romiDEPsin

romiDEPsin

(roe-mi-dep-sin) ,

Istodax

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

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.

Action

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

Therapeutic effects

↓ extent and spread of CTCL.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Protein Binding: 92–94%.
Metabolism and Excretion: Extensively metabolized, mostly by the CYP3A4 enzyme system.
Half-life: 3 hr.

Time/action profile (response)

ROUTEONSETPEAKDURATION
IV2 mo4–6 mo25–33 mo

Contraindications/Precautions

Contraindicated in: Obstetric: 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; Geriatric: May be more sensitive to drug effects; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)

Cardiovascular

  • ECG changes (most frequent)
  • QT interval prolongation

Gastrointestinal

  • anorexia (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Hematologic

  • anemia (life-threatening)
  • leukopenia
  • thrombocytopenia

Miscellaneous

  • infection (including pneumonia and sepsis) (life-threatening)
  • tumor lysis syndrome

Interactions

Drug-Drug interaction

May ↑ risk of bleeding withwarfarin or NSAIDs.May ↓ effectiveness of estrogen-containing contraceptives (competes with β-estradiol for binding to estrogen receptors). Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, 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.

Route/Dosage

Intravenous (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.

Availability

Lyophilized powder for injection (requires reconstitution): 20 mg/vial (contains povidone; enclosed diluent contains propylene glycol and dehydrated alcohol)

Nursing implications

Nursing assessment

  • Monitor blood pressure, 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.
  • Lab Test Considerations: 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.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • 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. Do not confuse romidepsin with romiplostim. Clarify orders that do not include generic and brand names.
  • Intravenous Administration
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers (see ).
  • Intermittent Infusion: Reconstitute each 10 mg vial with 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. Dilutes solution is stable for 24 hrs at room temperature.
  • Rate: Infuse over 4 hr.

Patient/Family Teaching

  • 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 is breastfeeding.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • ↓ extent and spread of CTCL and PTCL.
Mentioned in ?
References in periodicals archive ?
Decitabine, azacytidine, vorinostat, romidepsin, and belinostat inhibitors are well-known epigenetic inhibitors that were developed to treat several haematopoietic cancers and explored in HCC [147, 148].
The FDA granted accelerated approval to Folotyn (pralatrexate) in 2009 for use in patients with relapsed or refractory PTCL and Istodax (romidepsin) in 2011 for the treatment of PTCL in patients who received at least one prior therapy.
Verastem announced the presentation of new preclinical and Phase 1 clinical data from an investigator-sponsored study evaluating the safety and activity of oral duvelisib in combination with romidepsin or bortezomib in relapsed or refractory T-cell lymphomas at the American Society of Hematology 2017 Annual Meeting held December 9-12, 2017 in Atlanta.
1 March 2011 - US Celgene Corporation (NASDAQ: CELG) said on Monday that the US Food and Drug Administration (FDA) has granted Priority Review to its supplemental New Drug Application (sNDA) regarding ISTODAX (romidepsin) for injection for the treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.
HDAC inhibitors, such as valproic acid (VPA), butyric acid, trichostatin A, vorinostat/SAHA, panobinostat, entinostat, givinostat, and romidepsin, have been well characterized, both in vivo and in vitro (Table 1).
The transaction brings to Celgene ISTODAX (romidepsin), an approved therapy for the treatment of cutaneous T-cell lymphoma (CTCL), providing a strategic fit and expanding the company's presence in critical blood cancers.
In the other Phase 1 study, patients received duvelisib monotherapy 25mg or 75mg twice daily for one month as a lead-in to a combination regimen with romidepsin or bortezomib.
Romidepsin (stock solution: 1 mM in DMSO), entinostat (stock solution: 5 mM in DMSO), and irinotecan (stock solution: 10 mM in DMSO) were from Selleckchem; hydroxyurea (stock solution: 100 mM in PBS) was from Sigma-Aldrich; and imatinib (stock solution: 1 mM in DMSO) and marbostat-100 (stock solution: 10 mM in DMSO) were synthesized by A.
On the basis of chemical structures and enzymatic activities, HDACIs are (Figure 3) (10) chemically classified as hydroxamates (vorinostat, panobinostat, givinostat, quisinostat, abexinostat, belinostat, tefinostat, resminostat, pracinostat), benzamides (entinostat, mocetinostat, chidamide), aliphatic acids (valproic acid), and cyclic peptides (romidepsin).
The confirmatory study is expected to start in the second half of 2019; Initiating additional investigational studies of duvelisib as a monotherapy and in combination with other anti-cancer agents, such as checkpoint inhibitors, in both hematological and solid tumor malignancies; Working with the LLS to advance the PTCL program including the expansion of the Phase 2 combination study of duvelisib and romidepsin for patients with relapsed or refractory PTCL; Additional ex-U.S.
The use of HDAC inhibitors, vorinostat and romidepsin, has been approved by the FDA for the treatment of cutaneous T-cell lymphoma.
All patients were previously on at least three prior therapies, including belinostat, pralatrexate and romidepsin. Additionally, data demonstrate an initial signal in CTCL, with the first patient enrolled achieving a CR.