A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Campath Side Effects, and Drug Interactions - Alemtuzumab
Campath Side Effects, and Drug Interactions - Alemtuzumab
SIDE EFFECTS
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 adverse reaction information
from clinical trials does, however, provide a basis for identifying the adverse
events that appear to be related to drug use and for approximating rates.
Safety data, except where indicated, are based on 149 patients
with B-CLL enrolled in studies of Campath as a single agent administered at
a maintenance dose of 30 mg intravenously three times weekly for 4 to 12 weeks.
able 2 lists adverse events including severe or life threatening (NCI-CTC Grade
3 or 4) adverse events reported in > 5% of the patients. More detailed information
and follow-up were available for Study 1 (93 patients),therefore the narrative
description of certain events, noted below, is based on this study.
Infusion-Related Adverse Events
Infusion-related adverse events resulted in discontinuation
of Campath therapy in 6% of the patients enrolled in Study 1.The most commonly
reported infusion-related adverse events on this study included rigors in 89%
of patients, drug-related fever in 83%, nausea in 47%, vomiting in 33%, and
hypotension in 15%. Other frequently reported infusion-related events include,
rash in 30% of patients, fatigue in 22%, urticaria in 22%, dyspnea in 17%, pruritus
in 14%, headache in 13%,and diarrhea in 13%.Similar types of adverse events
were reported on the supporting studies (see Table 2). Acute infusion-related
events were most common during the first week of therapy. Antihistamines, acetaminophen,
antiemetics, meperidine, and corticosteroids as well as incremental dose escalation
were used to prevent or ameliorate infusion-related events. (See WARNINGS
and DOSAGE AND ADMINISTRATION.)
Infections
On Study 1, all patients were required to receive anti-herpes
and anti-PCP prophylaxis (see DOSAGE AND ADMINISTRATION)
and were followed for infections for 6 months. Forty (43%) of 93 patients experienced
59 infections (one or more infections per patient) related to Campath during
treatment or within 6 months of the last dose. Of these,34 (37%) patients experienced
42 infections that were of Grade 3 or 4 severity; 11 (18%) were fatal. Fifty-five
percent of the Grade 3 or 4 infections occurred during treatment or within 30
days of last dose. In addition one or more episodes of febrile neutropenia (ANC
£?500/mL) were
reported in 10% of patients.
The following types of infections were reported in Study 1:Grade
3 or 4 sepsis in 12% of patients with one fatality, Grade 3 or 4 pneumonia in
15% with five fatalities, and opportunistic infections in 17% with four fatalities.
Candida infections were reported in 5% of patients; CMV infections in 8% (4%
of Grade 3 or 4 severity); Aspergillosis in 2% with fatal Aspergillosis in 1%;
fatal Mucormycosis in 2%; fatal Cryptococcal pneumonia in 1%; Listeria monocytogenes
meningitis in 1%; disseminated Herpes zoster in 1%; Grade 3 Herpes
simplex in 2%; and Torulopsis pneumonia in 1%. PCP pneumonia occurred in
one (1%) patient who discontinued PCP prophylaxis.
On Studies 2 and 3 in which anti-herpes and anti-PCP prophylaxis
was optional,37 (66%) patients had 47 infections while or after receiving Campath
therapy. In addition to the opportunistic infections reported above, the following
types of related events were observed on these studies: interstitial pneumonitis
of unknown etiology and progressive multifocal leukoencephalopathy.
Hematologic Adverse Events
Pancytopenia/Marrow Hypoplasia: Campath therapy was
permanently discontinued in six (6%) patients due to pancytopenia/marrow hypoplasia.
Two (2%) cases of pancytopenia/ marrow hypoplasia were fatal.
Anemia: Forty-four (47%) patients had one or more episodes
of new onset NCI-CTC Grade 3 or 4 anemia. Sixty-two (67%) patients required
RBC transfusions. In addition, erythropoietin use was reported in nineteen (20%)
patients. Autoimmune hemolytic anemia secondary to Campath therapy was reported
in 1% of patients. Positive Coombs test without hemolysis was reported in 2%.(See
BOXED WARNING.)
Neutropenia: Sixty-five (70%) patients had one or more
episodes of NCI-CTC Grade 3 or 4 neutropenia. Median duration of Grade 3 or
4 neutropenia was 28 days (range:2 – 165 days).(See Infections.)
