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Vidaza (Azacitidine Subcutaneous) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Overview

Adverse Reactions Described in Other Labeling Sections: anemia, neutropenia, thrombocytopenia, elevated serum creatinine, renal failure, renal tubular acidosis, hypokalemia, hepatic coma [see Warnings and Precautions (5.1, 5.2, 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].

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
     Anemia153 (69.5)59 (64.1)
     Anemia aggravated12 (5.5)5 (5.4)
     Febrile neutropenia36 (16.4)4 (4.3)
     Leukopenia106 (48.2)27 (29.3)
     Neutropenia71 (32.3)10 (10.9)
     Thrombocytopenia144 (65.5)42 (45.7)
Gastrointestinal disorders
     Abdominal tenderness26 (11.8)1 (1.1)
     Constipation74 (33.6)6 (6.5)
     Diarrhea80 (36.4)13 (14.1)
     Gingival bleeding21 (9.5)4 (4.3)
     Loose stools12 (5.5)0
     Mouth hemorrhage11 (5.0)1 (1.1)
     Nausea155 (70.5)16 (17.4)
     Stomatitis17 (7.7)0
     Vomiting119 (54.1)5 (5.4)
General disorders and administration site conditions
     Chest pain36 (16.4)5 (5.4)
     Injection site bruising31 (14.1)0
     Injection site erythema77 (35.0)0
     Injection site granuloma11 (5.0)0
     Injection site pain50 (22.7)0
     Injection site pigmentation changes11 (5.0)0
     Injection site pruritus15 (6.8)0
     Injection site reaction30 (13.6)0
     Injection site swelling11 (5.0)0
     Lethargy17 (7.7)2 (2.2)
     Malaise24 (10.9)1 (1.1)
      Pyrexia114 (51.8)28 (30.4)
Infections and infestations
     Nasopharyngitis32 (14.5)3 (3.3)
     Pneumonia24 (10.9)5 (5.4)
     Upper respiratory tract infection28 (12.7)4 (4.3)
Injury, poisoning, and procedural complications
     Post procedural hemorrhage13 (5.9)1 (1.1)
Metabolism and nutrition disorders
     Anorexia45 (20.5)6 (6.5)
Musculoskeletal and connective tissue disorders
     Arthralgia49 (22.3)3 (3.3)
     Chest wall pain11 (5.0)0
     Myalgia35 (15.9)2 (2.2)
Nervous system disorders
     Dizziness41 (18.6)5 (5.4)
     Headache48 (21.8)10 (10.9)
Psychiatric disorders
     Anxiety29 (13.2)3 (3.3)
     Insomnia24 (10.9)4 (4.3)
Respiratory, thoracic and mediastinal disorders
     Dyspnea64 (29.1)11 (12.0)
Skin and subcutaneous tissue disorders
     Dry skin11 (5.0)1 (1.1)
     Ecchymosis67 (30.5)14 (15.2)
     Erythema37 (16.8)4 (4.3)
     Rash31 (14.1)9 (9.8)
     Skin nodule11 (5.0)1 (1.1)
     Urticaria13 (5.9)1 (1.1)
Vascular disorders
     Hematoma19 (8.6)0
     Hypotension15 (6.8)2 (2.2)
     Petechiae52 (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
     Anemia90 (51.4)45 (44.1)24 (13.7)9 (8.8)
     Febrile neutropenia24 (13.7)10 (9.8)22 (12.6)7 (6.9)
     Leukopenia32 (18.3)2 (2.0)26 (14.9)1 (1.0)
     Neutropenia115 (65.7)29 (28.4)107 (61.1)22 (21.6)
     Thrombocytopenia122 (69.7)35 (34.3)102 (58.3)29 (28.4)
Gastrointestinal disorders
     Abdominal pain22 (12.6)7 (6.9)7 (4.0)0
     Constipation88 (50.3)8 (7.8)2 (1.1)0
     Dyspepsia10 (5.7)2 (2.0)00
     Nausea84 (48.0)12 (11.8)3 (1.7)0
     Vomiting47 (26.9)7 (6.9)00
General disorders and administration site conditions
     Fatigue42 (24.0)12 (11.8)6 (3.4)2 (2.0)
     Injection site bruising9 (5.1)000
     Injection site erythema75 (42.9)000
     Injection site hematoma11 (6.3)000
     Injection site induration9 (5.1)000
     Injection site pain33 (18.9)000
     Injection site rash10 (5.7)000
     Injection site reaction51 (29.1)01 (0.6)0
     Pyrexia53 (30.3)18 (17.6)8 (4.6)1 (1.0)
Infections and infestations
     Rhinitis10 (5.7)1 (1.0)00
     Upper respiratory tract infection16 (9.1)4 (3.9)3 (1.7)0
     Urinary tract infection15 (8.6)3 (2.9)3 (1.7)0
Investigations
     Weight decreased14 (8.0)01 (0.6)0
Metabolism and nutrition disorders
     Hypokalemia11 (6.3)3 (2.9)3 (1.7)3 (2.9)
Nervous system disorders
     Lethargy13 (7.4)2 (2.0)01 (1.0)
Psychiatric disorders
     Anxiety9 (5.1)1 (1.0)00
     Insomnia15 (8.6)3 (2.9)00
Renal and urinary disorders
     Hematuria11 (6.3)2 (2.0)4 (2.3)1 (1.0)
Respiratory, thoracic and mediastinal disorders
     Dyspnea26 (14.9)5 (4.9)6 (3.4)2 (2.0)
     Dyspnea exertional9 (5.1)1 (1.0)00
     Pharyngolaryngeal pain11 (6.3)3 (2.9)00
Skin and subcutaneous tissue disorders
     Erythema13 (7.4)3 (2.9)00
     Petechiae20 (11.4)4 (3.9)2 (1.1)0
     Pruritus21 (12.0)2 (2.0)00
     Rash18 (10.3)1 (1.0)00
Vascular disorders
     Hypertension15 (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

Adverse reactions identified from spontaneous reports have been similar to those reported during clinical trials with VIDAZA.



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: 2008-09-05

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