Istodax

Last updated on RxList: 4/7/2021
Istodax Side Effects Center

What Is Istodax?

Istodax (romidepsin) for Injection is a histone deacetylase (HDAC) inhibitor used to treat T-cell lymphoma affecting the skin (cutaneous T-cell lymphoma, or CTCL). Istodax is usually given after other medications have been tried without successful treatment of symptoms.

What Are Side Effects of Istodax?

Common side effects of Istodax include:

Dosage for Istodax

The recommended dose of Istodax is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle.

What Drugs, Substances, or Supplements Interact with Istodax?

Istodax may interact with dexamethasone, isoniazid, St. John's wort, antibiotics, antifungal medications, antidepressants, anti-malarials, barbiturates, blood thinners, heart or blood pressure medications, heart rhythm medicines, HIV or AIDS medications, medicines used to prevent organ transplant rejection, medicine to prevent or treat nausea and vomiting, medicines to treat a psychiatric disorder, migraine headache medicines, narcotics, or seizure medications. Tell your doctor all medications and supplements you use.

Istodax During Pregnancy and Breastfeeding

Istodax is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this drug passes into breast milk and may harm nursing infants. Breastfeeding while using Istodax is not recommended.

Additional Information

Our Istodax (romidepsin) for Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Skin Cancer Symptoms, Types, Images See Slideshow
Istodax Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

You may get infections more easily, even serious or fatal infections, during treatment and within 30 days afterward. Call your doctor right away if you have signs of infection such as:

  • fever, flu symptoms, muscle aches;
  • worsening skin symptoms;
  • burning when you urinate; or
  • chest discomfort, feeling short of breath.

Also call your doctor at once if you have:

  • chest pain, feeling short of breath;
  • fast or pounding heartbeats, fluttering in your chest, sudden dizziness (like you might pass out);
  • low platelets--easy bruising, unusual bleeding, purple or red spots under your skin;
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or
  • signs of tumor cell breakdown--confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth.

Common side effects may include:

  • nausea, vomiting, diarrhea;
  • loss of appetite; or
  • tiredness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Istodax (Romidepsin for Injection)

Istodax Professional Information

SIDE EFFECTS

The following adverse reactions are described in more detail in other sections of the prescribing information.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Cutaneous T-Cell Lymphoma

The safety of ISTODAX was evaluated in 185 patients with CTCL in 2 single arm clinical studies in which patients received a starting dose of 14 mg/m2. The mean duration of treatment in these studies was 5.6 months (range: <1 to 83.4 months).

Common Adverse Reactions

Table 2 summarizes the most frequent adverse reactions (>20%) regardless of causality using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 3.0). Due to methodological differences between the studies, the AE data are presented separately for Study 1 and Study 2. Adverse reactions are ranked by their incidence in Study 1. Laboratory abnormalities commonly reported (>20%) as adverse reactions are included in Table 2.

Table 2. Adverse Reactions Occurring in >20% of Patients in Either CTCL Study (N=185)