Thrombocytopenia:
Forty-eight (52%) patients had one or more episodes of new onset Grade 3 or
4 thrombocytopenia. Median duration of thrombocytopenia was 21 days (range:
2 – 165 days). Thirty-five (38%) patients required platelet transfusions for
management of thrombocytopenia. Autoimmune thrombocytopenia was reported in
2% of patients with one fatal case of Campath-related autoimmune thrombocytopenia.(See
BOXED WARNING.)
Lymphopenia: The median CD4+ count at 4 weeks
after initiation of Campath therapy was 2 (two)/mL,
at 2 months after discontinuation of Campath therapy,207/mL,and
6 months after discontinuation,470/mL.The pattern
of change in median CD8+ lymphocyte counts was similar to that of
CD4+ cells. In some patients treated with Campath,CD4+ and
CD8+ lymphocyte counts had not returned to baseline levels at longer
than 1 year post therapy.
|
Table 2: Adverse Events in > 5% of the B-CLL Study
Population During Treatment or Within 30 Days (N = 149)
|
|
|
B-CLL STUDIES (N = 149)
|
|
Adverse Event:
|
ANY Grade (%)
|
Grade 3 or 4 (%)
|
|
Body As A Whole
|
|
|
|
Rigors
|
86
|
16
|
|
Fever
|
85
|
19
|
|
Fatigue
|
34
|
5
|
|
Pain, Skeletal Pain
|
24
|
2
|
|
Anorexia
|
20
|
3
|
|
Asthenia
|
13
|
4
|
|
Edema, Peripheral Edema
|
13
|
1
|
|
Back Pain
|
10
|
3
|
|
Chest Pain
|
10
|
1
|
|
Malaise
|
9
|
1
|
|
Temperature Change Sensation
|
5
|
–
|
|
Cardiovascular Disorders, General
|
|
|
|
Hypotension
|
32
|
5
|
|
Hypertension
|
11
|
2
|
|
Heart Rate & Rhythm Disorders
|
|
|
|
Tachycardia, SVT
|
11
|
3
|
|
Central & Peripheral Nervous System Disorders
|
|
|
|
Headache
|
24
|
1
|
|
Dysthesias
|
15
|
–
|
|
Dizziness
|
12
|
1
|
|
Tremor
|
7
|
–
|
|
Gastrointestinal Disorders
|
|
|
|
Nausea
|
54
|
2
|
|
Vomiting
|
41
|
4
|
|
Diarrhea
|
22
|
1
|
|
Stomatitis, Ulcerative Stomatitis, Mucositis
|
14
|
1
|
|
Abdominal Pain
|
11
|
2
|
|
Dyspepsia
|
10
|
–
|
|
Constipation
|
9
|
1
|
|
Hematologic Disorders
|
|
|
|
WBC Disorders: Neutropenia
|
85
|
64
|
|
RBC Disorders: Anemia
|
80
|
38
|
|
Pancytopenia
|
5
|
3
|
|
Platelet, Bleeding & Clotting Disorders
|
|
|
|
Thrombocytopenia
|
72
|
50
|
|
Purpura
|
8
|
–
|
|
Epistaxis
|
7
|
1
|
|
Musculoskeletal Disorders
|
|
|
|
Myalgias
|
11
|
–
|
|
Psychiatric Disorders
|
|
|
|
Insomnia
|
10
|
–
|
|
Depression
|
7
|
1
|
|
Somnolence
|
5
|
1
|
|
Resistance Mechanism Disorders
|
|
|
|
Sepsis
|
15
|
10
|
|
Herpes Simplex
|
11
|
1
|
|
Moniliasis
|
8
|
1
|
|
Infection (other viral or unidentified)
|
7
|
1
|
|
Respiratory System Disorders
|
|
|
|
Dyspnea
|
26
|
9
|
|
Cough
|
25
|
2
|
|
Bronchitis, Pneumonitis
|
21
|
13
|
|
Pneumonia
|
16
|
10
|
|
Pharyngitis
|
12
|
–
|
|
Bronchospasm
|
9
|
2
|
|
Rhinitis
|
7
|
–
|
|
Skin & Appendage Disorders
|
|
|
|
Rash, Maculopapular Rash, Erythematous Rash
|
40
|
3
|
|
Urticaria
|
30
|
5
|
|
Pruritus
|
24
|
1
|
|
Sweating increased
|
19
|
1
|
Serious adverse events
The following serious adverse events, defined as events which
result in death, requiring or prolonging hospitalization, requiring medical
intervention to prevent hospitalization, or malignancy, were reported in at
least one patient treated on studies where Campath was used as a single agent
(and are not reported in Table 2).These studies were conducted in patients with
lymphocytic leukemia and lymphoma (N = 745) and in patients with non-malignant
diseases (N =152) such as rheumatoid arthritis, solid organ transplant, or multiple
sclerosis.
