ROMIDEPSIN Drug Interactions: What You Need to Know

INTERACTIONS Carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered romidepsin and warfarin or coumarin derivatives ( 7.1 ). Monitor for toxicities related to increased romidepsin exposure when co- administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ).

7.1 Warfarin or Coumarin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving romidepsin concomitantly with warfarin. Monitor PT and INR more frequently in patients concurrently receiving romidepsin and warfarin <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>.

7.2 Drugs That Inhibit CYP3A4 Enzymes Strong CYP3A4 inhibitors increase concentrations of romidepsin <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span> when romidepsin is initially co-administered with strong CYP3A4 inhibitors.

7.3 Drugs That Induce CYP3A4 Enzymes Rifampin (a potent CYP3A4 inducer) increased the concentrations of romidepsin <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . Avoid co-administration of romidepsin with rifampin. The use of other potent CYP3A4 inducers should be avoided when possible.

None. None ( 4 ).

AND PRECAUTIONS Myelosuppression: romidepsin can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts during treatment with romidepsin; interrupt and/or modify the dose as necessary ( 5.1 ). Infections: Fatal and serious infections. Reactivation of DNA viruses (Epstein Barr and hepatitis B). Consider monitoring and prophylaxis in patients with evidence of prior hepatitis B ( 5.2 ). Electrocardiographic (ECG) changes: Consider cardiovascular monitoring in patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking medicinal products that lead to significant QT prolongation. Ensure that potassium and magnesium are within the normal range before administration of romidepsin ( 5.3 ). Tumor lysis syndrome: Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and appropriate precautions taken ( 5.4 ). Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception ( 5.5 , 8.1 , 8.3 ).

5.1 Myelosuppression Treatment with Romidepsin can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia. Monitor blood counts regularly during treatment with romidepsin and modify the dose as necessary <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 ) and Adverse Reactions ( 6.1 )]</span>.

5.2 Infections Fatal and serious infections have been reported in clinical trials of romidepsin, including pneumonia, sepsis, and viral reactivation, including reactivation of Epstein Barr and hepatitis B viruses. These infections can occur during and following treatment. The risk of life-threatening infections may be greater in patients with a history of prior treatment with monoclonal antibodies directed against lymphocyte antigens and in patients with disease involvement of the bone marrow <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . Reactivation of hepatitis B virus infection was reported in 1% of patients in clinical trials. In patients with evidence of prior hepatitis B infection, consider monitoring for reactivation, and consider antiviral prophylaxis. Reactivation of Epstein Barr viral infection leading to liver failure has occurred in recipients of romidepsin including after ganciclovir prophylaxis.

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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. 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, consider cardiovascular monitoring of ECGs at baseline and periodically during treatment. Confirm that potassium and magnesium levels are within normal range before administration of romidepsin <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

5.4 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) has been reported to occur in recipients of romidepsin, including in 1% of patients with tumor stage CTCL. Patients with advanced stage disease and/or high tumor burden are at greater risk, should be closely monitored, and managed as appropriate.

5.5 Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal studies, romidepsin can cause fetal harm when administered to a pregnant woman. In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes at exposures below those in patients at the recommended dose of 14 mg/m 2 . Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )]</span> .