ADVERSE REACTIONS
The most common drug-related adverse reactions can be classified into 4 symptom complexes: gastrointestinal symptoms (diarrhea, nausea, anorexia, weight decrease, vomiting, constipation), constitutional symptoms (fatigue, chills), hematologic abnormalities (thrombocytopenia, anemia), and taste disorders (dysgeusia, dry mouth). The most common serious drug-related adverse reactions were pulmonary embolism and anemia.
Clinical Trials Experience
The safety of ZOLINZA was evaluated in 107 CTCL patients in two single arm clinical studies in which 86 patients received 400 mg once daily.
The data described below reflect exposure to ZOLINZA 400 mg once daily in the 86 patients for a median number of 97.5 days on therapy (range 2 to 480+ days). Seventeen (19.8%) patients were exposed beyond 24 weeks and 8 (9.3%) patients were exposed beyond 1 year. The population of CTCL patients studied was 37 to 83 years of age, 47.7% female, 52.3% male, and 81.4% white, 16.3% black, and 1.2% Asian or multi-racial.
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.
Common Adverse Reactions
Table 1 summarizes the frequency of CTCL patients with specific adverse events, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 3.0).
Table 1 Clinical or Laboratory Adverse Events Occurring in CTCL Patients (Incidence ≥10% of patients) | ZOLINZA 400 mg once daily (N=86) |
| Adverse Events | All Grades | Grades 3-5
|
| n | % | n | % |
| Fatigue | 45 | 52.3 | 3 | 3.5 |
| Diarrhea | 45 | 52.3 | 0 | 0.0 |
| Nausea | 35 | 40.7 | 3 | 3.5 |
| Dysgeusia | 24 | 27.9 | 0 | 0.0 |
| Thrombocytopenia | 22 | 25.6 | 5 | 5.8 |
| Anorexia | 21 | 24.4 | 2 | 2.3 |
| Weight Decreased | 18 | 20.9 | 1 | 1.2 |
| Muscle Spasms | 17 | 19.8 | 2 | 2.3 |
| Alopecia | 16 | 18.6 | 0 | 0.0 |
| Dry Mouth | 14 | 16.3 | 0 | 0.0 |
| Blood Creatinine Increased | 14 | 16.3 | 0 | 0.0 |
| Chills | 14 | 16.3 | 1 | 1.2 |
| Vomiting | 13 | 15.1 | 1 | 1.2 |
| Constipation | 13 | 15.1 | 0 | 0.0 |
| Dizziness | 13 | 15.1 | 1 | 1.2 |
| Anemia | 12 | 14.0 | 2 | 2.3 |
| Decreased Appetite | 12 | 14.0 | 1 | 1.2 |
| Peripheral Edema | 11 | 12.8 | 0 | 0.0 |
| Headache | 10 | 11.6 | 0 | 0.0 |
| Pruritus | 10 | 11.6 | 1 | 1.2 |
| Cough | 9 | 10.5 | 0 | 0.0 |
| Upper Respiratory Infection | 9 | 10.5 | 0 | 0.0 |
| Pyrexia | 9 | 10.5 | 1 | 1.2 |
The frequencies of more severe thrombocytopenia, anemia [see Warnings and Precautions] and fatigue were increased at doses higher than 400 mg once daily of ZOLINZA.
Serious Adverse Reactions
The most common serious adverse events, regardless of causality, in the 86 CTCL patients in two clinical studies were pulmonary embolism reported in 4.7% (4/86) of patients, squamous cell carcinoma reported in 3.5% (3/86) of patients and anemia reported in 2.3% (2/86) of patients. There were single events of cholecystitis, death (of unknown cause), deep vein thrombosis, enterococcal infection, exfoliative dermatitis, gastrointestinal hemorrhage, infection, lobar pneumonia, myocardial infarction, ischemic stroke, pelvi-ureteric obstruction, sepsis, spinal cord injury, streptococcal bacteremia, syncope, T-cell lymphoma, thrombocytopenia and ureteric obstruction.
Discontinuations
Of the CTCL patients who received the 400-mg once daily dose, 9.3% (8/86) of patients discontinued ZOLINZA due to adverse events. These adverse events, regardless of causality, included anemia, angioneurotic edema, asthenia, chest pain, exfoliative dermatitis, death, deep vein thrombosis, ischemic stroke, lethargy, pulmonary embolism, and spinal cord injury.
Dose Modifications
Of the CTCL patients who received the 400-mg once daily dose, 10.5% (9/86) of patients required a dose modification of ZOLINZA due to adverse events. These adverse events included increased serum creatinine, decreased appetite, hypokalemia, leukopenia, nausea, neutropenia, thrombocytopenia and vomiting. The median time to the first adverse event resulting in dose reduction was 42 days (range 17 to 263 days).
