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ROMIDEPSIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Romidepsin is a histone deacetylase (HDAC) inhibitor.

Specific Substances

    1) FK228
    2) FR901228
    3) NSC 630176
    4) CAS 128517-07-7
    1.2.1) MOLECULAR FORMULA
    1) C(24)H(36)N(4)O(6)S(2) (Prod Info ISTODAX(R) intravenous injection, 2009).

Available Forms Sources

    A) FORMS
    1) Romidepsin is a parenteral medication available in a kit containing 1 vial of romidepsin 10 mg and 1 vial of diluent (2 mL) (Prod Info ISTODAX(R) intravenous injection, 2009).
    B) USES
    1) Romidepsin is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy(Prod Info ISTODAX(R) intravenous injection, 2009).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Romidepsin is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
    B) PHARMACOLOGY: Romidepsin is a histone deacetylase (HDAC) inhibitor; it causes the accumulation of acetylated histones and induces cell cycle arrest and apoptosis of some cancer cell lines.
    C) EPIDEMIOLOGY: Overdose of romidepsin is rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: LESS SEVERE: Nausea, vomiting, and fatigue. SEVERE: Risk of QT prolongation or treatment-related ECG changes, infection, sepsis, pyrexia, supraventricular dysrhythmia, leukopenia, anemia and thrombocytopenia. During clinical trials, most deaths were related to disease progression. In a small number of cases, the cause of death was due to cardiopulmonary failure, acute renal failure, infection, myocardial ischemia and acute respiratory distress syndrome.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: At the time of this review, there are no reports of overdose with romidepsin. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses; primarily nausea and vomiting, leucopenia, thrombocytopenia, QTc prolongation and possibly ventricular dysrhythmias.
    0.2.20) REPRODUCTIVE
    A) Romidepsin is classified as FDA pregnancy category D. In animal studies, teratogenic and embryolethal effects were observed.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, the manufacturer reports no carcinogenic studies have been done with romidepsin.

Laboratory Monitoring

    A) Obtain an ECG and institute continuous cardiac monitoring. Alterations in T-wave and ST-segment have been observed with therapeutic use. Patients with a history of cardiovascular disease or congenital long QT syndrome may be at risk for QT prolongation.
    B) Monitor serial CBC with differential and platelet count.
    C) Monitor electrolytes, in particular potassium and magnesium.
    D) Monitor fluid status.
    E) Monitor for clinical signs of infection.
    F) Monitor for evidence of allergic response.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor patient for clinical signs of infection.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic. Institute cardiac monitoring, correct electrolyte abnormalities, and replace fluids lost through vomiting or diarrhea. Monitor serial CBC with differential. Granulocyte colony stimulating factors or blood products may be necessary.
    C) DECONTAMINATION
    1) Decontamination is not necessary, romidepsin is administered parenterally.
    D) AIRWAY MANAGEMENT
    1) Assess airway patency. Oxygen therapy may be necessary for patients who develop cardiac or pulmonary failure, but this is rare with therapeutic use.
    E) ANTIDOTE
    1) None.
    F) MYELOSUPPRESSION
    1) For severe neutropenia or neutropenic sepsis, administer filgrastim 5 mcg/kg/day subcutaneously, or sargramostim 250 mcg/m(2)/day. If the severity of overdose makes bone marrow failure likely, consider admission to a bone marrow transplant unit.
    G) HYPOTENSIVE EPISODE
    1) Treat hypotension with intravenous fluids; if hypotension persists, administer vasopressors.
    H) TORSADE DE POINTES
    1) Therapeutic doses of romidepsin may cause prolongation of the QT interval. TORSADES DE POINTES: Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Hemodynamically unstable patients require electrical cardioversion. Treat stable patients with magnesium and/or atrial overdrive pacing. Correct electrolyte abnormalities (hypomagnesemia, hypokalemia, hypocalcemia). MAGNESIUM SULFATE/DOSE: ADULT: 2 g IV over 1 to 2 min, repeat 2 g bolus and begin infusion of 0.5 to 1 g/hr if dysrhythmias recur. CHILD: 25 to 50 mg/kg diluted to 10 mg/mL; infuse IV over 5 to 15 min. OVERDRIVE PACING: Begin at 130 to 150 beats/min, decrease as tolerated. Avoid class Ia (quinidine, disopyramide, procainamide), class Ic (flecainide, encainide, propafenone) and most class III antidysrhythmics (N-acetylprocainamide, sotalol).
    I) ENHANCED ELIMINATION
    1) Hemodialysis and hemoperfusion are UNLIKELY to be of value due to the high degree of protein binding of romidepsin.
    J) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: Patients with significant overdose should be sent to a health care facility for evaluation and treatment as necessary.
    2) ADMISSION CRITERIA: Patients who remain symptomatic, despite treatment should be admitted.
    3) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    K) PITFALLS
    1) When managing a suspected overdose of romidepsin, the possibility of multidrug involvement should be considered.
    L) PHARMACOKINETICS
    1) Romidepsin displays linear pharmacokinetics with doses ranging from 1 to 24.9 mg/m(2). Mean Plasma Cmax is 377 ng/mL after therapeutic use (therapeutic dose is 14 mg/m(2) on days 1, 8 and 15 of a 28-day cycle). Romidepsin is approximately 94% protein bound in plasma and primarily binds to alpha 1-acid-glycoprotein (AAG) with a concentration range of 50 ng/mL to 1000 ng/mL. The terminal half-life after a 4-hour infusion of 14 mg/m(2) is approximately 3 hours. No accumulation of romidepsin was observed in the plasma with repeated dosing.
    M) DIFFERENTIAL DIAGNOSIS
    1) The differential diagnosis for romidepsin toxicity should include other chemotherapeutic agents that may cause the same systemic effects.

