Pharmaceutical particulars : מידע רוקחי

 6        PHARMACEUTICAL PARTICULARS

6.1      List of excipients

Powder
No excipients.
Solvent
Ethanol, anhydrous.


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 and dilution
The solution should be administered within 3 hours after reconstitution and dilution of the product, at temperatures below 20-22°C.
The solution should be protected from light until end of administration.


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.
The lyophilisate can appear as a fine powder, however handling can cause it to appear as a more heavy and lumpy lyophilisate than as a powdery lyophilisate due to the mechanical instability of the freeze drying cake. The presence of an oily film can be an indication of melting of the medicinal product.
Such products are not accepted for use due to the risk of temperature excursions to more than 30°C. This medicinal product 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.


6.5    Nature and contents of container

Powder: Brown type I hydrolytic glass vial (50 ml) with light grey 20 mm bromobutyl rubber stopper and sealed with a dark red aluminium flip-off cap.

Solvent: Type I glass ampule (5 ml).

6.6    Special precautions for disposal

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

Preparation of intravenous solution:
Dissolve Carmustine (100 mg powder) with 3 ml of the supplied sterile refrigerated Ethanol solvent in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol before sterile water for injections is added. 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

Reconstitution as recommended results in a clear colourless to light yellow stock solution which has to be further diluted to 500 ml sodium chloride 9 mg/ml (0.9%) for injection, or 5% glucose for injection in glass containers. The 530 ml diluted solution (i.e. the ready-to- use solution) should be mixed for at least 10 seconds before administration. The Ready-to- Use solution must be given intravenously and should be administered by I.V. drip over 1-2 hour period and administration should be finalised within 3 hours from reconstitution of the product. Injection of Carmustine over shorter periods of time may produce intense pain and burning at the site of injection.

Administration of the infusion should be performed using a PVC free PE infusion set.
During administration of the medicinal product, the container shall be of suitable glass ware. Further, the ready-to-use solution solution needs to be protected from light (e.g.
using alu-foil wrapped around the container of the ready-to-use solution) and preferably kept at temperatures below 20-22°C as carmustine degrades faster at higher temperatures.

NOTE: Reconstituted vials stored under refrigeration should be examined for crystal formation prior to use. If crystals are observed, they may be redissolved by warmingthe 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 andappear 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 copiousamount 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 wastemay be flushed with copious amounts of water.
7.   The work surface should be covered with disposable plastic-backedabsorbent 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 accordancewith local requirements for biohazardous waste.