pemetrexed: package leaflet

intravenous infusion administration.

pemetrexed to facilitate delivery of the label amount.

Reconstitute each 100 mg vial with 4.2 ml of 9 mg/ml (0.9%) sodium chloride solution for injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed.

ALIMTA 500 mg:
Reconstitute each 500 mg vial with 20 ml of 9 mg/ml (0.9%) sodium chloride 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.

with 9 mg/ml (0.9 %) sodium chloride solution for injection, without preservative, and administered as an intravenous infusion over 10 minutes.

chloride and polyolefin lined administration sets and infusion bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer’s Injection and Ringer’s Injection.

discolouration prior to administration. If particulate matter is observed, do not administer.

7.
Pemetrexed solutions are for single use only. Any unused product or waste material should 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 a 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.

without preservative. The appropriate volume of pemetrexed concentrate must be diluted to 100 ml with 5% glucose solution or 0.9% sodium chloride solution and administered as an intravenous infusion over 10 minutes.

chloride and polyolefin lined administration sets and infusion bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer’s Injection and Ringer’s Injection.

Armisarte contains trometamol as an excipient. Trometamol is incompatible with cisplatin resulting in degradation of cisplatin. This medicinal product must not be mixed with other medicinal products. Intravenous lines should be flushed after administration of Armisarte.

discolouration prior to administration. If particulate matter is observed, do not administer.

two times. Any unused medicinal product left in the vial, which has exceeded the in-use shelf life, or waste material should 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 a 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.

Diluted solution

Chemical and physical in-use stability of infusion solution of pemetrexed was demonstrated for 24 hours at room temperature and 7 days 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 normally not be longer than 24 hours at 2 °C-8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS
OF THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for pemetrexed, the scientific conclusions of PRAC are as follows:

In view of available data on the pharmacokinetics of pemetrexed and considering in vitro studies indicated that pemetrexed is actively secreted by organic anion transporter 3 (OAT3) and IC50 values for proton pump inhibitors, the PRAC considers a drug-drug interaction between proton pump inhibitors and pemetrexed is at least a reasonable possibility. The PRAC concluded that the product information of products containing pemetrexed should be amended accordingly.

Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for pemetrexed the CHMP is of the opinion that the benefit- risk balance of the medicinal product(s) containing pemetrexed is unchanged subject to the proposed changes to the product information.

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.