ADVERSE REACTIONS
Most patients treated for hairy cell leukemia in the five NCI-sponsored Phase 2 studies and the Phase 3 SWOG study experienced an adverse event. The following table lists the most frequently occurring adverse events in patients treated with NIPENT (both frontline and IFN-refractory patients) compared with IFN (frontline only), regardless of drug association. The drug association of some adverse events is uncertain as they may be associated with the disease itself (eg, infection, hematologic suppression), but other events, such as the gastrointestinal symptoms, rashes, and abnormal liver function tests, can in many cases be attributed to the drug. Most adverse events that were assessed for severity were either mild or moderate, and diminished in frequency with continued therapy.
|
Percent of Patients
|
All Adverse Eventsa
|
Frontline,
Treated
With NIPENT
N=180
|
Frontline,
Treated
With IFN
N=176
|
IFN-Refractory,
Treated With
NIPENT
N=197
|
Nausea and/or Vomiting
|
63
|
22
|
53b
|
Fever
|
46
|
59
|
42
|
Rash
|
43
|
30
|
26
|
Fatigue
|
42
|
55
|
29
|
Leukopenia
|
22
|
15
|
60
|
Pruritus
|
21
|
6
|
10
|
Coughing/Increased Cough
|
20
|
15
|
17
|
Myalgia
|
19
|
36
|
11
|
Chills
|
19
|
34
|
11
|
Headache
|
17
|
29
|
13
|
Diarrhea
|
17
|
17
|
15
|
Abdominal Pain
|
16
|
15
|
4
|
Anorexia
|
13
|
10
|
16
|
Upper Respiratory Infection
|
13
|
8
|
16
|
Asthenia
|
12
|
13
|
10
|
Stomatitis
|
12
|
7
|
5
|
Rhinitis
|
11
|
15
|
10
|
Dyspnea
|
11
|
13
|
8
|
Anemia
|
8
|
5
|
35
|
Pain
|
8
|
19
|
20
|
Pharyngitis
|
8
|
11
|
10
|
Sweating/Increased Sweating
|
8
|
21
|
10
|
Viral Infection
|
8
|
17
|
NR
|
Infection
|
7c
|
2c
|
36
|
Arthralgia
|
6
|
14
|
3
|
Thrombocytopenia
|
6
|
6
|
32
|
Skin Disorder
|
4
|
5
|
17
|
Allergic Reaction
|
2
|
1
|
11
|
Hepatic Disorder/Elevated Liver Function Testsd
|
2
|
2
|
19
|
Neurologic Disorder, CNS/CNS Toxicity
|
1
|
NR
|
11
|
Lung Disorder/Disease
|
NR
|
1
|
12
|
Nausea
|
NR
|
NR
|
22
|
Genitourinary Disorder
|
NR
|
NR
|
15
|
NR = Not Reported
a Occurring in more than 10% of patients, in any group, regardless of drug association
b Includes only nausea with vomiting
c These figures represent only unspecified infections. Refer to infection table.
d Elevated liver enzymes and liver disorder for SWOG
|
The total incidence for all types of infections is considerably higher for both treatment groups in the SWOG 8691 study than is listed in the table above. An intent-to-treat analysis of infections found that 38% of patients treated with NIPENT and 34% of patients treated with IFN averaged 2.4 and 1.9 documented infections during treatment, respectively. The following table lists the different types of infections that were reported as adverse events during the initial phase of the SWOG study. There were no apparent differences in the types of infection between the 2 treatment groups, with the possible exception of herpes zoster which was reported more frequently for NIPENT (8%) than for IFN (1%).
|
Percent of Patients
|
Type of Infection
|
Frontline, Treated
With NIPENT
N=180
|
Frontline, Treated
With IFN
N=176
|
Upper Respiratory Infection
|
13
|
8
|
Rhinitis
|
11
|
15
|
Herpes Zoster
|
8
|
1
|
Pharyngitis
|
8
|
11
|
Viral Infection
|
8
|
17
|
Infection (Unspecified)
|
7
|
2
|
Sinusitis
|
6
|
4
|
Cellulitis
|
6
|
3
|
Bacterial Infection
|
5
|
4
|
Pneumonia
|
5
|
7
|
Conjunctivitis
|
4
|
2
|
Furunculosis
|
4
|
<1
|
Herpes Simplex
|
4
|
1
|
Bronchitis
|
3
|
2
|
Sepsis
|
3
|
2
|
Urinary Tract Infection
|
3
|
3
|
Abscess, Skin
|
2
|
4
|
Moniliasis, Oral
|
2
|
<1
|
Mycotic Infection, Skin
|
<1
|
3
|
Osteomyelitis
|
1
|
0
|
The drug relatedness of the adverse events listed below cannot be excluded. The following adverse events occurred in 3% to 10% of NIPENT-treated patients in the initial phase of the SWOG study:
Body as a Whole
—Chest Pain, Death, Face Edema, Peripheral Edema
Cardiovascular System
—Hemorrhage, Hypotension
Digestive System
—Dental Abnormalities, Dyspepsia, Flatulence, Gingivitis
Hemic and Lymphatic System
—Agranulocytosis
Laboratory Deviations
—Elevated Creatinine
Musculoskeletal System
—Arthralgia
Nervous System
—Confusion, Dizziness, Insomnia, Paresthesia, Somnolence
Psychobiologic Function
—Anxiety, Depression, Nervousness
Respiratory System
—Asthma
Skin & Appendages
—Skin Dry, Urticaria
