Pharmaceutical particulars : מידע רוקחי

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Glycine
Hydrochloric acid
Water for injection
6.2 Incompatibilities
Remifentanil B.Braun should only be reconstituted and diluted with those infusion solutions recommended (see section 6.6).
It should not be reconstituted, diluted or mixed with Lactated Ringer's Injection or Lactated Ringer's and 5% Dextrose Injection.
Remifentanil B.Braun should not be mixed with propofol in the same infusion bag prior to administration.
Administration of Remifentanil B.Braun into the same intravenous line with blood/serum/plasma is not recommended. Non-specific esterases in blood products may lead to the hydrolysis of remifentanil to its inactive metabolite.
Remifentanil B.Braun should not be mixed with other therapeutic agents prior to administration.

6.3 Shelf life
The expiry date of the product is indicated on the packaging materials.

6.4 Special precautions for storage
Store at or below 25°C.
Do not refrigerate or freeze.
The reconstituted solution of Remifentanil B.Braun is chemically and physically stable for 24 hours at room temperature (25°C). From a microbiological point of view, the product should be 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 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Any unused material should be discarded.

6.5 Nature and contents of container
Remifentanil B.Braun for Injection 1 mg for intravenous use is available as 1 mg of Remifentanil lyophilised powder in 4 ml vials, in cartons of 5.
Remifentanil B.Braun for Injection 2 mg for intravenous use is available as 2 mg of Remifentanil lyophilised powder in 6 ml vials, in cartons of 5.
Remifentanil B.Braun for Injection 5 mg for intravenous use is available as 5 mg of Remifentanil lyophilised powder in 10 ml vials, in cartons of 5.

6.6 Special precautions for disposal
Remifentanil B.Braun should be prepared for intravenous use by adding, as appropriate 1, 2, or 5 ml of diluent (according to the list below) to give a reconstituted solution with a concentration of 1 mg/ml remifentanil. The reconstituted solution is clear, colourless, and practically free from particulate material. After reconstitution, visually inspect the product (where the container permits) for particulate material, discolouration or damage of container.
Discard any solution where such defects are observed. Reconstituted product is for single use only. Any unused material should be discarded.

Remifentanil B.Braun should not be administered by manually-controlled infusion without further dilution to concentrations of 20 to 250 micrograms/ml (50 micrograms/ml is the recommended dilution for adults).

The dilution is dependent upon the technical capability of the infusion device and the anticipated requirements of the patient.

One of the following diluents should be used for reconstitution:
Water for Injections
Glucose 5% solution for injection
Glucose 5% and Sodium Chloride 0.9% solution for injection
Sodium Chloride 0.9% solution for injection
Sodium Chloride 0.45% solution for injection

After reconstitution, Remifentanil B. Braun may be further diluted.
Remifentanil has been shown to be compatible with the following intravenous fluids when administered into a running IV catheter:
Lactated Ringer's solution for injection
Lactated Ringer's and Glucose 5% solution for injection

Remifentanil has been shown to be compatible with propofol when administered into a running IV catheter.

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

The following tables give guidelines for infusion rates of Remifentanil B.Braun for manually controlled infusion:
Table 1. Remifentanil B.Braun for Injection Infusion Rates (ml/kg/h) 
Drug       Infusion Delivery Rate (ml/kg/h) for Solution Concentrations of Delivery 20               25                50               250
Rate     micrograms/ml micrograms/ml micrograms/ml micrograms/ml
1 mg/50 ml       1 mg/40 ml        1 mg/20 ml       10 mg/40 ml
0.0125       0.038             0.03             0.015             Not recommended
0.025       0.075             0.06              0.03             Not recommended
0.05        0.15             0.12              0.06            0.012 0.075        0.23             0.18              0.09            0.018 0.1         0.3             0.24              0.12            0.024
0.15        0.45             0.36              0.18            0.036 0.2         0.6             0.48              0.24            0.048
0.25        0.75              0.6               0.3             0.06 0.5         1.5              1.2               0.6             0.12
0.75        2.25              1.8               0.9             0.18 1.0         3.0              2.4               1.2             0.24
1.25        3.75              3.0               1.5              0.3 1.5         4.5              3.6               1.8             0.36
1.75        5.25              4.2               2.1             0.42 2.0         6.0              4.8               2.4             0.48

Table 2. Remifentanil B.Braun for Injection Infusion Rates (ml/h) for a 20 micrograms/ml Solution

