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Vidaza (Azacitidine Subcutaneous) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The following adverse reactions are described in other labeling sections:

  • Anemia, neutropenia and thrombocytopenia [see Warnings and Precautions (5.1)]
  • Hepatic coma [see Warnings and Precautions (5.2)]
  • Elevated serum creatinine, renal failure, and renal tubular acidosis [see Warnings and Precautions (5.3)]
  • Most Commonly Occurring Adverse Reactions (SC or IV Route): nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia, ecchymosis. The most common adverse reactions by IV route also included petechiae, rigors, weakness and hypokalemia.

    Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (SC or IV Route):
    Discontinuation: leukopenia, thrombocytopenia, neutropenia.
    Dose Held: leukopenia, neutropenia, thrombocytopenia, pyrexia, pneumonia, febrile neutropenia.
    Dose Reduced: leukopenia, neutropenia, thrombocytopenia.

    Adverse Reactions in Clinical Trials

    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 data described below reflect exposure to VIDAZA in 443 MDS patients from 4 clinical studies. Study 1 was a supportive-care controlled trial (SC administration), Studies 2 and 3 were single arm studies (one with SC administration and one with IV administration), and Study 4 was an international randomized trial (SC administration) [see Clinical Studies (14)].

    In Studies 1, 2 and 3, a total of 268 patients were exposed to VIDAZA, including 116 exposed for 6 cycles (approximately 6 months) or more and 60 exposed for greater than 12 cycles (approximately one year). VIDAZA was studied primarily in supportive-care controlled and uncontrolled trials (n=150 and n=118, respectively). The population in the subcutaneous studies (n=220) was 23 to 92 years old (mean 66.4 years), 68% male, and 94% white, and had MDS or AML. The population in the IV study (n=48) was 35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients received average daily doses between 50 and 100 mg/m2.

    In Study 4, a total of 175 patients with higher-risk MDS (primarily RAEB and RAEB-T subtypes) were exposed to VIDAZA. Of these patients, 119 were exposed for 6 or more cycles, and 63 for at least 12 cycles. The mean age of this population was 68.1 years (ranging from 42 to 83 years), 74% were male, and 99% were white. Most patients received daily VIDAZA doses of 75 mg/m2.

    Table 1 presents adverse reactions occurring in at least 5% of patients treated with VIDAZA (SC) in Studies 1 and 2. It is important to note that duration of exposure was longer for the VIDAZA-treated group than for the observation group: patients received VIDAZA for a mean of 11.4 months while mean time in the observation arm was 6.1 months.

    Table 1: Most Frequently Observed Adverse Reactions (≥ 5.0% in All SC VIDAZA Treated Patients; Studies 1 and 2)
    Number (%) of Patients
    System Organ Class
         Preferred Term
    a
    All VIDAZA b
    (N=220)
    Observation c
    (N=92)

    a Multiple terms of the same preferred terms for a patient are only counted once within each treatment group.

    b Includes adverse reactions from all patients exposed to VIDAZA, including patients after crossing over from observations.

    c Includes adverse reactions from observation period only; excludes any adverse events after crossover to VIDAZA.

