DACOGEN SIDE EFFECTS
- Generic Name: decitabine injection
- Brand Name: Dacogen
- Drug Class: How Do Antineoplastic DNA Methylation Inhibitors Work? How Do Antineoplastic DNA Methylation Inhibitors Work?
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.
The safety of DACOGEN was studied in 3 single-arm studies (N = 66, N = 98, N = 99) and 1 controlled supportive care study (N = 83 DACOGEN, N = 81 supportive care). The data described below reflect exposure to DACOGEN in 83 patients in the MDS trial. In the trial, patients received 15 mg/m² intravenously every 8 hours for 3 days every 6 weeks. The median number of DACOGEN cycles was 3 (range 0 to 9).
Most Common Adverse Reactions: neutropenia, thrombocytopenia, anemia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.
Adverse Reactions Most Frequently (≥ 1%) Resulting in Clinical Intervention and or Dose Modification in the Controlled Supportive Care Study in the DACOGEN Arm:
- Discontinuation: thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardio-respiratory arrest, increased blood bilirubin, intracranial hemorrhage, abnormal liver function tests.
- Dose Delayed: neutropenia, pulmonary edema, atrial fibrillation, central line infection, febrile neutropenia.
- Dose Reduced: neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, pharyngitis.
Table 1 presents all adverse reactions occurring in at least 5% of patients in the DACOGEN group and at a rate greater than supportive care.
Table 1: Adverse Reactions Reported in ≥ 5% of Patients in the DACOGEN Group andat a Rate Greater than Supportive Care in the Controlled Trial in MDS
| DACOGEN N = 83 (%) |
Supportive Care N = 81 (%) |
|
| Blood and lymphatic system disorders | ||
| Neutropenia | 75 (90) | 58 (72) |
| Thrombocytopenia | 74 (89) | 64 (79) |
| Anemia NOS | 68 (82) | 60 (74) |
| Febrile neutropenia | 24 (29) | 5 (6) |
| Leukopenia NOS | 23(28) | 11 (14) |
| Lymphadenopathy | 10(12) | 6 (7) |
| Thrombocythemia | 4 (5) | 1 (1) |
| Cardiac disorders | ||
| Pulmonary edema NOS | 5 (6) | 0 (0) |
| Eye disorders | ||
| Vision blurred | 5 (6) | 0 (0) |
| Gastrointestinal disorders | ||
| Nausea | 35 (42) | 13 (16) |
| Constipation | 29 (35) | 11 (14) |
| Diarrhea NOS | 28 (34) | 13 (16) |
| Vomiting NOS | 21 (25) | 7 (9) |
| Abdominal pain NOS | 12 (14) | 5 (6) |
| Oral mucosal petechiae | 11 (13) | 4 (5) |
| Stomatitis | 10 (12) | 5 (6) |
| Dyspepsia | 10 (12) | 1 (1) |
| Ascites | 8 (10) | 2 (2) |
| Gingival bleeding | 7 (8) | 5 (6) |
| Hemorrhoids | 7 (8) | 3 (4) |
| Loose stools | 6 (7) | 3 (4) |
| Tongue ulceration | 6 (7) | 2 (2) |
| Dysphagia | 5 (6) | 2 (2) |
| Oral soft tissue disorder NOS | 5 (6) | 1 (1) |
| Lip ulceration | 4 (5) | 3 (4) |
| Abdominal distension | 4 (5) | 1 (1) |
| Abdominal pain upper | 4 (5) | 1 (1) |
| Gastro-esophageal reflux disease | 4 (5) | 0 (0) |
| Glossodynia | 4 (5) | 0 (0) |
| General disorders and administrative site disorders | ||
| Pyrexia | 44 (53) | 23 (28) |
| Edema peripheral | 21 (25) | 13 (16) |
| Rigors | 18 (22) | 14 (17) |
| Edema NOS | 15 (18) | 5 (6) |
| Pain NOS | 11 (13) | 5 (6) |
| Lethargy | 10 (12) | 3 (4) |
| Tenderness NOS | 9 (11) | 0 (0) |
| Fall | 7 (8) | 3 (4) |
| Chest discomfort | 6 (7) | 3 (4) |
| Intermittent pyrexia | 5 (6) | 3 (4) |
| Malaise | 4 (5) | 1 (1) |
