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Clolar (Clofarabine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:

  • Severe Bone Marrow Suppression [see Warnings and Precautions ]
  • Serious Infections [see Warnings and Precautions]
  • Hyperuricemia (Tumor Lysis) [see Warnings and Precautions ]
  • Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome [see Warnings and Precautions ]
  • Venous Occlusive Disease of the Liver [see Warnings and Precautions ]
  • Hepatotoxicity [see Warnings and Precautions ]
  • Renal Toxicity [see Warnings and Precautions ]

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 data described below reflect exposure to Clolar in 115 pediatric patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL) (70 patients) or Acute Myelogenous Leukemia (AML) (45 patients).

In total, 115 pediatric patients treated in clinical trials received the recommended dose of Clolar 52 mg/m2 daily × 5. The median number of cycles was 2. The median cumulative amount of Clolar received by pediatric patients during all cycles was 540 mg.

The most common adverse reactions occurring in 10% or more of patients treated with Clolar are: nausea, vomiting, diarrhea, febrile neutropenia, headache, rash, pruritus, pyrexia, fatigue, palmar-plantar erythrodysesthesia syndrome, anxiety, flushing, and mucosal inflammation.

Table 1 lists adverse reactions by System Organ Class, including severe or life-threatening (NCI CTC Grade 3 or Grade 4), reported in ≥ 5% of the 115 patients in the 52 mg/m2/day dose group (pooled analysis of pediatric patients with ALL and AML). More detailed information and follow-up of certain events is given below.

Table 1: Most Commonly Reported (≥ 5% Overall) Adverse Reactions by System Organ Class (N=115 pooled analysis)
Worst NCI Common Terminology Criteria Grade 1
ALL/AML (N=115) 3 4 5
System Organ Class Preferred Term N % N % N % N %
Blood and Lymphatic System Disorders Febrile neutropenia 63 54.8 59 51.3 3 2.6 . .
Neutropenia 11 9.6 3 2.6 8 7.0 . .
Cardiac Disorders Pericardial effusion 9 7.8 . . 1 0.9 . .
Tachycardia 40 34.8 6 5.2 . . . .
Gastrointestinal Disorders Abdominal pain 40 34.8 8 7.0 . . . .
Abdominal pain upper 9 7.8 1 0.9 . . . .
Diarrhea 64 55.7 14 12.2 . . . .
Gingival or mouth bleeding 20 17.4 8 7.0 1 0.9 . .
Nausea 84 73.0 16 13.9 1 0.9 . .
Oral mucosal petechiae 6 5.2 4 3.5 . . . .
Proctalgia 9 7.8 2 1.7 . . . .
Stomatitis 8 7.0 1 0.9 . . . .
Vomiting 90 78.3 9 7.8 1 0.9 . .
General Disorders and Administration Site Conditions Asthenia 12 10.4 1 0.9 1 0.9 . .
Chills 39 33.9 3 2.6 . . . .
Fatigue 39 33.9 3 2.6 2 1.7 . .
Irritability 11 9.6 1 0.9 . . . .
Mucosal inflammation 18 15.7 2 1.7 . . . .
Edema 14 12.2 2 1.7 . . . .
Pain 17 14.8 7 6.1 1 0.9 . .
Pyrexia 45 39.1 16 13.9 . . . .
Hepatobiliary Disorder Jaundice 9 7.8 2 1.7 . . . .
Infections and Infestations Bacteremia 10 8.7 10 8.7 . . . .
Candidiasis 8 7.0 1 0.9 . . . .
Catheter related infection 14 12.2 13 11.3 . . . .
Cellulitis 9 7.8 7 6.1 . . . .
Clostridium colitis 8 7.0 6 5.2 . . . .
Herpes simplex 11 9.6 6 5.2 . . . .
Herpes zoster 8 7.0 6 5.2 . . . .
Oral candidiasis 13 11.3 2 1.7 . . . .
Pneumonia 11 9.6 6 5.2 1 0.9 1 0.9
Sepsis, including septic shock 19 16.5 6 5.2 4 3.5 9 7.8
Staphylococcal bacteremia 7 6.1 5 4.4 1 0.9 . .
Staphylococcal sepsis 6 5.2 5 4.4 1 0.9 . .
Upper respiratory tract infection 6 5.2 1 0.9 . . . .
Metabolism and Nutrition Disorders Anorexia 34 29.6 6 5.2 8 7.0 . .
Musculoskeletal and Connective Tissue Disorders Arthralgia 10 8.7 3 2.6 . . . .
Back pain 12 10.4 3 2.6 . . . .
Bone pain 11 9.6 3 2.6 . . . .
Myalgia 16 13.9 . . . . . .
Pain in extremity 34 29.6 6 5.2 . . . .
Neoplasms Benign, Malignant and Unspecified (incl. cysts and polyps) Tumor lysis syndrome 7 6.1 7 6.1 . . . .
Nervous System Disorders Headache 49 42.6 6 5.2 . . . .
Lethargy 12 10.4 1 0.9 . . . .
Somnolence 11 9.6 1 0.9 . . . .
Psychiatric Disorders Agitation 6 5.2 1 0.9 . . . .
Anxiety 24 20.9 2 1.7 . . . .
Renal and Urinary Disorders Hematuria 15 13.0 2 1.7 . . . .
Respiratory, Thoracic and Mediastinal Disorders Dyspnea 15 13.0 6 5.2 2 1.7 . .
Epistaxis 31 27.0 15 13.0 . . . .
Pleural effusion 14 12.2 4 3.5 2 1.7 . .
Respiratory distress 12 10.4 5 4.4 4 3.5 1 0.9
Tachypnea 10 8.7 4 3.5 1 0.9 . .
Skin and Subcutaneous Tissue Disorders Erythema 13 11.3 . . . . . .
Palmar-plantar erythrodysesthesia syndrome 18 15.7 8 7.0 . . . .
Petechiae 30 26.1 7 6.1 . . . .
Pruritus 49 42.6 1 0.9 . . . .
Rash 44 38.3 8 7.0 . . . .
Rash pruritic 9 7.8 . . . . . .
Vascular Disorders Flushing 22 19.1 . . . . . .
Hypertension 15 13.0 6 5.2 . . . .
Hypotension 33 28.7 13 11.3 9 7.8 . .

