Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Glycine
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment if needed)


6.2   Incompatibilities
Ultiva should only be reconstituted and diluted with those infusion solutions recommended (see section 6).

It should not be reconstituted, diluted or mixed with Lactated Ringer's Injection or Lactated Ringer's and 5% Dextrose Injection.

Ultiva should not be mixed with propofol in the same infusion bag prior to administration.

Administration of Ultiva 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.

Ultiva 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 label and packaging.

6.4   Special precautions for storage

Do not store above 25ºC.
The reconstituted solution of Ultiva is chemically and physically stable for 24 hours at room temperature (25°C). However, Ultiva does not contain an antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions, reconstituted product should be used promptly, and any unused material discarded.

6.5   Nature and contents of container

Ultiva 5 mg is available as 5 mg of Remifentanil lyophilised powder in 10 ml vials, in cartons of 5.

6.6   Special precautions for disposal and other handling

Ultiva 5mg should be prepared for intravenous use by adding, as appropriate, 5 ml of diluent to give a reconstituted solution with a concentration of 1mg/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.

Ultiva 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 IV fluids listed below should be used for dilution: 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 dilution, visually inspect the product to ensure it is clear, colourless, practically free from particulate matter and the container is undamaged. Discard any solution where such defects are observed.

Ultiva 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

Ultiva 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 Ultiva for manually- controlled infusion:


Table 1.        Ultiva for Injection Infusion Rates (ml/kg/h)
Drug Delivery        Infusion Delivery Rate (ml/kg/h) for Solution Concentrations of Rate
(micrograms/kg/       25 micrograms/ml            50 micrograms/ml      250 micrograms/ min)                                                                     ml 1 mg/40 ml               1 mg/20 ml
10 mg/40 ml
0.0125                   0.03                     0.015          Not recommended 0.025                    0.06                     0.03           Not recommended 0.05                     0.12                     0.06                    0.012 0.075                    0.18                     0.09                    0.018 0.1                      0.24                     0.12                    0.024 0.15                     0.36                     0.18                    0.036 0.2                      0.48                     0.24                    0.048 0.25                     0.6                      0.3                     0.06 0.5                      1.2                      0.6                     0.12 0.75                     1.8                      0.9                     0.18 1.0                      2.4                      1.2                     0.24 1.25                     3.0                      1.5                     0.3 1.5                      3.6                      1.8                     0.36 1.75                     4.2                      2.1                     0.42 2.0                      4.8                      2.4                     0.48


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

Infusion                                     Patient Weight (kg)
Rate(microgram s/kg/min)            5         10        20          30         40     50            60 
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.        Ultiva 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.        Ultiva for Injection Infusion Rates (ml/h) for a 50 micrograms/ml Solution 
Infusion                                               Patient Weight (kg) Rate
(micrograms 30               40           50        60              70         80             90        100 /kg/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.     Ultiva for Injection Infusion Rates (ml/h) for a 250 micrograms/ml Solution

Infusion                                 Patient Weight (kg)
Rate
(micrograms 30         40       50      60        70        80       90        100 /kg/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        28.80     33.60     38.40    43.20     48.00