Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Mannitol, Glycine, Disodium phosphate dihydrate, Sodium dihydrogen phosphate dihydrate.

6.2   Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
Reconstituted solution for infusion

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C.
From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C.

6.4   Special precautions for storage

Store and transport refrigerated (2°C - 8°C). Do not freeze.
Store in the original package in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5   Nature and contents of container

10 mL vial (Type I glass) with a bromobutyl rubber stopper, an aluminium seal and a polypropylene flip off cap.
Each vial contains 10 mg of velmanase alfa.
Pack sizes of 1, 5 or 10 vials per carton.
Not all pack sizes may be marketed.

6.6   Special precautions for disposal and other handling

Lamzede requires reconstitution and is intended for intravenous infusion only.
Each vial is for single use only.
Instructions for reconstitution and administration
Lamzede should be reconstituted and administrated by a healthcare professional.
Aseptic technique is to be used during preparation. Filter needles must not be used during preparation.
 a)    The number of vials to be used should be calculated based on the individual patient’s weight.
The recommended dose of 1 mg/kg is determined using the following calculation: -     Patient’s weight (kg) × dose (mg/kg) = Patient dose (in mg).
-     Patient dose (in mg) divided by 10 mg/vial (content of one vial) = number of vials to reconstitute. If the number of calculated vials includes a fraction, it should be rounded up to the next whole number.
-     Approximately 30 minutes prior to reconstitution, the required number of vials should be removed from the refrigerator. The vials should reach ambient temperature (between 15°C and 25°C) prior to reconstitution.
Each vial is reconstituted by slowly injecting 5 mL of water for injections to the inside of the wall of each vial. Each mL of reconstituted solution contains 2 mg of velmanase alfa. Only the volume corresponding to the recommended dose should be administered.
Example:
-     Patient’s weight (44 kg) × dose (1 mg/kg) = Patient dose (44 mg).
-     44 mg divided by 10 mg/vial = 4.4 vials, therefore, 5 vials should be reconstituted.
-     From the total reconstituted volume, only 22 mL (corresponding to 44 mg) should be administered.
 b)    The powder should be reconstituted in the vial by a slow drop-wise addition of the water for injections down the inside of the vial and not directly onto the lyophilised powder. Forcefully ejecting the water for injections from the syringe onto the powder should be avoided to minimise foaming. The reconstituted vials should stand on the table for about 5-10 minutes.
Thereafter each vial should be tilted and rolled gently for 15-20 seconds to enhance the dissolution process. The vial should not be inverted, swirled, or shaken.
 c)    An immediate visual inspection of the solution for particulate matter and discoloration should be performed after reconstitution. The solution should be clear and not used if opaque particles are observed or if the solution is discoloured. Due to the nature of the medicinal product, the reconstituted solution may occasionally contain some proteinaceous particles in form of thin white strands or translucent fibers which will be removed by the in-line filter during infusion (see point e).
 d)    The reconstituted solution is to be slowly withdrawn from each vial with caution to avoid foaming in the syringe. If the volume of the solution exceeds one syringe capacity, the required number of syringes should be prepared in order to replace the syringe quickly during the infusion.
 e)    The reconstituted solution should be administered using an infusion set equipped with a pump and an in-line low protein-binding 0.22 μm filter.
The total volume of infusion is determined by the patient’s weight and should be administrated over a minimum of 50 minutes. For patients weighing less than 18 kg, and receiving less than 9 mL reconstituted solution, the infusion rate should be calculated so that the infusion time is ≥50 minutes. The maximum infusion rate is 25 mL/hour (see section 4.2). The infusion time can be calculated from the following table:


Patient   Dose   Maximum    Minimum           Patient   Dose   Maximum    Minimum weight    (mL)   infusion   infusion          weight    (mL)   infusion   infusion (kg)             rate       time (min)        (kg)             rate       time (min) (mL/h)                                        (mL/h)
5         2.5    3          50                53        26.5   25         64 6         3      3.6        50                54        27     25         65 7         3.5    4.2        50                55        27.5   25         67 8         4      4.8        50                56        28     25         67 9         4.5    5.4        50                57        28.5   25         68 10        5      6          50                58        29     25         70 11        5.5    6.6        50                59        29.5   25         71 12        6      7.2        50                60        30     25         72 13        6.5    7.8        50                61        30.5   25         73 14        7      8.4        50                62        31     25         74 15        7.5    9          50                63        31.5   25         76 16        8      9.6        50                64        32     25         77 17        8.5    10.2       50                65        32.5   25         78 18        9      10.8       50                66        33     25         79 19        9.5    11.4       50                67        33.5   25         80 20        10     12         50                68        34     25         82
21        10.5   12.6       50                69        34.5   25         83
22        11     13.2       50                70        35     25         84
23        11.5   13.8       50                71        35.5   25         85
24        12     14.4       50                72        36     25         86
25        12.5   15         50                73        36.5   25         88
26        13     15.6       50                74        37     25         89
27        13.5   16.2       50                75        37.5   25         90
28        14     16.8       50                76        38     25         91
29        14.5   17.4       50                77        38.5   25         92
30        15     18         50                78        39     25         94 31        15.5   18.6       50                79        39.5   25         95 32        16     19.2       50                80        40     25         96 33        16.5   19.8       50                81        40.5   25         97 34        17     20.4       50                82        41     25         98 35        17.5   21         50                83        41.5   25         100 36        18     21.6       50                84        42     25         101 37        18.5   22.2       50                85        42.5   25         102 38        19     22.8       50                86        43     25         103 39        19.5   23.4       50                87        43.5   25         104 40        20     24         50                88        44     25         106
41        20.5   24.6       50                89        44.5   25         107
42        21     25         50                90        45     25         108
43        21.5   25         52                91        45.5   25         109
44        22     25         53                92        46     25         110
45        22.5   25         54                93        46.5   25         112
46        23     25         55                94        47     25         113
47        23.5   25         56                95        47.5   25         114
48        24     25         58                96        48     25         115
49        24.5   25         59                97        48.5   25         116
50        25     25         60                98        49     25         118 Patient    Dose      Maximum       Minimum           Patient    Dose     Maximum       Minimum weight     (mL)      infusion      infusion          weight     (mL)     infusion      infusion (kg)                 rate          time (min)        (kg)                rate          time (min) (mL/h)                                              (mL/h)
51         25.5      25            61                99         49.5     25            119 52         26        25            62
 f)    When the last syringe is empty, the dose syringe is replaced with a 20 mL syringe filled with sodium chloride 9 mg/mL (0.9%) solution for injection. A volume of 10 mL sodium chloride solution should be administered through the infusion system to infuse the remaining fraction of Lamzede in the line to the patient.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.