Infusion                         Patient Weight (kg)
Rate         5       10        20       30       40        50      60 (micrograms
/kg/ min)
0.0125      0.188    0.375     0.75     1.125      1.5    1.875     2.25 0.025      0.375    0.75       1.5      2.25      3.0    3.75       4.5 0.05      0.75      1.5       3.0       4.5      6.0     7.5       9.0 0.075      1.125    2.25       4.5      6.75      9.0    11.25     13.5 0.1       1.5      3.0       6.0       9.0     12.0    15.0      18.0 0.15      2.25      4.5       9.0      13.5     18.0    22.5      27.0 0.2       3.0      6.0      12.0      18.0     24.0    30.0      36.0 0.25      3.75      7.5      15.0      22.5     30.0    37.5      45.0 0.3       4.5      9.0      18.0      27.0     36.0    45.0      54.0 0.35      5.25     10.5      21.0      31.5     42.0    52.5      63.0 0.4       6.0     12.0      24.0      36.0     48.0    60.0      72.0 Table 3. Remifentanil B.Braun for Injection Infusion Rates (ml/h) for a 25 micrograms/ml Solution

Infusion Rate                                         Patient Weight (kg) (micrograms      10         20         30       40       50      60      70     80    90      100 /kg/min)
0.0125      0.3          0.6         0.9     1.2      1.5     1.8    2.1    2.4    2.7     3.0 0.025      0.6          1.2         1.8    2.4       3.0     3.6    4.2     4.8   5.4     6.0 0.05       1.2          2.4        3.6      4.8      6.0     7.2    8.4     9.6   10.8    12.0 0.075      1.8         3.6          5.4     7.2      9.0    10.8   12.6    14.4   16.2    18.0 0.1       2.4          4.8         7.2     9.6     12.0    14.4   16.8    19.2   21.6    24.0 0.15       3.6          7.2        10.8    14.4     18.0    21.6   25.2    28.8   32.4    36.0 0.2       4.8          9.6        14.4    19.2     24.0    28.8   33.6    38.4   43.2    48.0 
Table 4. Remifentanil B.Braun for Injection Infusion Rates (ml/h) for a 50 micrograms/ml Solution

Infusion Rate                                     Patient Weight (kg) (micrograms/kg/        30          40          50     60     70     80          90     100 min)
0.025         0.9         1.2         1.5    1.8  2.1   2.4                2.7     3.0 0.05          1.8         2.4         3.0    3.6  4.2   4.8                5.4     6.0 0.075         2.7         3.6         4.5    5.4  6.3   7.2                8.1     9.0 0.1          3.6         4.8         6.0    7.2  8.4   9.6               10.8    12.0 0.15          5.4         7.2         9.0   10.8 12.6  14.4               16.2    18.0 0.2          7.2         9.6        12.0 14.4 16.8    19.2               21.6    24.0 0.25          9.0        12.0        15.0 18.0 21.0    24.0               27.0    30.0 0.5         18.0        24.0        30.0 36.0 42.0    48.0               54.0    60.0 0.75         27.0        36.0        45.0 54.0 63.0    72.0               81.0    90.0 1.0         36.0        48.0        60.0 72.0 84.0    96.0              108.0   120.0 1.25         45.0        60.0        75.0 90.0 105.0 120.0               135.0   150.0 1.5         54.0        72.0        90.0 108.0 126.0 144.0              162.0   180.0 1.75         63.0        84.0        105.0 126.0 147.0 168.0             189.0   210.0 2.0         72.0        96.0        120.0 144.0 168.0 192.0             216.0   240.0

Table 5. Remifentanil B.Braun for Injection Infusion Rates (ml/h) for a 250 micrograms/ml Solution

Infusion Rate                                     Patient Weight (kg) (micrograms/kg/ 30                40           50    60     70     80          90      100 min)
0.1      0.72               0.96        1.20 1.44   1.68 1.92 2.16 2.40 0.15      1.08               1.44        1.80 2.16 2.52 2.88 3.24 3.60 0.2      1.44               1.92        2.40 2.88 3.36 3.84 4.32 4.80 0.25      1.80               2.40        3.00 3.60 4.20 4.80 5.40 6.00 0.5      3.60               4.80        6.00 7.20 8.40 9.60 10.80 12.00 0.75      5.40               7.20        9.00 10.80 12.60 14.40 16.20 18.00 1.0      7.20               9.60        12.00 14.40 16.80 19.20 21.60 24.00 1.25         9.00    12.00   15.00   18.00   21.00   24.00   27.00   30.00 1.5         10.80   14.40   18.00   21.60   25.20   28.80   32.40   36.00 1.75         12.60   16.80   21.00   25.20   29.40   33.60   37.80   42.00 2.0         14.40   19.20   24.00   25.20   33.60   38.40   43.20   48.00