| Crepitations NOS | 4 (5) | 1 (1) |
| Catheter site erythema | 4 (5) | 1 (1) |
| Catheter site pain | 4 (5) | 0 (0) |
| Injection site swelling | 4 (5) | 0 (0) |
| Hepatobiliary disorders | ||
| Hyperbilirubinemia | 12 (14) | 4 (5) |
| Infections and infestations | ||
| Pneumonia NOS | 18 (22) | 11(14) |
| Cellulitis | 10 (12) | 6 (7) |
| Candidal infection NOS | 8 (10) | 1 (1) |
| Catheter related infection | 7 (8) | 0 (0) |
| Urinary tract infection NOS | 6 (7) | 1 (1) |
| Staphylococcal infection | 6 (7) | 0 (0) |
| Oral candidiasis | 5 (6) | 2 (2) |
| Sinusitis NOS | 4 (5) | 2 (2) |
| Bacteremia | 4 (5) | 0 (0) |
| Injury, poisoning and procedural complications | ||
| Transfusion reaction | 6 (7) | 3 (4) |
| Abrasion NOS | 4 (5) | 1 (1) |
| Investigations | ||
| Cardiac murmur NOS | 13 (16) | 9 (11) |
| Blood alkaline phosphatase NOS increased | 9 (11) | 7 (9) |
| Aspartate aminotransferase increased | 8 (10) | 7 (9) |
| Blood urea increased | 8 (10) | 1 (1) |
| Blood lactate dehydrogenase increased | 7 (8) | 5 (6) |
| Blood albumin decreased | 6 (7) | 0 (0) |
| Blood bicarbonate increased | 5 (6) | 1 (1) |
| Blood chloride decreased | 5 (6) | 1 (1) |
| Protein total decreased | 4 (5) | 3 (4) |
| Blood bicarbonate decreased | 4 (5) | 1 (1) |
| Blood bilirubin decreased | 4 (5) | 1 (1) |
| Metabolism and nutrition disorters | ||
| Hyperglycemia NOS | 27 (33) | 16 (20) |
| Hypoalbuminemia | 20 (24) | 14 (17) |
| Hypomagnesemia | 20 (24) | 6 (7) |
| Hypokalemia | 18 (22) | 10 (12) |
| Hyponatremia | 16 (19) | 13 (16) |
| Appetite decreased NOS | 13 (16) | 12 (15) |
| Anorexia | 13 (16) | 8 (10) |
| Hyperkalemia | 11 (13) | 3 (4) |
| Dehydration | 5 (6) | 4 (5) |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 17 (20) | 8 (10) |
| Pain in limb | 16 (19) | 8 (10) |
| Back pain | 14 (17) | 5 (6) |
| Chest wall pain | 6 (7) | 1 (1) |
| Musculoskeletal discomfort | 5 (6) | 0 (0) |
| Myalgia | 4 (5) | 1 (1) |
| Nervous system disorders | ||
| Headache | 23(28) | 11(14) |
| Dizziness | 15 (18) | 10 (12) |
| Hypoesthesia | 9 (11) | 1 (1) |
| Psychiatric disorders | ||
| Insomnia | 23(28) | 11 (14) |
| Confusional state | 10(12) | 3 (4) |
| Anxiety | 9 (11) | 8 (10) |
| Renal and urinary disorders | ||
| Dysuria | 5 (6) | 3 (4) |
| Urinary frequency | 4 (5) | 1 (1) |
| Respiratory, thoracic and Mediastinal disorders | ||
| Cough | 33 (40) | 25 (31) |
| Pharyngitis | 13 (16) | 6 (7) |
| Crackles lung | 12 (14) | 1 (1) |
| Breath sounds decreased | 8 (10) | 7 (9) |
| Hypoxia | 8 (10) | 4 (5) |
| Rales | 7 (8) | 2 (2) |
| Postnasal drip | 4 (5) | 2 (2) |
| Skin and subcutaneous tissue disorders | ||
| Ecchymosis | 18 (22) | 12 (15) |
| Rash NOS | 16 (19) | 7 (9) |
| Erythema | 12 (14) | 5 (6) |
| Skin lesion NOS | 9 (11) | 3 (4) |
| Pruritis | 9 (11) | 2 (2) |
| Alopecia | 7 (8) | 1 (1) |
| Urticaria NOS | 5 (6) | 1 (1) |
| Swelling face | 5 (6) | 0 (0) |
| Vascular disorders | ||
| Petechiae | 32 (39) | 13 (16) |
| Pallor | 19 (23) | 10 (12) |
| Hypotension NOS | 5 (6) | 4 (5) |
| Hematoma NOS | 4 (5) | 3 (4) |
In a single-arm MDS study (N=99), DACOGEN was dosed at 20 mg/m² intravenously, infused over one hour daily, for 5 consecutive days of a 4-week cycle. Table 2 presents all adverse reactions occurring in at least 5% of patients.