Laboratory Abnormalities
Laboratory abnormalities were reported in all of the 86 CTCL patients who received the 400-mg once-daily dose.
Increased serum glucose was reported as a laboratory abnormality in 69% (59/86) of CTCL patients who received the 400-mg once daily dose; only 4 of these abnormalities were severe (Grade 3). Increased serum glucose was reported as an adverse event in 8.1% (7/86) of CTCL patients who received the 400-mg once daily dose. [See Warnings and Precautions.]
Transient increases in serum creatinine were detected in 46.5% (40/86) of CTCL patients who received the 400-mg once daily dose. Of these laboratory abnormalities, 34 were NCI CTCAE Grade 1, 5 were Grade 2, and 1 was Grade 3.
Proteinuria was detected as a laboratory abnormality (51.4%) in 38 of 74 patients tested. The clinical significance of this finding is unknown.
Dehydration
Based on reports of dehydration as a serious drug-related adverse event in clinical trials, patients were instructed to drink at least 2 L/day of fluids for adequate hydration. [See Warnings and Precautions (5.3, 5.6).]
Adverse Reactions in Non-CTCL Patients
The frequencies of individual adverse events were substantially higher in the non-CTCL population. Drug-related serious adverse events reported in the non-CTCL population which were not observed in the CTCL population included single events of blurred vision, asthenia, hyponatremia, tumor hemorrhage, Guillain-Barré syndrome, renal failure, urinary retention, cough, hemoptysis, hypertension, and vasculitis.
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REPORTS OF SUSPECTED ZOLINZA SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Zolinza. The information is not vetted and should not be considered as verified clinical evidence.
Possible Zolinza side effects / adverse reactions in 48 year old male
Reported by a individual with unspecified qualification from Korea, Republic of on 2011-10-07
Patient: 48 year old male
Reactions: Haemoglobin Decreased, Fatigue, Enteritis, Decreased Appetite
Adverse event resulted in: hospitalization
Suspect drug(s):
Xeloda
Dosage: 1600 mg/bid po ; 15600 mg/bid po ; 1200 mg/bid po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-09-17
Xeloda
Dosage: 1600 mg/bid po ; 15600 mg/bid po ; 1200 mg/bid po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-07-29
End date: 2011-08-11
Xeloda
Dosage: 1600 mg/bid po ; 15600 mg/bid po ; 1200 mg/bid po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-08-20
End date: 2011-09-02
Cisplatin
Dosage: 98.4 mg/daily iv ; 98.4 mg/daily iv ; 94.8 mg/daily iv
Indication: Gastric Cancer
Start date: 2011-08-20
End date: 2011-08-20
Cisplatin
Dosage: 98.4 mg/daily iv ; 98.4 mg/daily iv ; 94.8 mg/daily iv
Indication: Gastric Cancer
Start date: 2011-09-17
Cisplatin
Dosage: 98.4 mg/daily iv ; 98.4 mg/daily iv ; 94.8 mg/daily iv
Indication: Gastric Cancer
Start date: 2011-07-29
End date: 2011-07-29
Zolinza
Dosage: 400 mg/daily po ;400 mg/daily po ; 300 mg/daily po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-09-17
Zolinza
Dosage: 400 mg/daily po ;400 mg/daily po ; 300 mg/daily po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-08-20
End date: 2011-09-02
Zolinza
Dosage: 400 mg/daily po ;400 mg/daily po ; 300 mg/daily po
Administration route: Oral
Indication: Gastric Cancer
Start date: 2011-07-29
End date: 2011-08-11
Other drugs received by patient: Ulcermin; Sodium Bicarbonate
Possible Zolinza side effects / adverse reactions in 60 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-28
Patient: 60 year old female weighing 75.7 kg (166.5 pounds)
Reactions: Sepsis, Pyrexia
Adverse event resulted in: death, hospitalization
Suspect drug(s):
Azacitidine
Dosage: 75 mg/m2, sc or iv on days 1-7
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-03
Gemtuzumab Ozogamicin
Dosage: 3 mg/m2, over 2 hrs on days 4 and 8
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-07
End date: 2011-09-07
Zolinza
Dosage: 400 mg, 1x/day on days 1-9
Administration route: Oral
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-03
Possible Zolinza side effects / adverse reactions in 60 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2011-11-07
Patient: 60 year old female weighing 75.7 kg (166.5 pounds)
Reactions: Sepsis, Pyrexia
Adverse event resulted in: death, hospitalization
Suspect drug(s):
Zolinza
Dosage: 400 mg, 1x/day on days 1-9
Administration route: Oral
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-03
Gemtuzumab Ozogamicin
Dosage: 3 mg/m2, over 2 hrs on days 4 and 8
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-07
End date: 2011-09-07
Azacitidine
Dosage: 75 mg/m2, sc or iv on days 1-7
Indication: Acute Myeloid Leukaemia
Start date: 2011-09-03
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