Adverse Reactions n (%) Study 1
(n=102)
Study 2
(n=83)
All grades Grade 3 or 4 All grades Grade 3 or 4
Any adverse reactions 99 (97) 36 (35) 83 (100) 68 (82)
Nausea 57 (56) 3 (3) 71 (86) 5 (6)
Asthenia/Fatigue 54 (53) 8 (8) 64 (77) 12 (14)
Infections 47 (46) 11 (11) 45 (54) 27 (33)
Vomiting 35 (34) 1 (<1) 43 (52) 8 (10)
Anorexia 23 (23) 1 (<1) 45 (54) 3 (4)
Hypomagnesemia 22 (22) 1 (<1) 23 (28) 0
Diarrhea 20 (20) 1 (<1) 22 (27) 1 (1)
Pyrexia 20 (20) 4 (4) 19 (23) 1 (1)
Anemia 19 (19) 3 (3) 60 (72) 13 (16)
Thrombocytopenia 17 (17) 0 54 (65) 12 (14)
Dysgeusia 15 (15) 0 33 (40) 0
Constipation 12 (12) 2 (2) 32 (39) 1 (1)
Neutropenia 11 (11) 4 (4) 47 (57) 22 (27)
Hypotension 7 (7) 3 (3) 19 (23) 3 (4)
Pruritus 7 (7) 0 26 (31) 5 (6)
Hypokalemia 6 (6) 0 17 (20) 2 (2)
Dermatitis/Exfoliative dermatitis 4 (4) 1 (<1) 22 (27) 7 (8)
Hypocalcemia 4 (4) 0 43 (52) 5 (6)
Leukopenia 4 (4) 0 38 (46) 18 (22)
Lymphopenia 4 (4) 0 47 (57) 31 (37)
Alanine aminotransferase increased 3 (3) 0 18 (22) 2 (2)
Aspartate aminotransferase increased 3 (3) 0 23 (28) 3 (4)
Hypoalbuminemia 3 (3) 1 (<1) 40 (48) 3 (4)
Electrocardiogram ST-T wave changes 2 (2) 0 52 (63) 0
Hyperglycemia 2 (2) 2 (2) 42 (51) 1 (1)
Hyponatremia 1 (<1) 1 (<1) 17 (20) 2 (2)
Hypermagnesemia 0 0 22 (27) 7 (8)
Hypophosphatemia 0 0 22 (27) 8 (10)
Hyperuricemia 0 0 27 (33) 7 (8)

Serious Adverse Reactions

Infections were the most common type of SAE reported in both studies with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection. Serious adverse reactions reported in >2% of patients in Study 1 were sepsis and pyrexia (3%). In Study 2, serious adverse reactions in >2% of patients were fatigue (7%), supraventricular arrhythmia, central line infection, neutropenia (6%), hypotension, hyperuricemia, edema (5%), ventricular arrhythmia, thrombocytopenia, nausea, leukopenia, dehydration, pyrexia, aspartate aminotransferase increased, sepsis, catheter related infection, hypophosphatemia and dyspnea (4%).

There were eight deaths not due to disease progression. In Study 1, there were two deaths: one due to cardiopulmonary failure and one due to acute renal failure. There were six deaths in Study 2: four due to infection and one each due to myocardial ischemia and acute respiratory distress syndrome.

Discontinuations

Discontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Discontinuations occurring in at least 2% of patients in either study included infection, fatigue, dyspnea, QT prolongation, and hypomagnesemia.

Peripheral T-Cell Lymphoma

The safety of ISTODAX was evaluated in 178 patients with PTCL in a sponsor-conducted pivotal study (Study 3) and a secondary NCI-sponsored study (Study 4) in which patients received a starting dose of 14 mg/m2. The mean duration of treatment and number of cycles were 5.6 months and 6 cycles in Study 3 and 9.6 months and 8 cycles in Study 4.

Common Adverse Reactions

Table 3 summarizes the most frequent adverse reactions (≥10%) regardless of causality, using the NCI-CTCAE, Version 3.0. The AE data are presented separately for Study 3 and Study 4. Laboratory abnormalities commonly reported (≥10%) as adverse reactions are included in Table 3.

Table 3. Adverse Reactions Occurring in ≥10% of Patients with PTCL in Study 3 and Corresponding Incidence in Study 4 (N=178)

