Pharmaceutical particulars : מידע רוקחי

6.     PHARMACEUTICAL PARTICULARS
6.1     List of excipients

Mannitol
Hydrochloric acid
Sodium hydroxide
Water for injection
Nitrogen

6.2     Incompatibilities

Pemetrexed is physically incompatible with diluents containing calcium, including lactated Ringer’s injection and Ringer’s injection. In the absence of other 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 materials.

Reconstituted and infusion solutions
When prepared as directed, reconstituted and infusion solutions of PEMETREXED contain no antimicrobial preservatives.
Chemical and physical in-use stability of reconstituted and infusion solutions of pemetrexed were demonstrated for 24 hours at refrigerated temperature.
From a microbiological point of view, the product 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 not be longer than 24 hours at 2oC to 8oC.



6.4 Special precautions for storage

Unopened vial
Do not store above 25°C
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5        Nature and contents of container

Type I glass vial with rubber stopper containing 500 mg of pemetrexed. Pack of 1 vial.

6.6        Special precautions for disposal and other handling

1.      Use aseptic technique during the reconstitution and further dilution of pemetrexed for intravenous infusion administration.

2.      Calculate the dose and the number of PEMETREXED S.K. vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of label amount.

3.      Reconstitute 500 mg vials with 20 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed.
Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in colour from colourless to yellow or green-yellow without adversely affecting product quality. The pH of the reconstituted solution is between 6.6 and 7.8.
Further dilution is required.

4.      The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with sodium chloride 9 mg/ml (0.9 %) solution for injection, without preservative, and administered as an intravenous infusion over 10 minutes.

5.      Pemetrexed infusion solutions prepared as directed above are compatible with polyvinyl chloride and polyolefin lined administration sets and infusion bags.

6.      Parenteral medicinal products must be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.

7.      Pemetrexed solutions are for single use only. Any unused medicinal product or waste material must be disposed of in accordance with local requirements.

Preparation and administration precautions: As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended. If a pemetrexed solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If pemetrexed solutions contact the mucous membranes, flush thoroughly with water. Pemetrexed is not a vesicant.
There is not a specific antidote for extravasation of pemetrexed. There have been few reported cases of pemetrexed extravasation, which were not assessed as serious by the investigator. Extravasation should be managed by local standard practice as with other non- vesicants.