ONUREG SIDE EFFECTS
- Generic Name: azacitidine tablets
- Brand Name: Onureg
- Drug Class: Antineoplastics DNA Methylation Inhibitor
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Myelosuppression
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.
Acute Myeloid Leukemia
The safety of ONUREG was evaluated in QUAZAR. Patients received ONUREG 300 mg (N=236) or placebo (N=233) orally once daily on Days 1 through 14 of each 28-day cycle. Among patients who received ONUREG, 71% were exposed for 6 months or longer, and 49% were exposed for greater than one year. The median duration of exposure to ONUREG was 11.6 months (range: 0.5 to 74.3 months) and the median number of cycles was 12 (range: 1 to 82 cycles).
Serious adverse reactions occurred in 15% of patients who received ONUREG. Serious adverse reactions in ≥ 2% of patients who received ONUREG were pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG.
Permanent discontinuation of ONUREG due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ONUREG in > 1% of patients included nausea (2.1%), diarrhea (1.7%), and vomiting (1.3%). Interruptions of ONUREG due to an adverse reaction occurred in 35% of patients. Adverse reactions which required an interruption of ONUREG in > 5% of patients included neutropenia (20%), thrombocytopenia (8%), and nausea (6%).
Dose reductions of ONUREG due to an adverse reaction occurred in 14% of patients. Adverse reactions which required a dose reduction in > 1% of patients included neutropenia (6%), diarrhea (3.4%), thrombocytopenia (1.7%), and nausea (1.7%).
The most common (≥ 10%) adverse reactions were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, and pain in extremity.
Table 1 summarizes the adverse reactions in QUAZAR.
Table 1: Adverse Reactions (≥ 5%) in Patients with AML Who Received ONUREG with a Difference Between Arms of > 2% Compared to Placebo in QUAZARR
| Adverse Reaction | ONUREG (N=236) |
Placebo (N=233) |
||
| All Grades (%) | Grade 3 or 4 (%) | All Grades (%) | Grade 3 or 4 (%) | |
| Gastrointestinal disorders | ||||
| Nausea | 65 | 3 | 24 | < 1 |
| Vomiting | 60 | 3 | 10 | 0 |
| Diarrhea | 50 | 5 | 21 | 1 |
| Constipation | 39 | 1 | 24 | 0 |
| Abdominal paina | 22 | 2 | 13 | < 1 |
| General disorders and administration site conditions | ||||
| Fatigue / astheniab | 44 | 4 | 25 | 1 |
| Infections | ||||
| Pneumoniac | 27 | 9 | 17 | 5 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 14 | 1 | 10 | < 1 |
| Pain in extremity | 11 | < 1 | 5 | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 13 | 1 | 6 | 1 |
| Blood and lymphatic disorders | ||||
| Febrile neutropenia | 12 | 11 | 8 | 8 |
| Nervous system disorders | ||||
| Dizziness | 11 | 0 | 9 | 0 |
| aGrouped term includes abdominal pain, abdominal pain upper, abdominal discomfort, and gastrointestinal pain. bGrouped term includes fatigue and asthenia. cBroad scope term includes influenza, pneumonia, respiratory tract infection, respiratory tract infection viral, bronchopulmonary aspergillosis, lung infection, Staphylococcal infection, atypical pneumonia, lower respiratory tract infection, lung abscess, Pneumocystis jirovecii pneumonia, pneumonia bacterial, pneumonia fungal, Pseudomonas infection, hemoptysis, productive cough, pleural effusion, atelectasis, pleuritic pain, rales, Enterobacter test positive, and Hemophilus test positive. |
||||
Clinically relevant adverse reactions that did not meet criteria for inclusion in Table 2 were weight decreased (4%) in patients who received ONUREG.
Neutropenia, thrombocytopenia, and anemia of any grade occurred in 74%, 65%, and 25% of patients who received ONUREG. Table 2 summarizes select Grades 3 or 4 hematological laboratory abnormalities in QUAZAR.
Table 2: Selected Hematological Laboratory Abnormalities That Worsened from Baseline in Patients Who Received ONUREG in QUAZAR
| Laboratory Abnormality | ONUREG | Placebo | ||
| Baseline Grade 0-2 N | Post-Baseline Grade 3 or 4 n (%) | Baseline Grade 0-2 N | Post-Baseline Grade 3 or 4 n (%) | |
| Neutropenia | 223 | 109 (49) | 217 | 50 (23) |
| Thrombocytopenia | 222 | 46 (21) | 212 | 22 (10) |
| Anemia | 229 | 10 (4) | 223 | 7 (3) |
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of intravenous or subcutaneous azacitidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reaction
- Interstitial lung disease
- Tumor lysis syndrome
- Sweet’s syndrome (acute febrile neutrophilic dermatosis)
- Necrotizing fasciitis (including fatal cases)
- Differentiation syndrome
SRC: NLM .