Istodax

/ Neopharm Scientific

The recommended dose of romidepsin is 14 mg/m² administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the drug.
See prescribing information for full details.

-Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
-Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.

Hypersensitivity to the active substance or to any of the excipients.

Myelosuppression:
This treatment can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia. Monitor blood counts regularly during treatment and modify the dose as necessary.
Infections:
Fatal and serious infections, including pneumonia, sepsis, and viral reactivation, including Epstein Barr and hepatitis B viruses, have been reported in clinical trials. These can occur during treatment and within 30 days after 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.
Reactivation of hepatitis B virus infection has occurred in 1% of PTCL patients in clinical trials in Western populations. 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 a trial of patients with relapsed or refractory extranodal NK/T-cell lymphoma. In one case, ganciclovir prophylaxis failed to prevent Epstein Barr viral reactivation.
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.
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.
Tumor Lysis Syndrome:
Tumor lysis syndrome (TLS) has been reported to occur in 1% of patients with tumor stage CTCL and 2% of patients with Stage III/IV PTCL. Patients with advanced stage disease and/or high tumor burden are at greater risk, should be closely monitored, and managed as appropriate.
Embryo-Fetal Toxicity:
Based on its mechanism of action and findings from animal studies, this drug 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/m². Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Advise males with female sexual partners of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose.

The most frequent adverse reactions are:
Nausea, Asthenia/Fatigue, Infections,Vomiting, Anorexia, Hypomagnesemia, Diarrhea, Pyrexia, Anemia, Thrombocytopenia, Dysgeusia
Constipation, Neutropenia, pruritus, hypotension.
See prescribing information for full details.

Warfarin or Coumarin Derivatives:
Prolongation of PT and elevation of INR were observed in a patient receiving this drug concomitantly with warfarin. Monitor PT and INR more frequently.
Drugs That Inhibit CYP3A4 Enzymes:
Strong CYP3A4 inhibitors increase concentrations of romidepsin. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity.
Drugs That Induce CYP3A4 Enzymes:
Rifampin (a potent CYP3A4 inducer) increased the concentrations of romidepsin Avoid co-administration of this drug with rifampin.
The use of other potent CYP3A4 inducers should be avoided when possible.

Pregnancy:
Based on its mechanism of action and findings from animal studies, this medicinal product can cause embryo-fetal harm when administered to a pregnant woman.
There are no available data on use in pregnant women to inform a drug associated risk of major birth defects and miscarriage. In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes including embryo-fetal toxicity and malformations at exposures below those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus and to avoid becoming pregnant while receiving this drug, and for at least 1 month after the last dose.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
Lactation:
There are no data on the presence of romidepsin or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the breastfed child, advise lactating women not to breastfeed during treatment and for at least 1 week after the last dose.

No specific information is available on the treatment of overdosage of romidepsin.
Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2-fold the recommended human dose based on the body surface area, included irregular respiration, irregular heartbeat, staggering gait, tremor, and tonic convulsions.
In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for romidepsin and it is not known if romidepsin is dialyzable.

This is a cytotoxic drug. Follow applicable special handling and disposal procedures.