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Campath (Alemtuzumab) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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

  • Cytopenias [see WARNINGS AND PRECAUTIONS]
  • Infusion Reactions   [see WARNINGS AND PRECAUTIONS]
  • Immunosuppression/Infections [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions with Campath are: infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (CMV viremia, CMV infection, other infections), gastrointestinal symptoms (nausea, emesis, abdominal pain), and neurological symptoms (insomnia, anxiety). The most common serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

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 below reflect exposure to Campath in 296 patients with CLL of whom 147 were previously untreated and 149 received at least 2 prior chemotherapy regimens. The median duration of exposure was 11.7 weeks for previously untreated patients and 8 weeks for previously treated patients.

Lymphopenia: Severe lymphopenia and a rapid and sustained decrease in lymphocyte subsets occurred in previously untreated and previously treated patients following administration of Campath. In previously untreated patients, the median CD4+ was 0 cells/μL at one month after treatment and 238 cells/μL [25-75% interquartile range 115 to 418 cells/μL at 6 months post-treatment   [see WARNINGS AND PRECAUTIONS] .

Neutropenia: In previously untreated patients, the incidence of Grade 3 or 4 neutropenia was 42% with a median time to onset of 31 days and a median duration of 37 days. In previously treated patients, the incidence of Grade 3 or 4 neutropenia was 64% with a median duration of 28 days. Ten percent of previously untreated patients and 17% of previously treated patients received granulocyte colony stimulating factors.

Anemia: In previously untreated patients, the incidence of Grade 3 or 4 anemia was 12% with a median time to onset of 31 days and a median duration of 8 days. In previously treated patients, the incidence of Grade 3 or 4 anemia was 38%. Seventeen percent of previously untreated patients and 66% of previously treated patients received either erythropoiesis stimulating agents, transfusions or both.

Thrombocytopenia: In previously untreated patients, the incidence of Grade 3 or 4 thrombocytopenia was 14% with a median time to onset of 9 days and a median duration of 14 days. In previously treated patients, the incidence of Grade 3 or 4 thrombocytopenia was 52% with a median duration of 21 days. Autoimmune thrombocytopenia was reported in 2% of previously treated patients with one fatality.

Infusion reactions: Infusion reactions, which included pyrexia, chills, hypotension, urticaria, and dyspnea, were common. Grade 3 and 4 pyrexia and/or chills occurred in approximately 10% of previously untreated patients and in approximately 35% of previously treated patients. The occurrence of infusion reactions was greatest during the initial week of treatment and decreased with subsequent doses of Campath. All patients were pretreated with antipyretics and antihistamines; additionally, 43% of previously untreated patients received glucocorticoid pre-treatment.

Infections: In the study of previously untreated patients, patients were tested weekly for CMV using a PCR assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. CMV infection occurred in 16% (23/147) of previously untreated patients; approximately one-third of these infections were serious or life threatening. In studies of previously treated patients in which routine CMV surveillance was not required, CMV infection was documented in 6% (9/149) of patients; nearly all of these infections were serious or life threatening.

Other infections were reported in approximately 50% of patients across all studies. Grade 3 - 5 sepsis ranged from 3% to 10% across studies and was higher in previously treated patients. Grade 3 - 4 febrile neutropenia ranged from 5 to 10% across studies and was higher in previously treated patients. Infection-related fatalities occurred in 2% of previously untreated patients and 16% of previously treated patients. There were 198 episodes of other infection in 109 previously untreated patients; 16% were bacterial, 7% were fungal, 4% were other viral, and in 73%, the organism was not identified.

Cardiac: Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion; dysrhythmias were Grade 3 or 4 in 1% of patients.

Previously Untreated Patients

Table 1  contains selected adverse reactions observed in 294 patients randomized (1:1) to receive Campath or chlorambucil as first line therapy for B-CLL. Campath was administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks. The median duration of therapy was 11.7 weeks with a median weekly dose of 82 mg (25-75% interquartile range: 69 mg – 90 mg).

