of water for injections) – 600 IU/ml.

Excipients : mannitol – 160 mg, trehalose dihydrate – 40 mg, sodium chloride – 26.3 mg, histidine – 7.8 mg, tris(hydroxymethyl)aminomethane – 6.1 mg, calcium chloride dihydrate – 1.2 mg, polysorbate-80 – 0.5 mg, glutathione (reduced) – 0.4 mg.

Solvent water for injections – 5 ml.

3000 IU – colorless glass vials (1) in a kit with solvent (vial 5 ml 1 pc.) and BAXJECT II Hi-Flow needleless reconstitution device, butterfly needle*, disposable syringe* (10 ml), alcohol swabs* (2 pcs.), plasters* (2 pcs.) – cardboard boxes (2), combined with a transparent plastic banding tape.

The specific activity of the drug ranges from 2800 to 8000 IU per milligram of protein.
The drug is produced by recombinant technology in Chinese hamster ovary cell culture, without the addition of human or animal-derived proteins during the manufacturing process, with polyethylene glycol 20 kDa.
* placed in additional cardboard boxes.

Clinical-Pharmacological Group

Blood coagulation factor VIII preparation

Pharmacotherapeutic Group

Hemostatic agent

Pharmacological Action

Pegylated form of recombinant antihemophilic factor (octocog alfa), temporarily replaces the missing factor VIII, necessary for effective hemostasis in patients with congenital hemophilia A. Normalizes the APTT value during the period of action of the administered dose. Administration of rurioctocog alfa pegol provides an increase in the level of coagulation factor VIII in blood plasma, which allows temporary correction of the coagulation disorder in patients with hemophilia A.

Pharmacokinetics

Depending on the dose and age after infusion, C_max ranges from 117 ±16 to 145 ±29 IU/dl, V_d at steady state from 0.54 ±0.03 to 0.40 ± 0.09 dl/kg, mean plasma circulation time ranges from 18.74 ± 12.60 h, clearance – from 3.49 ± 1.21 to 2.16 ±0.75 ml/(kg×h^-1), T_1/2 from 12.99 ± 8.75 to 15.01 ± 3.89 h.

Indications

Treatment of adults and children suffering from hemophilia A (congenital deficiency of coagulation factor VIII) and previously treated, for: on-demand treatment and control of bleeding episodes; perioperative management; prophylaxis to reduce the frequency of bleeding.

Not indicated for the treatment of von Willebrand disease.

ICD codes

Dosage Regimen

Administer intravenously as a bolus infusion at a rate not exceeding 10 ml per minute.

Calculate the dose individually based on body weight, the severity of hemorrhage, and the target factor VIII level.

For on-demand treatment of bleeding episodes, administer a dose to achieve a peak factor VIII activity of 30-60% of normal for minor hemorrhages and 80-100% for major or life-threatening bleeds.

For perioperative management, administer a pre-operative dose to achieve 80-100% factor VIII activity; maintain levels at 30-60% for minor surgery and 60-80% for major surgery during the postoperative period.

For routine prophylaxis to reduce bleeding frequency, administer 40-50 IU per kilogram of body weight every other day; adjust the dosing interval based on individual pharmacokinetic response.

Determine the required number of vials using the following formula: Required IU = body weight (kg) x desired factor VIII rise (% of normal) x 0.5.

Use the reconstituted solution immediately or store at room temperature for no more than 3 hours; do not refrigerate after reconstitution.

Do not administer the drug if the solution is cloudy or contains particulate matter.

Adverse Reactions

From the blood and lymphatic system: uncommon – factor VIII inhibition.

From the organ of vision uncommon – eye hyperemia.

From the digestive system common – diarrhea, nausea.

From the immune system uncommon – hypersensitivity reactions.

From the nervous system very common – headache; common – dizziness.

From the skin and subcutaneous tissue common – skin rash; uncommon – drug dermatitis.

From the vessels uncommon – hot flush.

General uncommon – infusion reactions.

Contraindications

Hypersensitivity (including anaphylaxis) to rurioctocog alfa pegol or to octocog alfa.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding, as data are absent.

Pediatric Use

The drug is approved for use in children and adolescents under 18 years of age

Geriatric Use

Not studied.

Special Precautions

If hypersensitivity reactions develop, administration of the drug should be stopped immediately and clinically adequate treatment should be initiated.

After administration of the drug containing Rurioctocog alfa pegol, formation of neutralizing antibodies (inhibitors) to factor VIII may occur. Regular monitoring of patients for the development of factor VIII inhibitors is necessary through appropriate clinical observations and laboratory tests. If the expected level of factor VIII activity in blood plasma is not achieved, or if bleeding cannot be controlled with an adequate dose, an appropriate test should be performed to detect factor VIII inhibitors.

In patients with existing cardiovascular risk factors, factor VIII replacement therapy may increase cardiovascular risk.

During treatment, monitoring of factor VIII activity in blood plasma by a validated one-stage method should be performed to confirm the achievement and maintenance of adequate factor VIII levels.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.