As agalsidase beta (r-hαGAL) is a recombinant protein, the formation of IgG antibodies is expected in patients with little or no enzymatic activity. Most patients developed IgG antibodies to r-hαGAL usually within 3 months after the first infusion of Fabrazyme. Over time, the majority of seropositive patients in clinical trials demonstrated either a decrease in titres (> 4-fold decrease in titer from the peak to the last measurement) (40% of patients),or no response (antibodies were not detected, as confirmed by 2 consecutive radioimmunoprecipitation (RIP) reactions) (14% of patients) or demonstrated a continuous antibody titer (35% of patients).
Patients with antibodies to r-hαGAL are more likely to develop RSI, which is any side effect that developed on the day of the infusion. In these patients, repeated administration of agalsidase beta should be carried out with caution (see section "Side effect"). It is necessary to regularly monitor antibody titers.
In clinical trials, 67% of patients experienced at least one RCI (see the "Side effect" section). The incidence of RSI decreased with time. Patients with developed lung or moderate RSI with agalsidase beta during clinical trials continued therapy after reducing infusion rate (-0.15 mg / min; 10 mg / h) and / or after premedication with antihistamines, paracetamol, ibuprofen and / or glucocorticosteroids.
As with intravenous administration of any protein preparation, allergic hypersensitivity reactions are possible.
In a small number of patients, reactions resembling immediate type hypersensitivity reactions (type I) were noted. In the case of a severe allergic reaction or anaphylactic-type reaction, the immediate administration of Fabrazyme® and take appropriate action. It is necessary to monitor the current medical standards of emergency therapy. In clinical studies, after conducting provocative samples, repeated administration of Fabrazyme® to patients with a positive IgE titer and a positive skin test to Fabrazyme®. In this study, repeated administration of the drug was first performed at a lower dose and at a lower rate (1/2 therapeutic dose and 1/25 of the initial standard recommended rate). With normal infusion tolerance, the dose can be increased to a therapeutic dose of 1 mg / kg, and the infusion rate can be gradually increased as the patient is tolerated.
The effect of treatment with Fabrazyme® on the kidneys can be reduced in patients with severe kidney disease. There were no studies of the effect of Fabrazyme on reproductive function.
Instructions on the use, handling and destruction of drug residues
Lyophilizate for the preparation of concentrate for the preparation of solution for infusions should be restored with water for injection, diluted with 0.9% sodium chloride solution for intravenous administration and then administered by intravenous infusion.
Follow the rules of asepsis. Determine the number of reconstituted vials according to the individual body weight of the patient, remove them from the refrigerator and leave them to warm to room temperature, for about 30 minutes. Each vial of Fabrazyme® is intended for single use only.
Recovery (preparation of concentrate)
Each vial of Fabrazyme® is reconstituted with 7.2 ml of water for injection. Avoid foaming and rapid addition of water to the lyophilizate. Water for injection should be added by slowly digging to the wall of the vial with the drug, avoiding its addition directly to the lyophilizate. Carefully tilt and turn each bottle. The bottle should not be turned, rotated or shaken.
The reconstituted solution (concentrate) contains 5 mg / ml agalicidase beta, and is a clear and colorless solution. The pH of the concentrate is about 7.Before further dilution, visually inspect the vial for particles and discoloration. In the presence of particles or when changing colors, concentrate should not be used.
After reconstitution (preparation of the concentrate), it is recommended that the contents of the vials be quickly diluted to prevent the formation of protein lumps that occur over time.
Any unused product or waste should be disposed of in accordance with local requirements.
Dilution of concentrate
Before diluting the concentrate from the infusion container, it is recommended to remove the volume of 0.9% sodium chloride solution equal to the volume of the concentrate.
Remove air from the infusion container to minimize the interaction of air and solution.
From each vial, 7.0 ml of concentrate (equivalent to 35 mg) are slowly withdrawn to the total volume required to provide the patient's dose. Do not use a needle with a filter and avoid foaming.
Slowly inject the concentrate directly into a 0.9% solution of sodium chloride (the tip of the needle should be in solution) until the concentration of the finished solution is 0.05 -0.7 mg / ml.Based on the individual dose of the patient, the total volume of 0.9% of the infusion solution of sodium chloride (50 - 500 ml) is determined. For doses below 35 mg, a minimum of 50 ml is used, a minimum of 100 ml is used for doses of 35 to 70 mg, a minimum of 250 ml is used for doses of 70-100 mg, and 500 ml of 0.9% sodium chloride infusion solution is used for doses greater than 100 mg. Carefully turn over or lightly press on the surface of the infusion container to mix the diluted solution. Do not shake or vigorously shake the contents of the infusion container.
Introduction
A diluted solution is recommended to be injected through a 0.2 μm filter with a low level of protein binding to remove any protein particles and to avoid any loss of agsidase beta activity. The initial infusion rate should be no more than 0.25 mg / min (15 mg / hour) to minimize the possible development of RSI. After determining the tolerability of the drug by the patient, the infusion rate can be gradually increased with subsequent infusions.