DACOGEN SIDE EFFECTS

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

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

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