1 Patients with more than one preferred term within a SOC are counted only once in the SOC totals. Patients with more than one occurrence of the same preferred term are counted only once within that term and at the highest severity grade.

The following less common adverse reactions have been reported in 1–4% of the 115 pediatric patients with ALL or AML:

Gastrointestinal Disorders: cecitis, pancreatitis

Hepatobiliary Disorders: hyperbilirubinemia

Immune System Disorders: hypersensitivity

Infections and Infestations: bacterial infection, Enterococcal bacteremia, Escherichia bacteremia, Escherichia sepsis, fungal infection, fungal sepsis, gastroenteritis adenovirus, infection, influenza, parainfluenza virus infection, pneumonia fungal, pneumonia primary atypical, Respiratory syncytial virus infection, sinusitis, staphylococcal infection

Investigations: blood creatinine increased

Psychiatric Disorders: mental status change

Respiratory, Thoracic and Mediastinal Disorder: pulmonary edema

Table 2 lists the incidence of treatment-emergent laboratory abnormalities after Clolar administration at 52 mg/m2 among pediatric patients with ALL and AML (N=115).

Table 2: Incidence of Treatment-Emergent Laboratory Abnormalities after Clolar Administration
Parameter Any Grade Grade 3 or higher
Anemia (N=114) 95 (83.3%) 86 (75.4%)
Leukopenia (N=114) 100 (87.7%) 100 (87.7%)
Lymphopenia (N=113) 93 (82.3%) 93 (82.3%)
Neutropenia (N=113) 72 (63.7%) 72 (63.7%)
Thrombocytopenia (N=114) 92 (80.7%) 91 (79.8%)
Elevated Creatinine (N=115) 57 (49.5%) 9 (7.8%)
Elevated SGOT (N=100) 74 (74.0%) 36 (36.0%)
Elevated SGPT (N=113) 91 (80.5%) 49 (43.4%)
Elevated Total Bilirubin (N=114) 51 (44.7%) 15 (13.2%)

Post-marketing Experience

The following adverse reactions have been identified during post-approval use of Clolar. 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. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal connection to Clolar.

  • Gastrointestinal disorders: Gastrointestinal hemorrhage including fatalities.
  • Skin and subcutaneous tissue disorders: Occurrences of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients who were receiving or had recently been treated with Clolar and other medications (e.g., allopurinol or antibiotics) known to cause these syndromes. Other exfoliative conditions have also been reported.


REPORTS OF SUSPECTED CLOLAR SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Clolar side effects / adverse reactions in 3 year old male

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

Patient: 3 year old male

Reactions: Acute Lymphocytic Leukaemia, Drug Ineffective

Adverse event resulted in: death

Suspect drug(s):
Etoposide
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia

Cyclophosphamide
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia

Clolar
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia



Possible Clolar side effects / adverse reactions in 7 year old female

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

Patient: 7 year old female

Reactions: Acute Lymphocytic Leukaemia, Disease Recurrence, Neoplasm Progression, Aplasia

Adverse event resulted in: death

Suspect drug(s):
Clolar
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia

Cyclophosphamide
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia

Etoposide
    Dosage: unk
    Indication: Acute Lymphocytic Leukaemia



Possible Clolar side effects / adverse reactions in 11 year old female

Reported by a physician from Colombia on 2011-10-11

Patient: 11 year old female weighing 35.0 kg (77.0 pounds)

Reactions: Large Intestine Perforation, Neutropenic Colitis, Stomatitis, Anaemia, Febrile Neutropenia, Pyrexia, Klebsiella Bacteraemia, Death, Thrombocytopenia, Sinusitis, Leukopenia

Adverse event resulted in: death

Suspect drug(s):
Clolar
    Dosage: 60 mg (52 mg/m2), qdx5 (cycle 1)
    Indication: Acute Lymphocytic Leukaemia

Clolar
    Dosage: 60 mg (52 mg/m2), qdx5 (cycle 2)

Other drugs received by patient: Hydrocortisone; Ondansetron; Acetaminophen; Hydroxyzine; Ranitidine



See index of all Clolar side effect reports >>

Drug label data at the top of this Page last updated: 2013-01-18

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