Table 2: Adverse Reactions Reported in ≥ 5% of Patients in a Single-arm Study1
| DACOGEN N = 99 (%) |
|
| Blood and lymphatic system disorders | |
| Anemia | 31 (31) |
| Febrile neutropenia | 20 (20) |
| Leukopenia | 6 (6) |
| Neutropenia | 38 (38) |
| Pancytopenia | 5 (5) |
| Thrombocythemia | 5 (5) |
| Thrombocytopenia | 27 (27) |
| Cardiac disorders | |
| Cardiac failure congestive | 5 (5) |
| Tachycardia | 8 (8) |
| Ear and labyrinth disorders | |
| Ear pain | 6 (6) |
| Gastrointestinal disorders | |
| Abdominal pain | 14 (14) |
| Abdominal pain upper | 6(6) |
| Constipation | 30 (30) |
| Diarrhea | 28 (28) |
| Dyspepsia | 10 (10) |
| Dysphagia | 5 (5) |
| Gastro-esophageal reflux disease | 5 (5) |
| Nausea | 40 (40) |
| Oral pain | 5 (5) |
| Stomatitis | 11 (11) |
| Toothache | 6 (6) |
| Vomiting | 16 (16) |
| General disorders and administration site conditions | |
| Asthenia | 15 (15) |
| Chest pain | 6 (6) |
| Chills | 16 (16) |
| Fatigue | 46 (46) |
| Mucosal inflammation | 9 (9) |
| Edema | 5 (5) |
| Edema peripheral | 27 (27) |
| Pain | 5 (5) |
| Pyrexia | 36 (36) |
| Infections and infestations | |
| Cellulitis | 9 (9) |
| Oral candidiasis | 6 (6) |
| Pneumonia | 20 (20) |
| Sinusitis | 6 (6) |
| Staphylococcal bacteremia | 8 (8) |
| Tooth abscess | 5 (5) |
| Upper respiratory tract infection | 10 (10) |
| Urinary tract infection | 7 (7) |
| Injury, poisoning and procedural complications | |
| Contusion | 9 (9) |
| Investigations | |
| Blood bilirubin increased | 6 (6) |
| Breath sounds abnormal | 5 (5) |
| Weight decreased | 9 (9) |
| Metabolism and nutrition disorders | |
| Anorexia | 23 (23) |
| Decreased appetite | 8 (8) |
| Dehydration | 8 (8) |
| Hyperglycemia | 6 (6) |
| Hypokalemia | 12 (12) |
| Hypomagnesemia | 5 (5) |
| Musculoskeletal and connective tissue disorders | |
| Arthralgia | 17 (17) |
| Back pain | 18 (18) |
| Bone pain | 6 (6) |
| Muscle spasms | 7 (7) |
| Muscular weakness | 5 (5) |
| Musculoskeletal pain | 5 (5) |
| Myalgia | 9 (9) |
| Pain in extremity | 18 (18) |
| Nervous system disorders | |
| Dizziness | 21 (21) |
| Headache | 23 (23) |
| Psychiatric disorders | |
| Anxiety | 9 (9) |
| Confusional state | 8 (8) |
| Depression | 9 (9) |
| Insomnia | 14 (14) |
| Respiratory, thoracic and mediastinal disorders | |
| Cough | 27 (27) |
| Dyspnea | 29 (29) |
| Epistaxis | 13 (13) |
| Pharyngolaryngeal pain | 8 (8) |
| Pleural effusion | 5 (5) |
| Sinus congestion | 5 (5) |
| Skin and subcutaneous tissue disorders | |
| Dry skin | 8 (8) |
| Ecchymosis | 9 (9) |
| Erythema | 5 (5) |
| Night sweats | 5 (5) |
| Petechiae | 12 (12) |
| Pruritus | 9 (9) |
| Rash | 11 (11) |
| Skin lesion | 5 (5) |
| Vascular disorders | |
| Hypertension | 6 (6) |
| Hypotension | 11 (11) |
| 1 In this single arm study, investigators reported adverse events based on clinical signs and symptoms rather than predefined laboratory abnormalities. Thus, not all laboratory abnormalities were recorded as adverse events. | |
No overall difference in safety was detected between patients > 65 years of age and younger patients in these MDS trials. No significant differences in safety were detected between males and females. Patients with renal or hepatic dysfunction were not studied. Insufficient numbers of non-White patients were available to draw conclusions in these clinical trials.
Serious adverse reactions that occurred in patients receiving DACOGEN not previously reported in Tables 1 and 2 include:
- Allergic Reaction: hypersensitivity (anaphylactic reaction).
- Blood and Lymphatic System Disorders: myelosuppression, splenomegaly.
- Cardiac Disorders: myocardial infarction, cardio-respiratory arrest, cardiomyopathy, atrial fibrillation, supraventricular tachycardia.
- Gastrointestinal Disorders: gingival pain, upper gastrointestinal hemorrhage.
- General Disorders and Administrative Site Conditions: chest pain, catheter site hemorrhage.
- Hepatobiliary Disorders: cholecystitis.
- Infections and Infestations: fungal infection, sepsis, bronchopulmonary aspergillosis, peridiverticular abscess, respiratory tract infection, pseudomonal lung infection, Mycobacterium avium complex infection.
- Injury, Poisoning and Procedural Complications: post procedural pain, post procedural hemorrhage.
- Nervous System Disorders: intracranial hemorrhage.
- Psychiatric Disorders: mental status changes.
- Renal and Urinary Disorders: renal failure, urethral hemorrhage.
- Respiratory, Thoracic and Mediastinal Disorders: hemoptysis, lung infiltration, pulmonary embolism, respiratory arrest, pulmonary mass.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of DACOGEN. 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.
- Sweet’s syndrome (acute febrile neutrophilic dermatosis)
- Differentiation syndrome
SRC: NLM .