Range Of Toxicity

    A) A specific toxic dose has not been established.

Clinical Effects

Summary Of Exposure

    A) USES: Romidepsin is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
    B) PHARMACOLOGY: Romidepsin is a histone deacetylase (HDAC) inhibitor; it causes the accumulation of acetylated histones and induces cell cycle arrest and apoptosis of some cancer cell lines.
    C) EPIDEMIOLOGY: Overdose of romidepsin is rare.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: LESS SEVERE: Nausea, vomiting, and fatigue. SEVERE: Risk of QT prolongation or treatment-related ECG changes, infection, sepsis, pyrexia, supraventricular dysrhythmia, leukopenia, anemia and thrombocytopenia. During clinical trials, most deaths were related to disease progression. In a small number of cases, the cause of death was due to cardiopulmonary failure, acute renal failure, infection, myocardial ischemia and acute respiratory distress syndrome.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: At the time of this review, there are no reports of overdose with romidepsin. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses; primarily nausea and vomiting, leucopenia, thrombocytopenia, QTc prolongation and possibly ventricular dysrhythmias.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) Pyrexia occurred in 20% and 23% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) PROLONGED QT INTERVAL
    1) WITH THERAPEUTIC USE
    a) Treatment-related alterations in ECGs (including T-wave and ST-segment changes) have developed during clinical trials with romidepsin. Although QT prolongation has not been observed during clinical studies, patients with a history of cardiovascular disease or congenital long QT syndrome may be at risk to develop QT prolongation (Prod Info ISTODAX(R) intravenous injection, 2009).
    B) SUPRAVENTRICULAR ARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Supraventricular arrhythmia and ventricular arrhythmia was reported in greater than 2% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    C) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension occurred in 7% and 23% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    D) CARDIORESPIRATORY ARREST
    1) WITH THERAPEUTIC USE
    a) Death due to cardiopulmonary failure was reported in 2 patients during therapeutic use of romidepsin (Prod Info ISTODAX(R) intravenous injection, 2009).
    E) MYOCARDIAL ISCHEMIA
    1) WITH THERAPEUTIC USE
    a) Death due to myocardial ischemia was reported in a small number of patients during therapeutic use of romidepsin (Prod Info ISTODAX(R) intravenous injection, 2009).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) ASTHENIA
    1) WITH THERAPEUTIC USE
    a) Asthenia/fatigue occurred in 53% and 77% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH THERAPEUTIC USE
    a) Nausea occurred in 56% and 86% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    B) VOMITING
    1) WITH THERAPEUTIC USE
    a) Vomiting occurred in 34% and 52% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    C) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea was reported in 7% and 20% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Elevations in alanine aminotransferase and aspartate aminotransferase were observed in patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenia was reported in 17% and 65% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    B) ANEMIA
    1) WITH THERAPEUTIC USE
    a) Anemia was reported in 19% and 72% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    C) NEUTROPENIA
    1) WITH THERAPEUTIC USE
    a) Neutropenia was reported in 11% and 57% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) Pruritus was reported in 7% and 31% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).
    B) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Exfoliative dermatitis was reported in 4% and 27% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERGLYCEMIA
    1) WITH THERAPEUTIC USE
    a) Hyperglycemia occurred in 2% and 51% of patients treated with romidepsin in 2, multicenter, single-arm studies of patients (n=185) with cutaneous T-cell lymphoma (CTCL) receiving 14 mg/m(2) on days 1, 8, and 15 in a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2009)

