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AML 17
Stability and Storage
Information
Version 1: February 2009
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Clofarabine
Drug and Intravenous Formulation:
Clofarabine was initially formulated at a concentration of 1 mg/mL in
sodium chloride (9 mg/mL), United States Pharmacopeia (USP), and
Water for Injection, USP, quantity sufficient (qs) to 1 mL. Formulation
now released as above but in European Pharmacopeia (EP) normal saline.
Clofarabine is supplied in one vial size: a 20-mL clear, glass vial with gray
stopper and blue flip off seal. The 20-mL vial contains 20 mL (20 mg) of
solution with a pH range of 4.5 to 7.5. The solution is sterile, clear and
practically colourless, is preservative-free, and is free from foreign
matter.
Storage and Handling:
Vials containing undiluted clofarabine for injection should be stored at
25°C (77°F);
excursions permitted to 15-30°C (59-86°F). The current EU commercial
expiry period for clofarabine is 36 months at room temperature. Ongoing
stability studies will continue to confirm the appropriate quality of drug
product used for clinical trials beyond 24 months.
Clofarabine for injection should be diluted with 0.9% sodium chloride
injection USP or European Pharmacopeia (EP) normal saline (NS) or 5%
dextrose injection (D5W) USP or EP prior to IV infusion. If not used
immediately, in use storage times and conditions prior to use would not
normally be longer than 24 hours at 2-8oC unless dilution has taken place
under controlled and validated aseptic conditions
Intravenous Dosage and Administration:
Clofarabine should be diluted with NS or D5W prior to administration by
IV infusion. The dose should be administered by IV infusion over 1 to 2
hours daily for 5 consecutive days or as directed in a specific study
protocol. Treatment cycles are repeated every 2 to 6 weeks, depending
on the specific protocol. The dosage is based on the patient’s body
surface area (BSA), calculated using the actual height and weight before
the start of each cycle. Patients <1 year of age should be dosed based on
mg/kg as indicated in the specific protocol.
Dosages may be decreased according to criteria specified in the study
protocol.
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To prevent drug incompatibilities, no other medications should be
administered through the same IV line.
Individual dosages and schedules for haematological, solid tumour and
autoimmune studies will be specified within each of the study protocols.
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Mylotarg
Stability and Storage:
Prior to Reconstitution: Mylotarg should be stored refrigerated 2° to 8°
C (36° to 46° F) and protected from light.
After Reconstitution: Follow the instructions for reconstitution, dilution,
and administration in the section above. See Table 11 below for
reconstitution, dilution, and administration storage conditions and time
intervals.
TABLE 11: STORAGE CONDITION AND TIME FOR RECONSTITUTION,
DILUTION, AND ADMINISTRATION
The following time intervals for reconstitution, dilution, and administration should
be followed for storage of the reconstituted solution
Time Intervals
Total Maximum
Hours a
Reconstitution
Dilution
Administration
≤ 2 hours at room
temperature
or refrigeration
≤ 16 hours at room
temperature
2 hour infusion
20
a: Total maximum time allowed for the storage of the reconstituted and diluted
solutions and completion of infusion.
Instructions for Use, Handling and for Disposal:
Mylotarg should be inspected visually for particulate matter and
discoloration, once in the transfer syringe. Additionally, the diluted
admixture solution should be inspected visually for particulate matter and
discoloration. Protect from light and use an UV protective bag over the
IV bag during infusion. Vials are for single use.
Aseptic technique must be strictly observed throughout the handling of
Mylotarg since no bacteriostatic agent or preservative is present.
Institutional procedures for handling and disposal of anticancer drugs
should be used. Several guidelines on this subject have been published.1,2,3
How supplied:
MylotargR (gemtuzumab ozogamicin for Injection) is supplied as a singlevial package with an amber glass vial containing 5 mg of Mylotarg
lyophilized powder. Single-unit 5 mg package: each vial contains 5 mg of
Mylotarg. NDC 0008-4510-01.
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Arsenic Trioxide
Drug and Chemical Formula:
Trisenox is a sterile injectable solution of arsenic trioxide. The molecular
formula of the drug substance in the solid state is As2O3, with a
molecular weight of 197.8.
