or injection vial. Swirl the contents of the vial until there are no visible particles in the resulting solution. The reconstituted solution will contain ISTODAX 5 mg/mL. The reconstituted ISTODAX solution is chemically stable for at least 8 hours at room temperature.
Extract the appropriate amount of ISTODAX from the vials to deliver the desired dose, using proper aseptic technique. Before intravenous infusion, further dilute ISTODAX in 500 mL 0.9% Sodium Chloride Injection, USP.
Infuse over 4 hours.
The diluted solution is compatible with polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyethylene (PE) infusion bags as well as glass bottles, and is chemically stable for at least 24 hours when stored at room temperature. However, it should be administered as soon after dilution as possible.
Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.
3 DOSAGE FORMS AND STRENGTHS
ISTODAX is supplied as a kit which includes a sterile, lyophilized powder in a single-use vial containing 10 mg of romidepsin and 20 mg of the bulking agent, povidone, USP. In addition, each kit includes 1 sterile vial containing 2 mL (deliverable volume) of the Diluent composed of 80% propylene glycol, USP, and 20% dehydrated alcohol, USP.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Monitoring: Laboratory Tests
Due to the risk of QT prolongation, potassium and magnesium should be within the normal range before administration of ISTODAX [See Warnings and Precautions (5.3) and Adverse Reactions (6)].
5.2 Hematologic
Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, these hematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary [See Dosage and Administration (2.2) and Adverse Reactions (6)].
5.3 Electrocardiographic Changes
Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [See Adverse Reactions (6)].
In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
5.4 Use in Pregnancy
There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action, ISTODAX may cause fetal harm when administered to a pregnant woman. A study in rats did not expose pregnant animals to enough romidepsin to fully eva luate adverse outcomes.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus [See Use in Specific Populations (8.1)].
5.5 Use in Women of Childbearing Potential
Advise women of childbearing potential that ISTODAX may reduce the effectiveness of estrogen-containing contraceptives. An in vitro binding assay determined that romidepsin competes with β-estradiol for binding to estrogen receptors [See Nonclinical Toxicology (13.1)].
6 ADVE |