Reproductive

    3.20.1) SUMMARY
    A) Romidepsin is classified as FDA pregnancy category D. In animal studies, teratogenic and embryolethal effects were observed.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) RATS: Embryo-fetal effects, including retina, rotated limbs, and sternal ossification, have been observed at doses greater than or equal to 0.1 mg/kg/day (0.2% of the human exposure at a 14 mg/m(2)/week dose, based on AUC) or greater doses (Prod Info ISTODAX(R) intravenous injection, 2014).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified romidepsin as FDA pregnancy category D (Prod Info ISTODAX(R) intravenous injection, 2014).
    2) Romidepsin may cause fetal harm if administered during pregnancy; therefore, if this drug is used during pregnancy, or if the patient becomes pregnant during therapy, the patient should be made aware of the potential fetal hazard (Prod Info ISTODAX(R) intravenous injection, 2014).
    B) ANIMAL STUDIES
    1) RATS: Substantial resorption or post-implantation loss has been observed in at 0.5 mg/kg/day doses during organogenesis (Prod Info ISTODAX(R) intravenous injection, 2014).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) If romidepsin is used in a woman who is nursing, a decision should be made to discontinue either breastfeeding or the drug, taking into account the importance of this drug to the mother (Prod Info ISTODAX(R) intravenous injection, 2014).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) MALE RATS: Testicular degeneration was observed in male rats administered 0.33 mg/kg/dose (2 mg/m(2)/dose) (approximately 2% the human exposure at 14 mg/m(2)/dose, based on AUC). A similar effect was seen in mice receiving a higher dose after 4 weeks of exposure. Seminal vesicles and prostate organ weights were decreased in a separate study after 4 weeks of 0.1 mg/kg/day (0.6 mg/m(2)/day) (approximately 30% the estimated human daily dose, based on body surface area) (Prod Info ISTODAX(R) intravenous injection, 2014).
    2) FEMALE RATS: Atrophy of the ovary, uterus, vagina, and mammary gland were observed at 0.1 mg/kg/dose (0.6 mg/m(2)/dose) (approximately 0.3% the human exposure at 14 mg/m(2)/dose, based on AUC). Maturation arrest of the ovarian follicles and decreased ovarian weight were observed in a separate study after 4 weeks of 0.1mg/kg/day (0.6 mg/m(2)/day) (approximately 30% the estimated human daily dose, based on body surface area) (Prod Info ISTODAX(R) intravenous injection, 2014).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, the manufacturer reports no carcinogenic studies have been done with romidepsin.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, the manufacturer reports no carcinogenic studies have been done with romidepsin (Prod Info ISTODAX(R) intravenous injection, 2009).

