n a patient receiving ISTODAX concomitantly with warfarin. Although the interaction potential between ISTODAX and Coumadin or Coumadin derivatives has not been formally studied, physicians should carefully monitor PT and INR in patients concurrently administered ISTODAX and Coumadin or Coumadin derivatives [See Clinical Pharmacology (12.3)].
7.2 Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes
Romidepsin is metabolized by CYP3A4. Although there are no formal drug interaction studies for ISTODAX, strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase concentrations of romidepsin. Therefore, co-administration with strong CYP3A4 inhibitors should be avoided if possible. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.
Co-administration of potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital) may decrease concentrations of romidepsin and should be avoided if possible. Patients should also refrain from taking St. John's Wort.
7.3 Drugs that Inhibit Drug Transport Systems
Romidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If ISTODAX is administered with drugs that inhibit P-gp, increased concentrations of romidepsin are likely, and caution should be exercised.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D [See 'Warnings and Precautions' section].
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 developmental 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 harm to the fetus.
In an animal reproductive study, pregnant rats received daily intravenous romidepsin during the period of organogenesis up to a dose of 0.06 mg/kg/day (0.36 mg/m2/day). This dose in rats is approximately equivalent to 18% the estimated human daily dose based on body surface area and resulted in 5% reduction in fetal weight. Embryofetal toxicities associated with the use of ISTODAX were not adequately assessed in this study.
8.3 Nursing Mothers
It is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and effectiveness of ISTODAX in pediatric patients has not been established.
8.5 Geriatric Use
Of the 167 patients with CTCL in trials, 23% were >65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out.
8.6 Hepatic Impairment
No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter
pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with mode |
