Pharmaceutical particulars : מידע רוקחי

6       PHARMACEUTICAL PARTICULARS

6.1     List of excipients
Dehydrated Alcohol.


6.2     Incompatibilities

Compatibility/ Incompatibility with Containers
The intravenous solution is unstable in polyvinyl chloride container. The carmustine solution can be administered from the glass bottles or polypropylene container only.
The pharmaceutical medicine should be used based on the instructions in Section 6.6 and not mixed up with other pharmaceutical medicines.


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

After reconstitution as recommended, Carmustine is stable for 24 hours under refrigeration (2°C - 8°C) in glass container. Protect from light.


The reconstituted solution further diluted with 500 ml sodium chloride for injection or 5% glucose for injection, in glass or polypropylene containers, results in a solution which should be utilized within 4 hours at room temperature and be protected from light. These solutions are also stable for 24 hours under refrigeration (2-8°C) and an additional 6 hours at room temperature protected from light.
Taking into consideration the microbial aspect, it is advised to be used immediately after dilution.


6.4     Special precautions for storage
Store in a refrigerator (20C–80C).
The original package should be protected from light.
The dry frozen product does not contain any preservatives and is suitable only for one use.
There can be physical appearances of sharp flakes in the unopened vial as far as rigid mass, however without any decomposition of carmustine. The storage of carmustine at 27°C or higher temperature can lead to liquefaction of the substance, since carmustine has a low melting point (ca. 30.5°C to 32.0°C).

An indication of the decomposition is the appearance of an oil film at the bottom of the vial. This medicine should not be used any further. When you are not clear about the fact whether the product is adequately cooled, then you should immediately inspect each and every vial in the carton. For verification, hold the vial in bright light.
Carmustine appears with small quantities of dried flakes or dried rigid mass.


6.5    Nature and contents of container
Powder: Type I amber glass vial (30 ml) sealed with a dark grey bromobutyl lyo rubber stopper and aluminium seal having polypropylene cap.

Diluent: Type I glass vial (5 ml) sealed with a grey bromobutyl rubber stopper with an aluminium seal having polypropylene cap.


6.6    Special precautions for disposal

IMPORTANT NOTE: The lyophilized dosage formulation contains no preservative and is not intended as multiple dose vial. Reconstitution and further dilutions should be carried out under aseptic conditions.

Preparation of intravenous solution:
Dissolve Carmustine with 3 ml of the supplied sterile diluent and then aseptically add 27 ml of sterile water for injection to the alcohol solution. Each ml of resulting solution will contain 3.3 mg of Carmustine in 10% ethanol and has a pH of 5.6 to 6.0.

Reconstitution as recommended results in a clear colourless to yellow solution which has to be further diluted to 500 ml sodium chloride for injection, or 5% glucose for injection. The reconstituted solution must be given intravenously and should be administered by I.V. drip over one to two hour period. Injection of Carmustine over shorter periods of time may produce intense pain and burning at the site of injection.


NOTE: Reconstituted vials stored under refrigeration should be examined for crystal formation prior to use. If crystals are observed, they may be redissolved by warming the vial to room temperature with agitation.

Carmustine has a low melting point (approximately 30.5-32.0oC or 86.9-89.6oF).
Exposure of this drug to this temperature or above will cause the drug to liquefy and appear as an oil film in the bottom of the vials. This is a sign of decomposition and vials should be discarded.
Guidelines for the safe handling of the antineoplastic agents:
1. Trained personnel should reconstitute the drug.
2. This should be performed in a designated area.
3. Adequate protective gloves should be worn.
4. Precautions should be taken to avoid the drug accidentally coming into contact with eyes. In the event of contact with the eyes, flush with copious amount of water and/or saline.
5. The cytotoxic preparation should not be handled by pregnant staff.
6. Adequate care and precaution should be taken in the disposal of items (syringes, needles etc.) used to reconstitute cytotoxic drugs. Excess material and body waste may be disposed of by placing in double sealed polythene bags and incinerating at a temperature of 1,000oC. Liquid waste may be flushed with copious amounts of water.
7. The work surface should be covered with disposable plastic-backed absorbent paper.
8. Use Luer-Lock fittings on all syringes and sets. Large bore needles are recommended to minimise pressure and the possible formation of aerosols.
The latter may also be reduce by the use of a venting needle.
9. Any unused product or waste material should be disposed of in accordance with local requirements for biohazardous waste.