Pharmaceutical particulars : מידע רוקחי

6. Pharmaceutical particulars

6.1 List of excipients
None.

6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life
Unopened vial
The expiry date of the product is indicated on the packaging material.
Reconstituted solutions
Chemical and physical in-use stability has been demonstrated for 12 hours at 30°C.
From a microbiological point of view, unless the method of reconstitution precludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage
Store below 250C.

Reconstituted solution:
Do not store the reconstituted product in a refrigerator (2 - 8°C) as this might cause precipitation. Solutions showing any sign of precipitation should not be used.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container
100ml Type-I clear moulded lyo glass vial with a 20 mm bromobutyl rubber stopper sealed with a 20 mm flip-off seal. Vials may or may not be sleeved with plastic shrink sleeve/bottom (puck). This plastic sleeving is not in contact with the drug product and is there to provide additional protection during transportation. This improves the safe handling of the medicinal product by both healthcare professionals and pharmaceutical personnel.

TREOSULFAN RAZ 5g is available in packs of 1 or 5 vials.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling
Treosulfan is used for intravenous infusion after being dissolved in 100 mL of water for injections.
The reconstituted solution is a clear, colourless solution.
Inspect visually prior to use. Only clear solutions without particles should be used.
Any reconstituted solution that shows evidence of precipitation should not be used and should be destroyed with regard to legal requirements for disposal of hazardous waste (see below).
For single use only, discard any unused contents.
As with all cytotoxic substances, appropriate precautions should be taken when handling Treosulfan.
Guidelines for the safe handling of antineoplastic agents:
1. Trained personnel should reconstitute the medicinal product.
2. This should be performed in a designated area.
3. Adequate protective gloves, masks and clothing should be worn.
4. Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. In case the solution comes in contact with the skin or the eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of the skin. Medical advice should be sought if the eyes are affected.
5. Cytotoxic preparations should not be handled by staff who may be pregnant.
6. Adequate care and precautions should be taken in the disposal of items (syringes, needles, etc.) used to reconstitute cytotoxic drugs.
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 reduced by the use of a venting needle.

Treosulfan has mutagenic and carcinogenic potential. Remnants of the medicinal product as well as all materials that have been used for reconstitution and administration must be destroyed according to standard procedures applicable to antineoplastic agents, with due regard to current laws related to the disposal of hazardous waste.
Instructions for reconstitution of Treosulfan
To avoid solubility problems during reconstitution the following aspects should be regarded.
1. The solvent, water for injections, is warmed to 25 - 30°C (not higher!) by using a water bath.
2. The Treosulfan is carefully removed from the inner surface of the infusion bottle by shaking.
This procedure is very important, because moistening of powder that sticks to the surface results in caking. In case caking occurs the bottle has to be shaken long and vigorously.
3. One side of the double-sided cannula is put into the rubber stopper of the water bottle. The Treosulfan bottle is then put on
the other end of the cannula with the bottom on top. The whole construction is converted and the water let run into the lower bottle while the bottle is shaken gently.
Following these instructions, the whole reconstitution procedure should take no longer than 2 minutes.