Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Hydrochloric acid 0.1N
6.2   Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3   Shelf life
Before opening:
The expiry date of the product is indicated on the packaging materials 
6.4   Special precautions for storage
Before opening: Do not store above 25°C. In order to protect from light store in the original package.

After reconstitution and dilution:
From a microbiological point of view, reconstituted and subsequently diluted Cardioxane should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user, and should not be longer than 4 hours at 2°C to 8°C (in the refrigerator) with protection from light.

6.5   Nature and contents of container
Vials (Type I brown glass), containing 500 mg of powder, closed with a stopper (chlorobutyl rubber) and a cap (aluminium) with a flip-off component (polypropylene). The product is further enclosed in an outer carton. It is supplied in packs of 1 vial.

6.6   Special precautions for disposal and other handling
Recommendations for safe handling
Prescribers should refer to national or recognised guidelines on handling cytotoxic agents when using Cardioxane. Reconstitution should only be carried out by trained staff in a cytotoxic designated area. The preparation should not be handled by pregnant staff.

Use of gloves and other protective clothing to prevent skin contact is recommended. Skin reactions have been reported following contact with Cardioxane. If Cardioxane powder or solution comes into contact with the skin or mucosal surfaces, the affected area should immediately be rinsed thoroughly with water.

Preparation for intravenous administration
Reconstitution of Cardioxane
For reconstitution the contents of each vial should be dissolved in 25 ml water for injections. The vial contents will dissolve within a few minutes with gentle shaking. The resultant solution has a pH of approximately 1.6. This solution should be further diluted before administration to the patient.

Dilution of Cardioxane
To avoid the risk of thrombophlebitis at the injection site, Cardioxane should be diluted prior to infusion with one of the solutions mentioned in the table below. Preferably solutions with a higher pH should be used. The final volume is proportional to the number of vials of Cardioxane used and the amount of infusion fluid for dilution, which can be between 25 ml and 100 ml per vial.

The table below summarises the final volume and the approximate pH of reconstituted and diluted product for one vial and four vials of Cardioxane. The minimum and maximum volumes of infusion fluids to be used per vial are shown below.

Infusion fluid used    Volume of fluid used       Final             Final          pH for dilution           to dilute 1 vial of        volume            volume         (approximate) reconstituted              from 1 vial       from 4 vials
Cardioxane
Ringer lactate         25 ml                      50 ml             200 ml         2.2 100 ml                     125 ml            500 ml         3.3
0.16 M sodium          25 ml                      50 ml             200 ml         2.9 lactate*               100 ml                     125 ml            500 ml         4.2 *      Sodium lactate 11.2% should be diluted by a factor of 6 to reach a concentration of 0.16 M.

The use of larger dilution volumes (with a maximum of 100 ml of additional infusion fluid per 25 ml reconstituted Cardioxane) is usually recommended to increase the pH of the solution. Smaller dilution volumes (with a minimum of 25 ml of additional infusion fluid per 25 ml reconstituted Cardioxane) can be used if needed, based on the haemodynamic status of the patient.

Cardioxane is for single use only. Reconstituted and subsequently diluted product should be used immediately or within 4 hours if stored between 2°C and 8°C.

Parenteral drug products should be inspected visually for particulate matter whenever the solution and container permit. Cardioxane is normally a colourless to yellow solution immediately on reconstitution, but some variability in colour may be observed over time, which does not indicate loss of activity if the product has been stored as recommended. It is however recommended to dispose of the product if the colour immediately on reconstitution is not colourless to yellow.

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Adequate care and precautions should be taken in the disposal of items used to reconstitute and dilute Cardioxane.

7.   MANUFACTURER:
Cenexi - Laboratoires Thissen S.A., Braine-l'Alleud, Belgium