Body As A Whole: allergic reactions, anaphylactoid reaction,
ascites, hypovolemia, influenza-like syndrome, mouth edema, neutropenic fever,
syncope Cardiovascular
Cardiovascular Disorders: cardiac failure, cyanosis, atrial fibrillation, cardiac arrest, ventricular arrhythmia,
ventricular tachycardia, angina pectoris, coronary artery disorder, myocardial infarction, pericarditis
Central and Peripheral Nervous System Disorders: abnormal
gait,aphasia, coma, grand mal convulsions, paralysis, meningitis
Endocrine Disorders: hyperthyroidism
Gastrointestinal System Disorders: duodenal ulcer, esophagitis,
gingivitis, gastroenteritis, GI hemorrhage, hematemesis, hemorrhoids, intestinal
obstruction,intestinal perforation, melena, paralytic ileus, peptic ulcer, pseudomembranous
colitis, colitis, pancreatitis, peritonitis, hyperbilirubinemia, hepatic failure,
hepatocellular damage, hypoalbuminemia, biliary pain
Hearing and Vestibular Disorders: decreased hearing
Metabolic and Nutritional Disorders: acidosis, aggravated
diabetes mellitus, dehydration, fluid overload, hyperglycemia, hyperkalemia,
hypokalemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, respiratory
alkalosis
Musculoskeletal System Disorders: arthritis or worsening
arthritis, arthropathy, bone fracture, myositis, muscle atrophy, muscle weakness,
osteomyelitis, polymyositis
Neoplasms: malignant lymphoma, malignant testicular
neoplasm, prostatic cancer, plasma cell dyscrasia, secondary leukemia, squamous
cell carcinoma, transformation to aggressive lymphoma, transformation to prolymphocytic
leukemia
Platelet, Bleeding, and Clotting Disorders: coagulation
disorder, disseminated intravascular coagulation, hematoma, pulmonary embolism,
thrombocythemia
Psychiatric Disorders: confusion, hallucinations, nervousness,
abnormal thinking, apathy
White Cell and RES Disorders: agranulocytosis, aplasia,
decreased haptoglobin, lymphadenopathy, marrow depression
Red Blood Cell Disorders: hemolysis, hemolytic anemia, splenic infarction, splenomegaly
Reproductive System Disorders: cervical dysplasia
Resistance Mechanism Disorders: abscess, bacterial infection,
Herpes zoster infection, Pneumocystis carinii infection, otitis
media, Tuberculosis infection, viral infection
Respiratory System Disorders: asthma, bronchitis, chronic
obstructive pulmonary disease, hemoptysis, hypoxia, pleural effusion, pleurisy,
pneumothorax, pulmonary edema, pulmonary fibrosis, pulmonary infiltration, respiratory
depression, respiratory insufficiency, sinusitis, stridor, throat tightness
Skin and Appendages Disorders: angioedema, bullous eruption,
cellulitis, purpuric rash
Special Senses Disorders: taste loss
Urinary System Disorders : abnormal renal function,
acute renal failure, anuria, facial edema, hematuria, toxic nephropathy, ureteric
obstruction, urinary retention, urinary tract infection
Vascular (Extracardiac) Disorders: cerebral hemorrhage,
cerebrovascular disorder, deep vein thrombosis, increased capillary fragility,
intracranial hemorrhage, phlebitis, subarachnoid hemorrhage, thrombophlebitis
Vision Disorders : endophthalmitis
DRUG INTERACTIONS
Drug/Laboratory Interactions
No formal drug interaction studies have been performed with
Campath. An immune response to Campath may interfere with subsequent diagnostic
serum tests that utilize antibodies.
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