romidepsin (Rx)

Brand and Other Names:Istodax
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 5mg/mL( 2-mL, 5.5-mL single-dose vials)
  • Includes diluent for reconstitution

Cutaneous T-Cell Lymphoma

Indicated for CTCL in patients who have received at least 1 prior systemic therapy

14 mg/m2 IV on days 1, 8, and 15 of 28-d cycle  

Continue until disease progression or intolerable toxicity

Peripheral T-Cell Lymphoma

Indicated for PTCL in patients who have received at least 1 prior systemic therapy

14 mg/m2 IV on days 1, 8, and 15 of 28-d cycle  

Continue until disease progression or intolerable toxicity

Dosage Modifications

Nonhematologic toxicities (except alopecia)

  • Grade 2 or 3 toxicity: Hold dose until toxicity declines to Grade 1 or baseline, then restart at 14 mg/m2
  • If Grade 3 toxicity recurs, hold dose until toxicity returns to Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2
  • Grade 4 toxicity: Hold dose until toxicity declines to Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2
  • Discontinued if Grade 3 or 4 toxicities recur after dose reduction

Hematologic toxicities

  • Grade 3 or 4 neutropenia or thrombocytopenia: Hold dose until toxicity improves to ANC >1.5×109/L and/or platelet count >75×109/L or baseline, then restart at 14 mg/m2
  • Grade 4 febrile (>38.5°C) neutropenia or thrombocytopenia that requires platelet transfusion: Delay dose until the specific cytopenia returns to Grade 1 or baseline, and then permanently reduce dose to 10 mg/m2

Renal impairment

  • No dose adjustment required
  • Pharmacokinetics of romidepsin not influenced by renal impairment

Hepatic impairment

  • Mild: No dose adjustment required
  • Moderate (bilirubin levels >1.5x to ≤3x ULN): Reduce starting dose to 7 mg/m2
  • Severe (bilirubin levels >3x ULN): Reduce starting dose to 5 mg/m2

Safety and efficacy not established

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Interactions

Interaction Checker

and romidepsin

No Results

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Asthenia/fatigue (53-77%)

            Anorexia (23-54%)

            Constipation (12-40%)

            Diarrhea (20-36%)

            Nausea (56-86%)

            Vomiting (34-52%)

            Anemia (19-72%)

            Hypomagnesemia (22-28%)

            Neutropenia (11-66%)

            Thrombocytopenia (17-72%)

            Infections (46-54%)

            <10%

            Hypotension

            EKG changes

            Exfoliative dermatitis

            Pruritus

            Hypocalcemia

            Hypokalemia

            Leukopenia

            Lymphopenia

            Hypoalbuminemia

            Hyperglycemia

            Hyponatremia

            Increased LFTs

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            Warnings

            Contraindications

            Hypersensitivity

            Cautions

            QT prolongation; potassium and magnesium should be within normal limits before administration

            Tumor lysis syndrome has been reported; patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken

            Monitor hematologic parameters; interrupt/discontinue treatment if thrombocytopenia, leukopenia, or anemia becomes severe

            Serious and sometimes fatal infections reported with 30 days after treatment including pneumonia, sepsis, and viral reactivation (eg, Epstein Barr, hepatitis B viruses); risk may be greater in patients with a history of monoclonal antibodies treatment directed against lymphocyte antigens and in patients with disease involvement of the bone marrow

            Avoid during pregnancy, no adequate trials exist; based on MOA, likely to cause fetal harm

            Drug interaction overview

            • Coadministration with other drugs that prolong QT interval (eg, sotalol, dofetilide, erythromycin) may increase risk for serious arrhythmias
            • Binds to estrogen and may reduce effectiveness of oral contraceptives
            • May increase effect of warfarin (prolonged PT, increased INR)
            • Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase romidepsin serum levels
            • Potent CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort) may decrease romidepsin serum levels
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            Pregnancy & Lactation

            Pregnancy

            Based on its mechanism of action and findings from animal studies, may 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

            Advise women of the potential risk to fetus and to avoid becoming pregnant during treatment and for at least 1 month after last dose

            Animal data

            • In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes including embryofetal toxicity and malformations at exposures below those in patients at the recommended dose

            Pregnancy testing

            • Perform pregnancy testing in females of reproductive potential within 7 days before initiating

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for at least 1 month after last dose
            • May reduce the effectiveness of estrogen-containing contraceptives; use alternative methods of non-estrogen containing contraception (eg, condoms, intrauterine devices)
            • Males with female partners of reproductive potential: Use effective contraception to avoid fathering a child during treatment and for at least 1 month after last dose

            Infertility

            • Based on findings in animals, romidepsin has the potential to affect male and female fertility

            Lactation

            • There are no data on presence of drug or its metabolites in human milk, effects on breastfed children, or effects on milk production
            • Advise lactating women not to breastfeed during treatment and for at least 1 week after last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Histone deacetylase (HDAC) inhibitor; induces arrest in the cell cycle at G1 and G2/M phases, which in turn causes cell death

            Absorption

            Peak plasma concentration: 377 ng/mL

            AUC: 1549 ng⋅hr/mL

            Distribution

            Protein bound: 92-94%

            Found to be a BSEP and OATP1 inhibitor

            Metabolism

            Extensive metabolism by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6, and CYP2C19

            Elimination

            Half-life: ~3 hr

            No accumulation of plasma concentration of romidepsin was observed after repeated dosing

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            Administration

            IV Compatibility

            0.9% NaCl

            IV Preparation

            Handle according to recommended safe handling procedures for cytotoxic drugs

            Reconstitute single-dose vials with supplied diluent (10-mg vial with 2.2 mL ; 27.5-mg vial with 5.5 mL)

            Swirl vial contents until there are no visible particles in the resulting solution; reconstituted solution will contain 5 mg/mL

            Withdraw and inject desired amount from vials into 500 mL 0.9% NaCl

            IV Administration

            Administer & dispose according to recommended safe handling procedures for cytotoxic drugs

            Infuse IV over 4 hr

            Administer IV infusion via volumetric infusion pump

            Diluted solution compatible w/ PVC, EVA, PE infusion bags, or glass bottles

            Storage

            Store according to recommended safe handling procedures for cytotoxic drugs

            Unopened vials: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) in the carton; protect from light

            Reconstituted vials: Stable for at least 8 hr at room temperature

            Diluted solutions: Store at room temperature for up to 24 hr

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.