Alimta® (pemetrexed): Storage and Stability of Reconstituted Vials

Diluent

Reconstitution and further dilution prior to IV infusion are only recommended with 0.9% sodium chloride injection (preservative free), USP. Pemetrexed is physically incompatible with diluents containing calcium such as Lactated Ringer’s injection, USP and Ringer’s injection, USP. Coadministration of pemetrexed with other drugs and diluents has not been studied, and therefore is not recommended.^1,2

Storage and Stability After Reconstitution or Dilution

Label Recommendations: Refrigerated Storage

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 2°C to 8°C.¹

Discard any unused portion. Pemetrexed is not light sensitive.²

Guidance on Room Temperature Storage

Where reconstituted solutions of pemetrexed cannot be stored under refrigerated conditions for a certain period, Lilly advises customers to follow the USP guidance for low-risk compounded sterile preparations, prepared under aseptic technique (ISO Class 5 or cleaner air), which allows for the storing of reconstituted solutions such as pemetrexed at controlled room temperature for up to 6 hours in the vial and 12 hours in the infusion solution (for a total of 18 hours).^2,3

Stability in Polypropylene Syringes

Although a stability study demonstrated that pemetrexed solutions were physically and chemically stable when stored in polypropylene syringes at room temperature for 2 days and when refrigerated for 31 days, this study did not address bacteriologic concerns.⁴ Therefore, storage should be limited to the manufacturer-recommended 24 hours under refrigeration.¹

Stability in PVC Bags for >24 Hours

Although chemical stability is unaffected, a substantial amount of microparticulates may form if pemetrexed diluted in infusion solutions is stored under refrigeration in PVC bags for longer than 24 hours.⁵ Therefore, storage should be limited to the manufacturer-recommended 24 hours under refrigeration.¹

Physical Instability of Frozen Solutions in PVC Bags

Although chemically stable, freezing of pemetrexed admixtures in PVC bags should be avoided due to the large number of microparticulates formed. Therefore, previously frozen pemetrexed solutions should not be used.⁶

References

1. Alimta [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. The United States Pharmacopeial (USP) Convention, Inc. U.S. Pharmacopeia 43 and National Formulary 38 2S. Rockville, MD: United States Pharmacopeia Convention, Inc; 2020. http://www.usp.org/usp-nf

4. Zhang Y, Trissel LA. Physical and chemical stability of pemetrexed solutions in plastic syringes. Ann Pharmacother. 2005;39(12):2026-2028. http://dx.doi.org/10.1345/aph.1G161

5. Zhang Y, Trissel LA. Physical and chemical stability of pemetrexed in infusion solutions. Ann Pharmacother. 2006;40(6):1082-1085. http://dx.doi.org/10.1345/aph.1G715

6. Zhang Y, Trissel LA. Physical instability of frozen pemetrexed solutions in PVC bags. Ann Pharmacother. 2006;40(7-8):1289-1292. http://dx.doi.org/10.1345/aph.1G558

Glossary

ISO = International Organization for Standardization

IV = intravenous

Lilly = Eli Lilly and Company

PVC = polyvinyl chloride

USP = United States Pharmacopeia