Fabrazyme^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Sanofi, B.V. (Netherlands)

Manufactured By

Genzyme Ireland Limited (Ireland)

ATC Code

A16AB04 (Agalsidase beta)

Active Substance

Agalsidase beta (Rec.INN registered by WHO)

Dosage Form

Fabrazyme®

Lyophilizate for preparation of concentrate for preparation of solution for infusion 35 mg: vial 1, 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of concentrate for preparation of solution for infusion in the form of a compact mass (lyophilisate) or a powder from white to almost white in color.

* (+ overfill of 2 mg).
After reconstitution with 7.2 ml of water for injections, each vial of the drug contains 5 mg/ml (35 mg/7 ml) of agalsidase beta.

Excipients: mannitol, sodium dihydrogen phosphate monohydrate, sodium hydrogen phosphate heptahydrate.

Glass vials with a capacity of 20 ml (1) – cardboard packs.
Glass vials with a capacity of 20 ml (5) – cardboard packs.
Glass vials with a capacity of 20 ml (10) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of hereditary enzymatic deficiency

Pharmacotherapeutic Group

Other drugs affecting the digestive system and metabolic processes, enzymes

Pharmacological Action

Agent for enzyme replacement therapy. Agalsidase beta is a recombinant human alpha-galactosidase A – an enzyme in which the amino acid sequence is the same as in the endogenous enzyme. It is obtained using recombinant DNA technology in Chinese hamster ovary cells.

Agalsidase beta is effective in Fabry disease, which is a consequence of a genetically determined (X-linked) disorder of glycosphingolipid metabolism. Deficiency of the lysosomal enzyme alpha-galactosidase A leads to progressive accumulation of glycosphingolipids, mainly globotriaosylceramide (GL-3), in the body’s tissues. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular disorders. Accumulation of GL-3 in the endothelial cells of the kidneys plays a role in the development of renal failure.

Results of preclinical and clinical studies show that Agalsidase beta catalyzes the hydrolysis of glycosphingolipids, including GL-3, which increases the formation of alpha-galactosidase A in the body of patients with Fabry disease. Agalsidase beta reduces the GL-3 content in the capillary endothelium of the kidneys, heart, and skin.

Pharmacokinetics

AUC and clearance of agalsidase beta do not increase proportionally with increasing dose, indicating nonlinear pharmacokinetics of the enzyme. Pharmacokinetic parameters are characterized by variability.

Indications

Fabry disease.

ICD codes

Dosage Regimen

Administer a dose of 1 mg/kg body weight as an intravenous infusion once every two weeks.

Calculate the total number of vials required for the dose based on the patient’s body weight and the reconstituted concentration of 5 mg/ml.

Reconstitute each 35 mg vial with 7.2 ml of Water for Injections to yield a concentration of 5 mg/ml (35 mg/7 ml). Gently roll and tilt the vial; do not shake.

Dilute the reconstituted solution in 0.9% Sodium Chloride Injection, USP, to a final volume as specified by infusion rate guidelines.

Use an in-line low protein-binding 0.2 µm filter during the infusion.

Initiate the infusion at a rate of no more than 0.25 mg/min (15 mg/hour).

Gradually increase the infusion rate in a step-wise manner if the patient tolerates the infusion well.

Monitor the patient closely for signs of infusion-associated reactions, particularly during the first few infusions.

For subsequent infusions, if the initial infusion is well-tolerated, the infusion duration may be gradually reduced, but the total duration should not be less than 1.5 hours.

If an infusion reaction occurs, decrease the infusion rate, temporarily suspend the infusion, and/or administer antipyretics, antihistamines, or corticosteroids.

Discontinue the infusion immediately and initiate appropriate emergency treatment for severe hypersensitivity or anaphylactic reactions.

Administer premedication with antipyretics and/or antihistamines to patients at risk for infusion reactions.

Adverse Reactions

Most serious reactions: allergic and anaphylactic reactions.

General reactions ≥ 5% – chills, increased body temperature, feeling of heat or cold, flushing, limb pain, chest pain, feeling of a lump in the throat, peripheral edema, back pain, pallor, facial edema, myalgia, muscle spasms.

Infections upper respiratory tract infections, lower respiratory tract infections, sinusitis, pharyngitis, fungal infections, viral infections, local infections.

Respiratory system ≥ 5% – shortness of breath, feeling of nasal congestion, respiratory congestion.

Digestive system ≥ 5% – nausea, vomiting, abdominal pain, diarrhea, toothache, dry mouth.

Central and peripheral nervous system ≥ 5% – headache, paresthesia, weakness, dizziness, drowsiness, burning sensation.

Cardiovascular system ≥ 5% – arterial hypertension, tachycardia, arterial hypotension, bradycardia, ventricular wall thinning.

Dermatological reactions ≥ 5% – itching, urticaria, rash.

Sense organs tinnitus, hypoacusis.

Other increased incidence of trauma.

Contraindications

High risk of developing severe hypersensitivity reactions to agalsidase beta.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of agalsidase beta during pregnancy have not been conducted. During pregnancy, use is possible only in cases of extreme necessity, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

It is not known whether Agalsidase beta is excreted in human breast milk. If use during lactation is necessary, the expected benefit of therapy for the mother and the potential risk for the breastfed infant should be carefully weighed.

Pediatric Use

The safety of use in children has not been established.

Geriatric Use

In patients with cardiac disorders, there may be a predisposition to a higher risk of developing severe complications of infusion reactions.

Special Precautions

The infusion should be administered in conditions that allow for emergency therapy.

If allergic and anaphylactic reactions develop, the infusion should be immediately interrupted and emergency therapy initiated.

Upon re-administration in patients with a history of anaphylactic or severe allergic reactions to the administration of agalsidase beta, the expected benefit and potential risk should be weighed. In such cases, administration should be carried out with extreme caution.

If there is a risk of developing infusion reactions, premedication with antipyretics and antihistamines should be administered.

If infusion reactions develop, the infusion rate should be reduced, the infusion should be temporarily suspended, and/or additional administration of antipyretics, antihistamines, and/or corticosteroids should be initiated. If infusion reactions persist, the infusion should be discontinued and appropriate therapy should be initiated immediately. In case of risk of developing infusion reactions, re-administration of agalsidase beta should be carried out with caution.

In patients with cardiac disorders, there may be a predisposition to a higher risk of developing severe complications of infusion reactions.

In patients predisposed to developing allergic reactions, testing for the presence of IgE antibodies should be performed and the risk and benefit of re-administration of agalsidase beta should be carefully weighed in the presence of specific IgE antibodies to agalsidase beta. If use in such cases is necessary, administration should be carried out under the direct supervision of qualified personnel.

The safety of use in children has not been established.

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.