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