Genotoxicity

    A) Romidepsin was found not to be mutagenic in vitro when tested in mice. Romidepsin showed no evidence of clastogenicity in in vivo rat bone marrow micronucleus assays when tested to the maximum tolerated dose of 1 mg/kg (6 mg/m(2)) in male rats and 3 mg/kg (18 mg/m(2)) in female rats, which is up to 1.3-fold the recommended human dose based on body surface area (Prod Info ISTODAX(R) intravenous injection, 2009).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain an ECG and institute continuous cardiac monitoring. Alterations in T-wave and ST-segment have been observed with therapeutic use. Patients with a history of cardiovascular disease or congenital long QT syndrome may be at risk for QT prolongation.
    B) Monitor serial CBC with differential and platelet count.
    C) Monitor electrolytes, in particular potassium and magnesium.
    D) Monitor fluid status.
    E) Monitor for clinical signs of infection.
    F) Monitor for evidence of allergic response.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients who remain symptomatic despite treatment should be admitted.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a Poison Center for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Patients with significant overdose should be sent to a health care facility for evaluation and treatment as necessary.

Monitoring

    A) Obtain an ECG and institute continuous cardiac monitoring. Alterations in T-wave and ST-segment have been observed with therapeutic use. Patients with a history of cardiovascular disease or congenital long QT syndrome may be at risk for QT prolongation.
    B) Monitor serial CBC with differential and platelet count.
    C) Monitor electrolytes, in particular potassium and magnesium.
    D) Monitor fluid status.
    E) Monitor for clinical signs of infection.
    F) Monitor for evidence of allergic response.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not necessary, romidepsin is administered parenterally.
    6.5.2) PREVENTION OF ABSORPTION
    A) Decontamination is not necessary, romidepsin is administered parenterally.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Romidepsin is administered parenterally; refer to parenteral section for information on specific treatment.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    B) DISPOSAL GUIDELINES
    1) LABELING: Cytotoxic waste should be regarded as HAZARDOUS or TOXIC waste. It must be handled differently from other trash and should be clearly labeled "HAZARDOUS CHEMICAL WASTE - DISPOSE OF PROPERLY" (Anon, 1990).
    2) CONTAINER: Cytotoxic waste may be placed in a leakproof, puncture resistant container which is then placed in disposable wire-tie or sealable 4-mil-thick polyethylene or 2-mil-thick propylethylene bags. These bags should be colored so as to be easily distinguishable from other trash bags, and labeled with a "Cytotoxic Hazard" label (Jeffrey LP, Anderson RW & Fortner CL et al, 1984; Anon, 1986).
    3) SPILL PROCEDURE: Spills should be cleaned up immediately by a person trained in such procedures and wearing appropriate protective clothing (commercial spill kits are available) (Anon, 1990). The area of the spill should be marked so that while cleanup is occurring someone in the area is not accidentally contaminated. Broken glass should be carefully removed possibly by using a scoop. A broom or mop is not advised due to the risk of further contamination of the environment.
    4) DISPOSAL: Cytotoxic waste may be disposed of at an EPA permitted hazardous waste incinerator, an EPA permitted hazardous waste burial site, or by a licensed hazardous waste disposal company and in accordance with all applicable state, federal, and local regulations (Anon, 1990; Jeffrey LP, Anderson RW & Fortner CL et al, 1984).
    C) SMALL SPILL DECONTAMINATION
    1) SUMMARY: Small spills (less than 5 milliliters or 5 grams) should be cleaned immediately by personnel wearing double surgical latex gloves, disposable gown, a face shield or splash goggles and a dust/mist respirator mask (Anon, 1986; Chasse & Gaudet, 1992; Peters, 1995).
    a) CLEAN UP PROCEDURE: Liquids should be adsorbed with gauze pads; solids should be wiped up with wet absorbent gauze (Anon, 1986).
    b) DECONTAMINATION: The spill area should be further decontaminated by THREE washings using a detergent solution (germicidal solutions are not recommended) followed by a rinse of clear water (Anon, 1986).
    c) DISPOSAL: All materials used in the cleanup procedure should be disposed of in the cytotoxic waste bag (Anon, 1986).
    D) LARGE SPILL DECONTAMINATION
    1) SUMMARY: Large spills (greater than 5 milliliters or 5 grams) should be covered immediately with absorbent sheets or spill control pads to reduce the spread. If a powder was spilled use a damp cloth or towel (Anon, 1986).
    a) SECURE AREA: Restrict access to the spill area and take precautions to minimize the generation of aerosols (Anon, 1986).
    b) PERSONNEL PROTECTION: Protective clothing should be worn as with the small spill with the addition of a respirator or breathing apparatus when there is an airborne contamination danger (Anon, 1986).
    c) DECONTAMINATION: The area should be further decontaminated by THREE washings using a detergent solution (germicidal solutions are not recommended) followed by a rinse of clear water (Anon, 1986).
    d) DISPOSAL: All materials used in the cleanup procedure should be disposed of in the cytotoxic waste bag (Anon, 1986).
    E) PERSONNEL PROTECTION
    1) PROTECTIVE CLOTHING: A double layer of disposable surgical latex gloves, protective disposable gowns (non-permeable, made of lint-free, low-permeability fabric with a solid front, long sleeves, and tight-fitting elastic or knit cuffs) with cuff tucked into glove, eye protection (splash goggles), breathing apparatus, in ventilated cabinets when there is airborne contamination danger (Centers for Disease Control and Prevention (CDC), 2012; Anon, 1990a; Anon, 1986).
    2) DECONTAMINATION/CLOTHING: Laundering of non-disposable materials has not been demonstrated to remove cytotoxic contaminants. DISPOSAL: The appropriate procedure for the disposal of these materials should be determined by the institution (or as required by state or local regulation or disposal contractor) (Centers for Disease Control and Prevention (CDC), 2012; Anon, 1990a).