Physical and Chemical Information:
Trisenox is formulated as a sterile, nonpyrogenic, clear solution of arsenic
trioxide in Water-for-Injection using sodium hydroxide and dilute
hydrochloric acid to adjust to pH8. The drug product is preservativefree. Arsenic trioxide, the active ingredient, is present at a
concentration of 1 mg/mL. Inactive ingredients and their respective
approximate concentrations are sodium hydroxide (1.2 mg/mL) and
hydrochloric acid, which is used to adjust the pH.
Drug Product, Storage and Handling:
Trisenox is supplied as a sterile, clear, colorless solution in 10 mL clear
glass, single-use ampules containing 10 mg of arsenic trioxide.
Trisenox should be stored at 25°C (77°F). Stability studies show that
Trisenox is stable for at least 3 years at 25°C. Excursions are permitted
to 15 to 30°C (59 to 86°F). Do not freeze ampules.
Trisenox drug product should be withdrawn from the ampule immediately
before it is
diluted with 100 to 250 mL 5% dextrose injection, USP, or 0.9% Sodium
Chloride for
Injection, USP, using aseptic technique. The ampule is single-use and does
not contain any preservatives. Unused portions of each ampule should be
discarded properly, and unused portions should not be saved for later
dilution and administration.
Trisenox injection is stable when stored for up to 14 days in intravenous
(IV) bags
containing 5% Dextrose Injection, USP or 0.9% Sodium Chloride
Injection, USP. No
significant changes in the chemical and physical properties of Trisenox
were observed in a study conducted to determine whether the drug, when
diluted in 5% dextrose injection or 0.9% sodium chloride injection,
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changed significantly after being stored 5, 7, or 14 days at refrigerator
or ambient temperature.
Trisenox should not be mixed with any other medications.
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CEP 701
Description of Drug Substance and Formulations:
CEP-701 drug substance is a chemically synthesized derivative of K-252a.
K-252a is the fermentation product of N. longicatena and belongs to a
class of compounds identified as indolocarbazole alkaloids.
CEP-701 drug substance is a white to yellow solid that has a molecular
weight of 439.47 g/mol. CEP-701 drug substance is stable when stored at
20 C to 25 Cand protected from light.
CEP-701 drug product is supplied as a solution in a carrier of polysorbate
80 NF and propylene glycol USP, with a 25 mg/mL CEP-701 concentration.
The drug product may be packaged in either 20-mL amber glass vials, or
in amber glass bottles (50 or 100 mL fill). The formulation, packaged in
the amber glass bottles also contains butylated hydroxyanisole as an
antioxidant. A placebo drug product may be supplied as a solution of
polysorbate 80 NF and propylene glycol USP, with FD&C Yellow #5.
Storage and Handling:
CEP-701 drug product should be stored at controlled room temperature
of 20 C to 25 C (68 F to 77 F), and protected from light.
Prior to oral administration, the drug product solution is diluted with
juice at a ratio of
1:20. The drug product is compatible with apple, pineapple, grape juices
(100% juices), V8 100% vegetable juice, cranberry juice, and orange juice.
Once study drug is dispensed into juice it normally should be consumed
immediately. If solutions of study drug in juice need to be stored, one
hour at room temperature (20° to 25° C, or for centres outside the U.S.,
below 25°C), or up to 8 hours refrigerated (2°C to 8°C) is
recommended. CEP-701 should be protected from light.
The stability of the drug substance and drug product continues to be
monitored.
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Everolimus
Formulation:
All formulations are based on a RAD001 solid dispersion intermediate
that was selected on the basis of the chemical stability of the active
ingredient and properties allowing for a good in vivo performance.
Dosage forms:
Tablets: 2.5 mg, 5 mg and 10 mg
Composition/excipients:
Tablets: butylhyroxytoluene/butylated hydroxytoluene (BHT), magnesium
stearate, lactose monohydrate, hypromellose/hydroxypropyl
methylcellulose, crospovidone, lactose anhydrous. The excipients comply
with the requirements of the applicable compendial monographs (Ph. Eur.,
USP/NF).
Stability:
Current stability data permit a shelf life of either 36 months (for 5 mg
tablet variants based on solid dispersion dried by evaporation/drying
oven) or 24 months (for 2.5 mg, 5 mg and 10 mg tablet variants based on
solid dispersion dried by paddle dryer), assuming correct storage below
30°C in the original double sided aluminium blister and protected from
light and moisture.
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