    Blood and lymphatic system disorders
         Anemia 153 (69.5) 59 (64.1)
         Anemia aggravated 12 (5.5) 5 (5.4)
         Febrile neutropenia 36 (16.4) 4 (4.3)
         Leukopenia 106 (48.2) 27 (29.3)
         Neutropenia 71 (32.3) 10 (10.9)
         Thrombocytopenia 144 (65.5) 42 (45.7)
    Gastrointestinal disorders
         Abdominal tenderness 26 (11.8) 1 (1.1)
         Constipation 74 (33.6) 6 (6.5)
         Diarrhea 80 (36.4) 13 (14.1)
         Gingival bleeding 21 (9.5) 4 (4.3)
         Loose stools 12 (5.5) 0
         Mouth hemorrhage 11 (5.0) 1 (1.1)
         Nausea 155 (70.5) 16 (17.4)
         Stomatitis 17 (7.7) 0
         Vomiting 119 (54.1) 5 (5.4)
    General disorders and administration site conditions
         Chest pain 36 (16.4) 5 (5.4)
         Injection site bruising 31 (14.1) 0
         Injection site erythema 77 (35.0) 0
         Injection site granuloma 11 (5.0) 0
         Injection site pain 50 (22.7) 0
         Injection site pigmentation changes 11 (5.0) 0
         Injection site pruritus 15 (6.8) 0
         Injection site reaction 30 (13.6) 0
         Injection site swelling 11 (5.0) 0
         Lethargy 17 (7.7) 2 (2.2)
         Malaise 24 (10.9) 1 (1.1)
         Pyrexia 114 (51.8) 28 (30.4)
    Infections and infestations
         Nasopharyngitis 32 (14.5) 3 (3.3)
         Pneumonia 24 (10.9) 5 (5.4)
         Upper respiratory tract infection 28 (12.7) 4 (4.3)
    Injury, poisoning, and procedural complications
         Post procedural hemorrhage 13 (5.9) 1 (1.1)
    Metabolism and nutrition disorders
         Anorexia 45 (20.5) 6 (6.5)
    Musculoskeletal and connective tissue disorders
         Arthralgia 49 (22.3) 3 (3.3)
         Chest wall pain 11 (5.0) 0
         Myalgia 35 (15.9) 2 (2.2)
    Nervous system disorders
         Dizziness 41 (18.6) 5 (5.4)
         Headache 48 (21.8) 10 (10.9)
    Psychiatric disorders
         Anxiety 29 (13.2) 3 (3.3)
         Insomnia 24 (10.9) 4 (4.3)
    Respiratory, thoracic and mediastinal disorders
         Dyspnea 64 (29.1) 11 (12.0)
    Skin and subcutaneous tissue disorders
         Dry skin 11 (5.0) 1 (1.1)
         Ecchymosis 67 (30.5) 14 (15.2)
         Erythema 37 (16.8) 4 (4.3)
         Rash 31 (14.1) 9 (9.8)
         Skin nodule 11 (5.0) 1 (1.1)
         Urticaria 13 (5.9) 1 (1.1)
    Vascular disorders
         Hematoma 19 (8.6) 0
         Hypotension 15 (6.8) 2 (2.2)
         Petechiae 52 (23.6) 8 (8.7)

    Table 2 presents adverse reactions occurring in at least 5% of patients treated with VIDAZA in Study 4. Similar to Studies 1 and 2 described above, duration of exposure to treatment with VIDAZA was longer (mean 12.2 months) compared with best supportive care (mean 7.5 months).

    Table 2: Most Frequently Observed Adverse Reactions (≥ 5.0% in the VIDAZA Treated Patients and the Percentage with NCI CTC Grade 3/4 Reactions; Study 4)
    Number (%) of Patients
    Any Grade Grade 3/4
    System Organ Class
         Preferred Term
    a
    VIDAZA
    (N=175)
    Best Supportive Care Only
    (N=102)
    VIDAZA
    (N=175)
    Best Supportive Care Only
    (N=102)

    a Multiple reports of the same preferred term from a patient were only counted once within each treatment.

