Istodax

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:

• nausea
• vomiting
• tiredness
• loss of appetite
• diarrhea
• constipation, and
• mild itching

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.

 

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.

• Myelosuppression [see WARNINGS AND PRECAUTIONS]
• Infections [see WARNINGS AND PRECAUTIONS]
• Electrocardiographic Changes [see WARNINGS AND PRECAUTIONS]
• Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]

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)