SIDE EFFECTS

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

• Hematologic Toxicity.
• Infection.
• Hepatotoxicity.
• Tumor Lysis Syndrome.
• Gastrointestinal Toxicity.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Beleodaq may not reflect the rates observed in practice.

Adverse Reactions In Patients With Peripheral T-Cell Lymphoma

The safety of Beleodaq was evaluated in 129 patients with relapsed or refractory PTCL in the single arm clinical trial in which patients were administered Beleodaq at a dosage of 1,000 mg/m² administered over 30 minutes by IV infusion once daily on Days 1-5 of a 21-day cycle . The median duration of treatment was 2 cycles (range 1 – 33 cycles).

The most common adverse reactions observed in the trial of patients with relapsed or refractory PTCL treated with Beleodaq were nausea, fatigue, pyrexia, anemia, and vomiting. Table 2 summarizes the adverse reactions regardless of causality from the trial in patients with relapsed or refractory PTCL.

Table 1: Adverse Reactions Occurring in ≥ 10% of Patients with Relapsed or Refractory PTCL (NCI-CTC Grade 1-4)

Adverse Reactions	Percentage of Patients (%) (N=129)
	All Grades	Grade 3 or 4
All Adverse Reactions	97	61
Nausea	42	1
Fatigue	37	5
Pyrexia	35	2
Anemia	32	11
Vomiting	29	1
Constipation	23	1
Diarrhea	23	2
Dyspnea	22	6
Rash	20	1
Peripheral Edema	20	0
Cough	19	0
Thrombocytopenia	16	7
Pruritus	16	3
Chills	16	1
Increased Blood Lactate Dehydrogenase	16	2
Decreased Appetite	15	2
Headache	15	0
Infusion Site Pain	14	0
Hypokalemia	12	4
Prolonged QT	11	4
Abdominal pain	11	1
Hypotension	10	3
Phlebitis	10	1
Dizziness	10	0

 

Note: Adverse reactions are listed by order of incidence in the “All Grades” category first, then by incidence in “the Grade 3 or 4” category; Measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0

Serious Adverse Reactions

Sixty-one patients (47.3%) experienced serious adverse reactions while taking Beleodaq or within 30 days after their last dose of Beleodaq. The most common serious adverse reactions (> 2%) were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multi-organ failure.

One treatment-related death associated with hepatic failure was reported in the trial. One patient with baseline hyperuricemia and bulky disease experienced Grade 4 tumor lysis syndrome during the first cycle of treatment and died due to multi-organ failure. A treatment-related death from ventricular fibrillation was reported in another monotherapy clinical trial with Beleodaq. ECG analysis did not identify QTc prolongation.

Discontinuations Due To Adverse Reactions

Twenty-five patients (19.4%) discontinued treatment with Beleodaq due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment included anemia, febrile neutropenia, fatigue, and multi-organ failure.

Dosage Modifications Due To Adverse Reactions

In the trial, dosage adjustments due to adverse reactions occurred in 12% of Beleodaq-treated patients.

 

SRC: NLM .