Adverse Reactions n (%) Study 3
(N=131)
Study 4
(N=47)
All grades Grade 3 or 4 All grades Grade 3 or 4
Any adverse reactions 128 (97) 88 (67) 47 (100) 40 (85)
Gastrointestinal disorders
  Nausea 77 (59) 3 (2) 35 (75) 3 (6)
  Vomiting 51 (39) 6 (5) 19 (40) 4 (9)
  Diarrhea 47 (36) 3 (2) 17 (36) 1 (2)
  Constipation 39 (30) 1 (<1) 19 (40) 1 (2)
  Abdominal pain 18 (14) 3 (2) 6 (13) 1 (2)
  Stomatitis 14 (11) 0 3 (6) 0
General disorders and administration site conditions
  Asthenia/Fatigue 72 (55) 11 (8) 36 (77) 9 (19)
  Pyrexia 46 (35) 8 (6) 22 (47) 8 (17)
  Chills 14 (11) 1 (<1) 8 (17) 0
  Edema peripheral 13 (10) 1 (<1) 3 (6) 0
Blood and lymphatic system disorders
  Thrombocytopenia 53 (41) 32 (24) 34 (72) 17 (36)
  Neutropenia 39 (30) 26 (20) 31 (66) 22 (47)
  Anemia 33 (25) 14 (11) 29 (62) 13 (28)
  Leukopenia 16 (12) 8 (6) 26 (55) 21 (45)
Metabolism and nutrition disorders
  Anorexia 37 (28) 2 (2) 21 (45) 1 (2)
  Hypokalemia 14 (11) 3 (2) 8 (17) 1 (2)
Nervous system disorders
  Dysgeusia 27 (21) 0 13 (28) 0
  Headache 19 (15) 0 16 (34) 1 (2)
Respiratory, thoracic and mediastinal disorders
  Cough 23 (18) 0 10 (21) 0
  Dyspnea 17 (13) 3 (2) 10 (21) 2 (4)
Investigations
  Weight decreased 14 (11) 0 7 (15) 0
Cardiac disorders
  Tachycardia 13 (10) 0 0 0

Serious Adverse Reactions

Infections were the most common type of SAE reported. In Study 3, twenty-six patients (20%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, eleven patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections. Serious adverse reactions reported in ≥2% of patients in Study 3 were pyrexia (8%), pneumonia, sepsis, vomiting (5%), cellulitis, deep vein thrombosis, (4%), febrile neutropenia, abdominal pain (3%), chest pain, neutropenia, pulmonary embolism, dyspnea, and dehydration (2%). In Study 4, serious adverse reactions in ≥2 patients were pyrexia (17%), aspartate aminotransferase increased, hypotension (13%), anemia, thrombocytopenia, alanine aminotransferase increased (11%), infection, dehydration, dyspnea (9%), lymphopenia, neutropenia, hyperbilirubinemia, hypocalcemia, hypoxia (6%), febrile neutropenia, leukopenia, ventricular arrhythmia, vomiting, hypersensitivity, catheter related infection, hyperuricemia, hypoalbuminemia, syncope, pneumonitis, packed red blood cell transfusion, and platelet transfusion (4%).

Reactivation of hepatitis B virus infection has occurred in 1% of patients with PTCL in clinical trials in Western populations enrolled in Study 3 and Study 4 [see WARNINGS AND PRECAUTIONS].

Deaths due to all causes within 30 days of the last dose of ISTODAX occurred in 7% of patients in Study 3 and 17% of patients in Study 4. In Study 3, there were 5 deaths unrelated to disease progression that were due to infections, including multi-organ failure/sepsis, pneumonia, septic shock, candida sepsis, and sepsis/cardiogenic shock. In Study 4, there were 3 deaths unrelated to disease progression that were due to sepsis, aspartate aminotransferase elevation in the setting of Epstein Barr virus reactivation, and death of unknown cause.

Discontinuations

Discontinuation due to an adverse event occurred in 19% of patients in Study 3 and in 28% of patients in Study 4. In Study 3, thrombocytopenia and pneumonia were the only events leading to treatment discontinuation in at least 2% of patients. In Study 4, events leading to treatment discontinuation in ≥2 patients were thrombocytopenia (11%), anemia, infection, and alanine aminotransferase increased (4%).

Read the entire FDA prescribing information for Istodax (Romidepsin for Injection)

© Istodax Patient Information is supplied by Cerner Multum, Inc. and Istodax Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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