AML 17
Stability and Storage Information
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, quantitysufficient (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 withgray stopper and blue flip off seal. The 20-mL vial contains 20 mL (20 mg) of solution witha pH range of 4.5 to 7.5. The solution is sterile, clear and practically colourless, ispreservative-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 forclofarabine is 36 months at room temperature. Ongoing stability studies will continue toconfirm 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 orEuropean Pharmacopeia (EP) normal saline (NS) or 5% dextrose injection (D5W) USP or EPprior to IV infusion. If not used immediately, in use storage times and conditions prior to usewould not normally be longer than 24 hours at 2-8oC unless dilution has taken place undercontrolled and validated aseptic conditions
Intravenous Dosage and Administration:
Clofarabine should be diluted with NS or D5W prior to administration by IV infusion. Thedose should be administered by IV infusion over 1 to 2 hours daily for 5 consecutive days oras 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. Patients1 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.
To prevent drug incompatibilities, no other medications should be administered through thesame IV line.
Individual dosages and schedules for haematological, solid tumour and autoimmune studieswill be specified within each of the study protocols.
Mylotarg
Stability and Storage:
Prior to Reconstitution: Mylotarg should be stored refrigerated 2° to 8° C (36° to 46° F) andprotected from light.
After Reconstitution: Follow the instructions for reconstitution, dilution, and administration inthe section above. See Table 11 below for reconstitution, dilution, and administration storageconditions and time intervals.
TABLE 11: STORAGE CONDITION AND TIME FOR RECONSTITUTION, DILUTION, ANDADMINISTRATION
The following time intervals for reconstitution, dilution, and administration should be followed for storage of the reconstituted solutionTime 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 andcompletion of infusion.
Instructions for Use, Handling and for Disposal:
Mylotarg should be inspected visually forparticulate matter and discoloration, once in the transfer syringe. Additionally, the diluted
admixture solution should be inspected visually for particulate matter and discoloration. Protectfrom 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 nobacteriostatic agent or preservative is present. Institutional procedures for handling and disposalof 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 single-vial package with anamber 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.
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 inWater-for-Injection using sodium hydroxide and dilute hydrochloric acid to adjust to pH8. The drug product is preservative-free. 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, changed significantly after being stored 5, 7, or 14 days at refrigerator or ambient temperature.
Trisenox should not be mixed with any other medications.
CEP 701
Description of Drug Substance and Formulations:
CEP-701 drug substance is a chemically synthesized derivative of K-252a. K-252a is thefermentation product of N. longicatena and belongs to a class of compounds identified asindolocarbazole alkaloids.
CEP-701 drug substance is a white to yellow solid that has amolecular weight of 439.47 g/mol. CEP-701 drug substance is stable when stored at20C to 25Cand protected from light.
CEP-701 drug product is supplied as a solution in a carrier of polysorbate 80 NF andpropylene glycol USP, with a 25 mg/mL CEP-701 concentration. The drug product maybe packaged in either 20-mL amber glass vials, or in amber glass bottles (50 or 100 mLfill). The formulation, packaged in the amber glass bottles also contains butylatedhydroxyanisole as an antioxidant. A placebo drug product may be supplied as a solutionof 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 20C to 25C(68F to 77F), 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 isdispensed into juice it normally should be consumed immediately. If solutions of studydrug 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.
Everolimus
Formulation:
All formulations are based on a RAD001 solid dispersion intermediate thatwas selected on the basis of the chemical stability of the active ingredientand 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 compendialmonographs (Ph. Eur., USP/NF).
Stability:
Current stability data permit a shelf life of either 36 months (for 5 mg tabletvariants based on solid dispersion dried by evaporation/drying oven) or 24months (for 2.5 mg, 5 mg and 10 mg tablet variants based on soliddispersion dried by paddle dryer), assuming correct storage below 30°C inthe original double sided aluminium blister and protected from light andmoisture.
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