Enhanced Elimination

    A) LACK OF EFFICACY
    1) HEMODIALYSIS
    a) No clinical reports are available. However, hemodialysis and hemoperfusion are UNLIKELY to be of value due to the high degree of protein binding of romidepsin.

Range Of Toxicity

Summary

    A) A specific toxic dose has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) The recommended dose is 14 mg/m(2) given intravenously over 4 hours on days 1, 8, and 15 on a 28-day cycle (Prod Info ISTODAX(R) intravenous injection, 2014).
    7.2.2) PEDIATRIC
    A) Safety and efficacy in the pediatric population have not been established (Prod Info ISTODAX(R) intravenous injection, 2014).

Maximum Tolerated Exposure

    A) A specific toxic dose has not been established.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from the acetylated lysine residues in histones, resulting in the modulation of gene expression. In addition, HDACs remove acetyl groups from non-histone proteins, such as transcription factors. In vitro, romidepsin causes the accumulation of acetylated histones and induces cell cycle arrest and apoptosis of some cancer cell lines, with IC(50) values in the nanomolar range (Prod Info ISTODAX(R) intravenous injection, 2009).

Physicochemical

Physical Characteristics

    A) Romidepsin is a white powder at room temperature (Prod Info ISTODAX(R) intravenous injection, 2009).

Molecular Weight

    A) 540.71 (Prod Info ISTODAX(R) intravenous injection, 2009).

