Haegarda^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

CSL Behring, GmbH (Germany)

ATC Code

B06AC01 (Human C1-esterase inhibitor (isolated from plasma))

Active Substance

Human C1-esterase inhibitor (Grouping name)

Dosage Forms

	Haegarda®	Lyophilisate for preparation of solution for subcutaneous administration 2000 IU: 1 fl. in a set with solvent
		Lyophilisate for preparation of solution for subcutaneous administration 3000 IU: 1 fl. in a set with solvent

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for s.c. administration as a white amorphous mass; reconstituted solution: colorless, clear or slightly opalescent; solvent: colorless clear liquid.

Excipients: glycine – 40 mg, sodium chloride – 34 mg, sodium citrate dihydrate – 10 mg*.

* calculated as sodium citrate, anhydrous basis.

The total protein content in 1 ml of the reconstituted drug solution is 65 mg/ml.

2000 IU lyophilisate – 1 colorless glass vial with a capacity of 20 ml in a set with solvent “Water for injections” 4 ml (1 colorless glass vial), 1 solvent addition device with a built-in 15 µm filter “Mix-2Vial^® 20/20″ in a blister and 1 cardboard pack with a kit for subcutaneous administration of the drug (1 disposable 5 ml syringe, 1 butterfly needle, 2 disinfectant wipes in individual sealed packages and 1 non-sterile adhesive plaster) with first opening control in a cardboard pack with first opening control.

Lyophilisate for preparation of solution for s.c. administration as a white amorphous mass; reconstituted solution: colorless, clear or slightly opalescent; solvent: colorless clear liquid.

Excipients: glycine – 60 mg, sodium chloride – 51 mg, sodium citrate dihydrate – 15 mg*.

* calculated as sodium citrate, anhydrous basis.

The total protein content in 1 ml of the reconstituted drug solution is 65 mg/ml.

3000 IU lyophilisate – 1 colorless glass vial with a capacity of 30 ml in a set with solvent “Water for injections” 5.6 ml (1 colorless glass vial), 1 solvent addition device with a built-in 15 µm filter “Mix-2Vial^® 20/20″ in a blister and 1 cardboard pack with a kit for subcutaneous administration of the drug (1 disposable 10 ml syringe, 1 butterfly needle, 2 disinfectant wipes in individual sealed packages and 1 non-sterile adhesive plaster) with first opening control in a cardboard pack with first opening control.

Clinical-Pharmacological Group

Drug with antiallergic action

Pharmacotherapeutic Group

Other hematological agents; agents used in hereditary angioedema

Pharmacological Action

Agent for the treatment of hereditary angioedema. C1-esterase inhibitor is a plasma glycoprotein with a molecular weight of 105 kD and a carbohydrate fragment that makes up 40%.

The concentration of C1-esterase inhibitor in human plasma is about 240 mg/l. In addition to plasma, it is present in the placenta, liver cells, monocytes, and platelets.

C1-esterase inhibitor is included in the serine protease inhibitor (serpin) system of human plasma, as are other proteins such as antithrombin III, alpha-2-antiplasmin, alpha-1-antitrypsin.

Under physiological conditions, C1-esterase inhibitor blocks the classical pathway of the complement system by inactivating the enzymatically active components C1s and C1r. The active enzyme forms a complex with the inhibitor in a stoichiometric structure of 1:1. Furthermore, C1-esterase inhibitor is the most important inhibitor of the contact activation process of coagulation, inhibiting factor XIIa and its fragments. In doing so, being an alpha2-macroglobulin, it acts as the main inhibitor of plasma kallikrein.

In hereditary angioedema, the therapeutic effect of conestat alfa is due to the replacement of activity in C1-esterase inhibitor deficiency.

Pharmacokinetics

After IV administration, the maximum activity of C1-esterase inhibitor in plasma was reached after 0.8 h. Insignificant interindividual differences were observed among different patients. The mean T_1/2 was 36.1 h. In children, T_1/2 was shorter than in adults and was 32.9 h.

Indications

Hereditary angioedema types I and II – treatment and prevention of acute attacks (according to the dosage form used).

ICD codes

Dosage Regimen

Initiate treatment under the supervision of a physician experienced in managing C1-esterase inhibitor deficiency.

Administer subcutaneously twice weekly. The standard prophylactic dosage is 60 IU per kg of body weight.

Calculate the exact dose based on the patient’s body weight and the available vial strengths of 2000 IU or 3000 IU.

Do not exceed a single injection volume of 8 mL. For doses requiring more than 8 mL, divide the total volume and administer at separate injection sites.

Rotate injection sites with each administration; acceptable areas include the abdomen, thighs, buttocks, or upper arms.

Reconstitute the lyophilisate strictly according to the provided instructions using the supplied Water for Injections and the Mix-2Vial^® transfer device.

Inspect the reconstituted solution visually for particulate matter and discoloration before administration. The solution must be colorless, clear, and essentially free of particles.

Discard any unused solution. Do not mix with other medicinal products or solvents.

Monitor patients for signs of hypersensitivity reactions during and after administration.

Adverse Reactions

From the cardiovascular system rarely – development of thrombosis, tachycardia, arterial hyper- and hypotension, flushing.

Allergic reactions: rarely – allergic or anaphylactic reactions; dyspnea, headache, dizziness, nausea, rash; very rarely – shock.

General reactions rarely – increased body temperature.

Contraindications

Hypersensitivity to human C1-esterase inhibitor, children under 2 years (depending on the dosage form used).

Use in Pregnancy and Lactation

Use during pregnancy is only possible in cases of extreme necessity.

It is not known whether conestat alfa is excreted in breast milk. However, since conestat alfa has a high molecular weight, penetration into breast milk is unlikely. If use during lactation is necessary, breastfeeding should be discontinued.

Pediatric Use

Used in children according to indications and in a dosage form appropriate for age.

Special Precautions

Patients with a tendency to allergies should be prophylactically administered antihistamines and corticosteroids.

If allergic or anaphylactic reactions develop, administration of conestat alfa should be stopped immediately (i.e., the injection/infusion should be interrupted) and appropriate treatment should be prescribed. Therapeutic measures depend on the type and severity of the adverse effect. Standard anti-shock therapy should be applied.

Patients with laryngeal edema require careful observation and emergency therapy.

Use in capillary leak syndrome is not recommended.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°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.