Table 1
Per Patient Incidence of Selected1 Adverse Reactions in Treatment Naive B-CLL Patients
Campath (n=147)Chlorambucil (n=147)
    
All Grades2
%

Grades 3-4
%

All Grades
%

Grades
3-4
%

Blood and Lymphatic System DisordersLymphopenia979791
Neutropenia77425126
Anemia76135418
Thrombocytopenia71137014
General Disorders and Administration Site ConditionsPyrexia6910111
Chills53310
Infections and InfestationsCMV viremia355480
CMV infection16500
Other infections74216510
Skin and Subcutaneous Tissue DisordersUrticaria16210
Rash13140
Erythema4010
Vascular DisordersHypotension16100
Hypertension14521
Nervous System DisordersHeadache14180
Tremor3010
Respiratory, Thoracic and Mediastinal DisordersDyspnea14473
Gastrointestinal DisordersDiarrhea10140
Psychiatric DisordersInsomnia10030
Anxiety8010
Cardiac DisordersTachycardia10010

1Adverse reactions occurring at a higher relative frequency in the Campath arm
2NCI CTC version 2.0 for adverse reactions; NCI CTCAE version 3.0 for laboratory values
3CMV viremia (without evidence of symptoms) includes both cases of single PCR positive test results and of confirmed CMV viremia (≥ 2 occasions in consecutive samples 1 week apart). For the latter, ganciclovir (or equivalent) was initiated per protocol.

Previously Treated Patients

Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in  Table 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. Using an ELISA assay, anti-human antibodies (HAHA) were detected in 11 of 133 (8.3%) previously untreated patients. In addition, two patients were weakly positive for neutralizing activity. Limited data suggest that the anti-Campath antibodies did not adversely affect tumor response. Four of 211 (1.9%) previously-treated patients were found to have antibodies to Campath following treatment.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Campath with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

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

Fatal infusion reactions: [see WARNINGS AND PRECAUTIONS] .

Cardiovascular: congestive heart failure,   cardiomyopathy, decreased ejection fraction (in patients previously treated with cardiotoxic agents).

Gastrointestinal: GI hemorrhage

Hepatic: elevation of hepatic enzymes

Immune disorders: Goodpasture’s syndrome, Graves’ disease, aplastic anemia, Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness, Coombs test positive, transfusion associated Graft versus Host Disease.

Infections: Epstein-Barr Virus (EBV) , progressive multifocal leukoencephalopathy (PML), hepatitis B virus.

Metabolic: tumor lysis syndrome, dehydration

Neoplasms: EBV-associated lymphoproliferative disorder

Neurologic: dizziness, optic neuropathy

Psychiatric: confusion

Renal: abnormal renal function



REPORTS OF SUSPECTED CAMPATH SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Campath side effects / adverse reactions in 68 year old female

Reported by a physician from Germany on 2011-10-06

Patient: 68 year old female weighing 90.1 kg (198.2 pounds)

Reactions: Oesophagitis

Suspect drug(s):
Campath
    Dosage: 30 mg, qd
    End date: 2011-09-05

Campath
    Dosage: 30 mg qd, cycle 1
    Indication: T-Cell Prolymphocytic Leukaemia
    Start date: 2011-06-16



Possible Campath side effects / adverse reactions in 55 year old male

Reported by a physician from United Kingdom on 2011-10-11

Patient: 55 year old male

Reactions: Posterior Reversible Encephalopathy Syndrome

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Campath
    Dosage: 30 mg, 3x/w
    Indication: T-Cell Prolymphocytic Leukaemia

Pentostatin
    Dosage: 7.2 mg (4 mg/m2), unk
    Indication: T-Cell Prolymphocytic Leukaemia



Possible Campath side effects / adverse reactions in 68 year old female

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

Patient: 68 year old female

Reactions: Bronchopulmonary Aspergillosis, Scedosporium Infection, Chronic Lymphocytic Leukaemia

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Cyclophosphamide
    Dosage: unk
    Indication: Chronic Lymphocytic Leukaemia
    Start date: 2007-11-01

Fludara
    Dosage: unk
    Indication: Chronic Lymphocytic Leukaemia
    Start date: 2007-11-01

Campath
    Dosage: unk
    Indication: Chronic Lymphocytic Leukaemia
    Start date: 2007-11-01

Other drugs received by patient: Prednisone; Insulin



See index of all Campath side effect reports >>

Drug label data at the top of this Page last updated: 2008-10-31

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