roe-mi-DEP-sin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

• Treatment of cutaneous T-cell lymphoma (CTCL) that has not responded to at least one prior systemic therapy.
• Treatment of peripheral T-cell lymphoma (PTCL) that has not responded to at least one prior therapy.

• Acts as an inhibitor of histone deacetylase (HDAC). HDACs modulate gene expression and transcription factors. Inhibition results in cell cycle arrest and apoptosis.

• ↓extent and spread of CTCL.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Protein Binding: 92–94%.

Metabolism/Excretion: Extensively metabolized, mostly by the CYP3A4 enzyme system.

Half-life: 3 hr.

(response)

Contraindicated in:

• OB: Pregnancy (may cause fetal harm)
• Lactation: Avoid use.

Use Cautiously in:

• Congenital long QT syndrome, history of significant cardiovascular disease, concurrent antiarrhythmics or other medications that cause significant QT interval prolongation (↑ risk of arrhythmias)
• Electrolyte abnormalities (correct magnesium and potassium abnormalities prior to use)
• Moderate to severe hepatic impairment or end-stage renal disease
• Geri: May be more sensitive to drug effects
• Pedi: Safety and effectiveness not established.

CNS: fatigue.

CV: ECG changes, QT interval prolongation.

GI: anorexia, nausea, vomiting.

Hemat: ANEMIA, leukopenia, thrombocytopenia.

Misc: INFECTION (INCLUDING PNEUMONIA, SEPSIS, AND VIRAL REACTIVATION), tumor lysis syndrome.

Drug-Drug:

• May ↑ risk of bleeding withwarfarin or NSAIDs.
• May ↓ effectiveness of estrogen-containing contraceptives (competes with -estradiol for binding to estrogen receptors).
• Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, and voriconazole may ↑ levels and risk of toxicity; avoid concurrent use.
• Rifampin may ↑ levels and risk of toxicity; avoid concurrent use.
• Strong CYP3A4 inducers, including dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine, and phenobarbital may ↓ levels and effectiveness; avoid concurrent use.
• Drugs that inhibit P-gp, including amiodarone, atorvastatin, cyclosporine, dipyridamole, ketoconazole, nelfinavir, quinidine, quinine, reserpine, saquinavir, spironolactone, tacrolimus, and verapamil may ↑ levels and the risk of toxicity; use cautiously.

• IV (Adults): 14 mg/m² on days 1, 8 and 15 of a 28-day cycle, cycle may be repeated every 28 days depending on benefit and patient tolerance; dose may be ↓ to 10 mg/m² if adverse reactions occur.

• Lyophilized powder for injection : 10 mg/vial (contains povidone; enclosed diluent contains propylene glycol and dehydrated alcohol);

• Monitor BP, pulse, respiratory rate, and temperature frequently during administration. Report significant changes
• Monitor ECG and electrolytes at baseline and periodically during therapy. May cause T-wave and ST-segment changes and QT interval prolongation.
• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia and for up to 30 days following therapy. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
• Severe and protracted nausea and vomiting may occur. Administer antiemetics prior to therapy and routinely as indicated. Monitor amount of emesis and health care professional if emesis exceeds guidelines to prevent dehydration. If Grade 2 or 3 nonhematologic toxicity occurs, delay therapy until toxicity returns to Grade 1 or baseline, then therapy may be restarted at 14 mg/m². If Grade 3 toxicity recurs or Grade 4 toxicity occurs, delay therapy until toxicity returns to Grade 1 or baseline and permanently reduce dose to 10 mg/m². Discontinue therapy if Grade 3 or 4 toxicities recur after dose reduction.

• Ensure serum potassium and magnesium are within normal range before administration.
  • Monitor CBC and differential prior to and periodically during therapy. May cause neutropenia or thrombocytopenia. Delay therapy until ANC 1.5 x 10⁹/L and/or platelet count 75 x 10⁹/L or baseline, then restart therapy at 14 mg/m². If Grade 4 febrile (38.5°C) neutropenia or thrombocytopenia that requires platelet transfusion occurs, delay therapy until Grade 1 or baseline, and then permanently ↓ dose to 10 mg/m².

• High Alert:Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings.
• High Alert:Do not confuse romidepsin with romiplostim. Clarify orders that do not include generic and brand names.

IV Administration:

• Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
• Intermittent Infusion: Reconstitute each 10 mg vial with 2.2 mL of supplied diluent. Slowly inject diluent into vial. Swirl until no visible particles in solution. Solution is stable for 8 hrs at room temperature Concentration: 5 mg/mL.
  Diluent: Dilute further in 500 mL of 0.9% NaCl. Do not administer solution that is discolored or contains particulate matter. Diluted solution is stable for 24 hrs at room temperature.
• Rate: Infuse over 4 hr.

• Advise patient to read the Patient Information that comes with medication prior to each dose.
• Instruct patient to notify health care professional promptly if excessive nausea or vomiting, abnormal heartbeat, chest pain, shortness of breath, fever; sore throat; signs of infection (burning with urination, cough, flu like symptoms, muscle aches with or without chest pain, worsening skin problems); bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; ↑ fatigue occurs. Caution patient to avoid crowds and persons with known infections. Infection may occur during and for up to 30 days following therapy. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patient that this medication may have teratogenic effects. Non-hormonal contraception should be used during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the need for periodic lab tests to monitor for side effects.

• ↓extent and spread of CTCL and PTCL.

Istodax

• Risk for infection (Adverse Reactions).

NDC Code^*

• 0069- PFIZER LABORATORIES DIV PFIZER INC
  • 0069-0983- Romidepsin
    • 0069-0983-01- 1 KIT in 1 CARTON (0069-0983-01) * 2 mL in 1 VIAL, GLASS (0069-0972-01) * 2 mL in 1 VIAL, GLASS (0069-0961-01)

• 0703- Teva Parenteral Medicines, Inc.
  • 0703-3125- Romidepsin
    • 0703-3125-08- 1 KIT in 1 CARTON (0703-3125-08) * 2 mL in 1 VIAL, GLASS * 2 mL in 1 VIAL, GLASS

• 59572- Celgene Corporation
  • 59572-984- ISTODAX
    • 59572-984-01- 1 KIT in 1 CARTON (59572-984-01) * 2.4 mL in 1 VIAL, GLASS (59572-973-02) * 2.2 mL in 1 VIAL, GLASS (59572-962-10)