References

General Bibliography

    1) American Heart Association: 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2005; 112(24 Suppl):IV 1-203. Available from URL: http://circ.ahajournals.org/content/vol112/24_suppl/. As accessed 12/14/2005.
    2) Anon: ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990; 47:1033-1048.
    3) Anon: ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990a; 47:1033-1049.
    4) Anon: OSHA work-practice guidelines for personnel dealing with cytotoxic (antineoplastic) drugs. Am J Hosp Pharm 1986; 43:1193-1204.
    5) Beauchesne MF & Shalansky SJ: Nonchemotherapy drug-induced agranulocytosis: a review of 118 patients treated with colony-stimulating factors. Pharmacotherapy 1999; 19(3):299-305.
    6) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    7) Centers for Disease Control and Prevention (CDC): NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2012. Centers for Disease Control and Prevention (CDC). Atlanta, GA. 2012. Available from URL: http://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf. As accessed 2013-05-14.
    8) Charlton NP , Lawrence DT , Brady WJ , et al: Termination of drug-induced torsades de pointes with overdrive pacing. Am J Emerg Med 2010; 28(1):95-102.
    9) Chasse MA & Gaudet S: Safe handling of cytotoxic agents. AARN News Letter 1992; 48:14-15.
    10) Drew BJ, Ackerman MJ, Funk M, et al: Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2010; 55(9):934-947.
    11) Hartman LC, Tschetter LK, Habermann TM, et al: Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.. N Engl J Med 1997; 336:1776-1780.
    12) Jeffrey LP, Anderson RW & Fortner CL et al: Recommendations for handling cytotoxic agents. National Study Commission on Cytotoxic Exposure (Sept), 1984.
    13) Keren A, Tzivoni D, & Gavish D: Etiology, warning signs and therapy of torsade de pointes: a study of 10 patients. Circulation 1981; 64:1167-1174.
    14) Khan IA & Gowda RM: Novel therapeutics for treatment of long-QT syndrome and torsade de pointes. Int J Cardiol 2004; 95(1):1-6.
    15) Kleinman ME, Chameides L, Schexnayder SM, et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 14: pediatric advanced life support. Circulation 2010; 122(18 Suppl.3):S876-S908.
    16) Link MS, Berkow LC, Kudenchuk PJ, et al: Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132(18 Suppl 2):S444-S464.
    17) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    18) Neumar RW , Otto CW , Link MS , et al: Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18 Suppl 3):S729-S767.
    19) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    20) Peberdy MA , Callaway CW , Neumar RW , et al: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care science. Part 9: post–cardiac arrest care. Circulation 2010; 122(18 Suppl 3):S768-S786.
    21) Perticone F, Ceravolo R, & Cuccurullo O: Prolonged magnesium sulfate infusion in the treatment of ventricular tachycardia in acquired long QT syndrome. Clin Drug Inverst 1997; 13:229-236.
    22) Peters BG: Technical considerations in the preparation and dispensing of chemotherapy. Top Hosp Pharm Manage 1995; 14:78-88.
    23) Product Information: ISTODAX(R) intravenous injection, romidepsin intravenous injection. Celgene Corporation (per Manufacturer), Summit, NJ, 2014.
    24) Product Information: ISTODAX(R) intravenous injection, romidepsin intravenous injection. Gloucester Pharmaceuticals, Inc., Cambridge, MA, 2009.
    25) Product Information: Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, isoproterenol HCl intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection. Hospira, Inc. (per FDA), Lake Forest, IL, 2013.
    26) Product Information: LEUKINE(R) injection, sargramostim injection. Berlex, Seattle, WA, 2006.
    27) Product Information: NEUPOGEN(R) injection, filgrastim injection. Amgen,Inc, Thousand Oaks, CA, 2006.
    28) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    29) Product Information: magnesium sulfate heptahydrate IV, IM injection, solution, magnesium sulfate heptahydrate IV, IM injection, solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2009.
    30) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
    31) Smith WM & Gallagher JJ: "Les torsades de pointes": an unusual ventricular arrhythmia. Ann Intern Med 1980; 93:578-584.
    32) Stull DM, Bilmes R, Kim H, et al: Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm 2005; 62(1):83-87.