    Blood and lymphatic system disorders
         Anemia 90 (51.4) 45 (44.1) 24 (13.7) 9 (8.8)
         Febrile neutropenia 24 (13.7) 10 (9.8) 22 (12.6) 7 (6.9)
         Leukopenia 32 (18.3) 2 (2.0) 26 (14.9) 1 (1.0)
         Neutropenia 115 (65.7) 29 (28.4) 107 (61.1) 22 (21.6)
         Thrombocytopenia 122 (69.7) 35 (34.3) 102 (58.3) 29 (28.4)
    Gastrointestinal disorders
         Abdominal pain 22 (12.6) 7 (6.9) 7 (4.0) 0
         Constipation 88 (50.3) 8 (7.8) 2 (1.1) 0
         Dyspepsia 10 (5.7) 2 (2.0) 0 0
         Nausea 84 (48.0) 12 (11.8) 3 (1.7) 0
         Vomiting 47 (26.9) 7 (6.9) 0 0
    General disorders and administration site conditions
         Fatigue 42 (24.0) 12 (11.8) 6 (3.4) 2 (2.0)
         Injection site bruising 9 (5.1) 0 0 0
         Injection site erythema 75 (42.9) 0 0 0
         Injection site hematoma 11 (6.3) 0 0 0
         Injection site induration 9 (5.1) 0 0 0
         Injection site pain 33 (18.9) 0 0 0
         Injection site rash 10 (5.7) 0 0 0
         Injection site reaction 51 (29.1) 0 1 (0.6) 0
         Pyrexia 53 (30.3) 18 (17.6) 8 (4.6) 1 (1.0)
    Infections and infestations
         Rhinitis 10 (5.7) 1 (1.0) 0 0
         Upper respiratory tract infection 16 (9.1) 4 (3.9) 3 (1.7) 0
         Urinary tract infection 15 (8.6) 3 (2.9) 3 (1.7) 0
    Investigations
         Weight decreased 14 (8.0) 0 1 (0.6) 0
    Metabolism and nutrition disorders
         Hypokalemia 11 (6.3) 3 (2.9) 3 (1.7) 3 (2.9)
    Nervous system disorders
         Lethargy 13 (7.4) 2 (2.0) 0 1 (1.0)
    Psychiatric disorders
         Anxiety 9 (5.1) 1 (1.0) 0 0
         Insomnia 15 (8.6) 3 (2.9) 0 0
    Renal and urinary disorders
         Hematuria 11 (6.3) 2 (2.0) 4 (2.3) 1 (1.0)
    Respiratory, thoracic and mediastinal disorders
         Dyspnea 26 (14.9) 5 (4.9) 6 (3.4) 2 (2.0)
         Dyspnea exertional 9 (5.1) 1 (1.0) 0 0
         Pharyngolaryngeal pain 11 (6.3) 3 (2.9) 0 0
    Skin and subcutaneous tissue disorders
         Erythema 13 (7.4) 3 (2.9) 0 0
         Petechiae 20 (11.4) 4 (3.9) 2 (1.1) 0
         Pruritus 21 (12.0) 2 (2.0) 0 0
         Rash 18 (10.3) 1 (1.0) 0 0
    Vascular disorders
         Hypertension 15 (8.6) 4 (3.9) 2 (1.1) 2 (2.0)

    In Studies 1, 2 and 4 with SC administration of VIDAZA, adverse reactions of neutropenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, constipation, and injection site erythema/reaction tended to increase in incidence with higher doses of VIDAZA. Adverse reactions that tended to be more pronounced during the first 1 to 2 cycles of SC treatment compared with later cycles included thrombocytopenia, neutropenia, anemia, nausea, vomiting, injection site erythema/pain/bruising/reaction, constipation, petechiae, dizziness, anxiety, hypokalemia, and insomnia. There did not appear to be any adverse reactions that increased in frequency over the course of treatment.

    Overall, adverse reactions were qualitatively similar between the IV and SC studies. Adverse reactions that appeared to be specifically associated with the IV route of administration included infusion site reactions (e.g. erythema or pain) and catheter site reactions (e.g. infection, erythema, or hemorrhage).

    In clinical studies of either SC or IV VIDAZA, the following serious adverse reactions occurring at a rate of < 5% (and not described in Tables 1 or 2) were reported:

    Blood and lymphatic system disorders: agranulocytosis, bone marrow failure, pancytopenia splenomegaly.

    Cardiac disorders: atrial fibrillation, cardiac failure, cardiac failure congestive, cardio-respiratory arrest, congestive cardiomyopathy.

    Eye disorders: eye hemorrhage

    Gastrointestinal disorders: diverticulitis, gastrointestinal hemorrhage, melena, perirectal abscess.