The remaining adverse events which occurred in less than 3% of NIPENT-treated patients during the initial phase of the SWOG study:
Body as a Whole
—Flu-like Symptoms, Hangover Effect, Neoplasm
Cardiovascular System
—Angina Pectoris, Arrhythmia, A-V Block, Bradycardia, Extrasystoles Ventricular, Heart Arrest, Heart Failure, Hypertension, Pericardial Effusion, Phlebitis, Pulmonary Embolus, Sinus Arrest, Tachycardia, Thrombophlebitis Deep, Vasculitis
Digestive System
—Constipation, Dysphagia, Glossitis, Ileus
Hemic and Lymphatic System
—Acute Leukemia, Anemia-Hemolytic, Aplastic Anemia
Laboratory Deviations
—Hypercalcemia, Hyponatremia
Musculoskeletal System
—Arthritis, Gout
Nervous System
—Amnesia, Ataxia, Convulsions, Dreaming Abnormal, Dysarthria, Encephalitis, Hyperkinesia, Meningism, Neuralgia, Neuritis, Neuropathy, Paralysis, Syncope, Twitching, Vertigo
Psychobiologic Function
—Decrease/Loss Libido, Emotional Lability, Hallucination, Hostility, Neurosis, Thinking Abnormal
Respiratory System
—Bronchospasm, Larynx Edema
Skin and Appendages
—Acne, Alopecia, Eczema, Petechial Rash, Photosensitivity Reaction
Special Senses
—Amblyopia, Deafness, Earache, Eyes Dry, Labyrinthitis, Lacrimation Disorder, Nonreactive Eye, Photophobia, Retinopathy, Tinnitus, Unusual Taste, Vision Abnormal, Watery Eyes
Urogenital System
—Amenorrhea, Breast Lump, Impotence, Kidney Function Abnormal, Nephropathy, Renal Failure, Renal Insufficiency, Renal Stone
One patient with hairy cell leukemia treated with NIPENT during another clinical study developed unilateral uveitis with vision loss.
Nineteen (5%) patients withdrew from the Phase 3 SWOG 8691 study because of adverse events; 9 during initial NIPENT treatment, 4 during NIPENT crossover, 5 during initial IFN treatment, and 1 during both initial IFN treatment and NIPENT crossover. In the Phase 2 studies in IFN-refractory hairy cell leukemia, 11% of patients withdrew from treatment with NIPENT due to an adverse event.
|
REPORTS OF SUSPECTED NIPENT SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Nipent. The information is not vetted and should not be considered as verified clinical evidence.
Possible Nipent side effects / adverse reactions in 47 year old male
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-18
Patient: 47 year old male weighing 130.9 kg (288.0 pounds)
Reactions: Lymphopenia
Suspect drug(s):
Cyclophosphamide
Dosage: 600 mg/m2 (1506 mg total dose), day 1 of weeks 1,5,9.,14,17,21
Indication: Chronic Lymphocytic Leukaemia
Start date: 2011-08-04
End date: 2011-08-04
Nipent
Dosage: 4 mg/m2 (10 mg total dose) on weeks 1,5,9,13,17,21
Indication: Chronic Lymphocytic Leukaemia
Start date: 2011-08-04
End date: 2011-08-04
Rituxan
Dosage: 375 mg.m2 (941 mg total dose), on weeks 1,5,9,13,17,21; week 1,3 days/week; weeks 5-21; 1 day/week
Indication: Chronic Lymphocytic Leukaemia
Start date: 2011-08-04
End date: 2011-08-04
Possible Nipent side effects / adverse reactions in 70 year old male
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-27
Patient: 70 year old male weighing 67.9 kg (149.4 pounds)
Reactions: Dyspnoea, Anaemia, Muscular Weakness, Hypoaesthesia, Fall, Paraesthesia, Fatigue, Dehydration, Platelet Count Decreased, Cytomegalovirus Infection, Blood Pressure Decreased, Immobile, Infestation
Adverse event resulted in: hospitalization
Suspect drug(s):
(Rituximab)
Dosage: 758 mg, not reported
Indication: Chronic Lymphocytic Leukaemia
Start date: 2010-12-27
End date: 2011-05-18
Campath
Dosage: 30 mg, tiw x 18 weeks, subcutaneous
Indication: Chronic Lymphocytic Leukaemia
Start date: 2011-07-29
End date: 2011-09-14
Cyclophosphamide
Dosage: 1212 mg
Indication: Chronic Lymphocytic Leukaemia
Start date: 2010-12-27
End date: 2011-05-18
Nipent
Dosage: 8 mg
Indication: Chronic Lymphocytic Leukaemia
Start date: 2010-12-27
End date: 2011-05-18
Possible Nipent side effects / adverse reactions in 43 year old male
Reported by a health professional (non-physician/pharmacist) from United States on 2011-11-29
Patient: 43 year old male
Reactions: Vomiting, Diarrhoea, Nausea, Epstein-Barr Virus Associated Lymphoproliferative Disorder
Adverse event resulted in: hospitalization
Suspect drug(s):
Busulfan
Dosage: not reported, not reported, unknown, (unknown)
Indication: Stem Cell Transplant
Nipent
Dosage: not reported, not reported, unknown, (unknown)
Indication: Stem Cell Transplant
Other drugs received by patient: Rituxan
|