Pharmaceutical particulars : מידע רוקחי

6     PHARMACEUTICAL PARTICULARS
6.1     List of excipients
Polyoxyl Castor Oil
(Macrogol glycerol ricinolate)
Ethanol anhydrous
Nitrogen

6.2     Incompatibilities
Polyoxyl castor oil (macrogol glycerol ricinolate) can result in DEHP [di-(2- ethylhexyl)phthalate] leaching from plasticised polyvinyl chloride (PVC) containers, at levels which increase with time and concentration. Consequently, the preparation, storage and administration of diluted paclitaxel concentrate should be carried out using non-PVC-containing equipment.


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

After first opening
Use within 28 days of first opening

After dilution with infusion solutions
The maximum storage times for infusion solutions with Ebetaxel in glucose 5% respectively sodium chloride 0.9% are 14 days when stored in a refrigerator at 5±3oC.
The maximum storage times for Ebetaxel infusion solutions prepared in glucose 5% are 1 week when stored at room temperature without light protection.The maximum storage times for Ebetaxel infusion solutions prepared in sodium chloride 0.9% are 5 days when stored at room temperature without light protection.


Infusion solution after dilution:
From a microbiological point of view, the ready to use preparation should be used immediately.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Diluted solution should be for single use only.

6.4     Special precautions for storage

Store below 25°C. Store
 vials in the original

 packaging in order to
 protect the content from
light
6.5     Nature and contents of container


Colourless Type I glass vial with grey fluropolymer-coated halobutyl rubber stoppers and aluminium overseal.


Packs of 1 vial containing 5ml, 16.7ml, 25ml, 50ml, and 100ml of Paclitaxel 6mg/ml Concentrate for Solution for Infusion.



6.6     Special precautions for disposal
Handling: as with all antineoplastic agents, caution should be exercised when handling Paclitaxel 6mg/ml Concentrate for Solution for Infusion. Dilution should be carried out under aseptic conditions by trained personnel in a designated area.
Adequate protective gloves should be worn. Precautions should be taken to avoid contact with the skin and mucous membranes. In the event of contact with the skin, the area should be washed with soap and water. Following topical exposure, tingling, burning and redness have been observed. In the event of contact with the mucous membranes, these should be flushed thoroughly with water. Upon inhalation, dyspnoea, chest pain, burning throat and nausea have been reported.


If unopened vials are refrigerated, a precipitate may form that redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded.


Preparation for IV administration: Prior to infusion, Paclitaxel 6mg/ml Concentrate for Solution for Infusion must be diluted, using aseptic techniques, in 0.9% sodium chloride injection, or 5% glucose injection, or 5% glucose and 0.9% sodium chloride injection, to a final concentration of 0.3 to 1.2 mg/mL.


Upon preparation, solutions may show haziness, which is attributed to the formulation vehicle, and is not removed by filtration. Paclitaxel infusion should be administered through an in-line filter with a microporous membrane ≤0.22μm. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line filter.


There have been rare reports of precipitation during paclitaxel infusions, usually towards the end of a 24 hour infusion period. Although the cause of this precipitation has not been elucidated, it is probably linked to the supersaturation of the diluted solution. To reduce the precipitation risk, paclitaxel should be used as soon as possible after dilution and excessive agitation, vibration or shaking should be avoided. The infusion sets should be flushed thoroughly before use. During infusion the appearance of the solution should be inspected regularly and the infusion should be stopped if precipitation is present.


To minimise patient exposure to DEHP, which may be leached from plasticised PVC infusion bags, sets, or other medical instruments, diluted paclitaxel solutions should be stored in non-PVC bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets. Use of filter devices (eg. IVEX-2®) which incorporate short inlet and/or outlet plasticised PVC tubing has not resulted in significant leaching of DEHP.


Disposal: All items used for preparation, administration or otherwise coming into contact with paclitaxel injection should undergo disposal according to local guidelines for the handling of cytotoxic compounds.