    General disorders and administration site conditions: catheter site hemorrhage, general physical health deterioration, systemic inflammatory response syndrome.

    Hepatobiliary disorders: cholecystitis.

    Immune system disorders: anaphylactic shock, hypersensitivity.

    Infections and infestations: abscess limb, bacterial infection, cellulitis, blastomycosis, injection site infection, Klebsiella sepsis, neutropenic sepsis, pharyngitis streptococcal, pneumonia Klebsiella, sepsis, septic shock, Staphylococcal bacteremia, Staphylococcal infection, toxoplasmosis.

    Metabolism and nutrition disorders: dehydration.

    Musculoskeletal and connective tissue disorders: bone pain aggravated, muscle weakness, neck pain.

    Neoplasms benign, malignant and unspecified: leukemia cutis.

    Nervous system disorders: cerebral hemorrhage, convulsions, intracranial hemorrhage.

    Renal and urinary disorders: loin pain, renal failure.

    Respiratory, thoracic and mediastinal disorders: hemoptysis, lung infiltration, pneumonitis, respiratory distress.

    Skin and subcutaneous tissue disorders: pyoderma gangrenosum, rash pruritic, skin induration.

    Surgical and medical procedures: cholecystectomy.

    Vascular disorders: orthostatic hypotension.

    Postmarketing Experience

    The following adverse reactions have been identified during postmarketing use of VIDAZA. 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.

    • – Interstitial lung disease
    • – Tumor lysis syndrome
    • – Injection site necrosis
    • – Sweet’s syndrome (acute febrile neutrophilic dermatosis)


    REPORTS OF SUSPECTED VIDAZA SIDE EFFECTS / ADVERSE REACTIONS

    Below is a sample of reports where side effects / adverse reactions may be related to Vidaza. The information is not vetted and should not be considered as verified clinical evidence.

    Possible Vidaza side effects / adverse reactions in 69 year old male

    Reported by a physician from United States on 2011-10-03

    Patient: 69 year old male weighing 59.0 kg (129.8 pounds)

    Reactions: Malaise, Injection Site Erythema, Pyrexia, Septic Shock, Decreased Appetite

    Adverse event resulted in: death

    Suspect drug(s):
    Vidaza

    Other drugs received by patient: Immune Globulin Intravenous (Human); Allopurinol; Omeptorol; Magnesium Sulfate; Urso 250; Meropenem; Levofloxacin; Itraconazole; Myonal



    Possible Vidaza side effects / adverse reactions in 79 year old male

    Reported by a physician from Germany on 2011-10-03

    Patient: 79 year old male weighing 78.0 kg (171.6 pounds)

    Reactions: Sepsis

    Adverse event resulted in: life threatening event

    Suspect drug(s):
    Vidaza
        Start date: 2011-09-13

    Idarubicin HCL
        Start date: 2011-09-13

    Etoposide
        Start date: 2011-09-13



    Possible Vidaza side effects / adverse reactions in 77 year old male

    Reported by a physician from Germany on 2011-10-04

    Patient: 77 year old male weighing 80.0 kg (176.0 pounds)

    Reactions: Chills

    Suspect drug(s):
    Vidaza
        Start date: 2011-06-27
        End date: 2011-07-01

    Tazobac
        Indication: Infection Prophylaxis
        Start date: 2011-09-15
        End date: 2011-09-16

    Cytarabine
        Start date: 2011-09-14
        End date: 2011-09-16

    Etoposide

    Lenograstim
        Start date: 2011-03-23
        End date: 2011-01-01

    Piperacillin
        Dosage: 12 gram
        Indication: Infection Prophylaxis
        Start date: 2011-09-15
        End date: 2011-09-16

    Vidaza
        Start date: 2011-05-28
        End date: 2011-06-01

    Idarubicin HCL

    Other drugs received by patient: Levofloxacin



    See index of all Vidaza side effect reports >>

    Drug label data at the top of this Page last updated: 2014-01-17

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