MabCampath

1 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

2 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
MabCampath 10 mg/ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One ml contains 10 mg of alemtuzumab. 
Each ampoule contains 30 mg of alemtuzumab. 
 
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 
21-28 kD lymphocyte cell surface glycoprotein (CD52). The antibody is produced in mammalian cell 
(Chinese Hamster Ovary) suspension culture in a nutrient medium. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
Colourless to slightly yellow concentrate. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
MabCampath is indicated for the treatment of patients with B-cell chronic lymphocytic leukaemia (B-
CLL) for whom fludarabine combination chemotherapy is not appropriate. 
 
4.2 Posology and method of administration 
 
MabCampath should be administered under the supervision of a physician experienced in the use of 
cancer therapy. 
 
Posology 
 
During the first week of treatment, MabCampath should be administered in escalating doses: 3 mg on 
day 1, 10 mg on day 2 and 30 mg on day 3 assuming that each dose is well tolerated. Thereafter, the 
recommended dose is 30 mg daily administered 3 times weekly on alternate days up to a maximum of 
12 weeks.  
 
In most patients, dose escalation to 30 mg can be accomplished in 3-7 days. However, if acute 
moderate to severe adverse reactions such as hypotension, rigors, fever, shortness of breath, chills, 
rashes and bronchospasm (some of which may be due to cytokine release) occur at either the 3 mg or 
10 mg dose levels, then those doses should be repeated daily until they are well tolerated before 
further dose escalation is attempted (see section 4.4). 
 
Median duration of treatment was 11.7 weeks for first-line patients and 9.0 weeks for previously 
treated patients.  
 
Once a patient meets all laboratory and clinical criteria for a complete response, MabCampath should 
be discontinued and the patient monitored. If a patient improves (i.e. achieves a partial response or 
stable disease) and then reaches a plateau without further improvement for 4 weeks or more, then 
MabCampath should be discontinued and the patient monitored. Therapy should be discontinued if 
there is evidence of disease progression. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

3 
 

 
Concomitant medicinal products 
 
Premedications 
 
Patients should be premedicated with oral or intravenous steroids, an appropriate antihistamine and 
analgesic 30-60 minutes prior to each MabCampath infusion during dose escalation and as clinically 
indicated thereafter (see section 4.4). 
 
Prophylactic antibiotics 
 
Antibiotics and antivirals should be administered routinely to all patients throughout and following 
treatment (see section 4.4).  
 
Dose modification guidelines 
 
There are no dose modifications recommended for severe lymphopenia given the mechanism of action 
of MabCampath. 
 
In the event of serious infection or severe haematological toxicity MabCampath should be interrupted 
until the event resolves. It is recommended that MabCampath should be interrupted in patients whose 
platelet count falls to < 25,000/l or whose absolute neutrophil count (ANC) drops to < 250/l. 
MabCampath may be reinstituted after the infection or toxicity has resolved. MabCampath should be 
permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears. The 
following table outlines the recommended procedure for dose modification following the occurrence 
of haematological toxicity while on therapy: 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

4 
 

 
Haematologic values  Dose modification* 

ANC < 250/μl and/or platelet count ≤25,000/μl  

For first occurrence Withhold MabCampath therapy. Resume 
MabCampath at 30 mg when ANC ≥ 500/μl and 
platelet count ≥ 50,000/μl. 

For second occurrence Withhold MabCampath therapy. Resume 
MabCampath at 10 mg when ANC ≥ 500/μl and 
platelet count  ≥ 50,000/μl. 

For third occurrence Discontinue MabCampath therapy. 

≥ 50% decrease from baseline in patients initiating therapy with a baseline ANC ≤ 250/μl and/or a 
baseline platelet count ≤ 25,000/μl 

For first occurrence Withhold MabCampath therapy. Resume 
MabCampath at 30 mg upon return to baseline 
value(s). 

For second occurrence Withhold MabCampath therapy. Resume 
MabCampath at 10 mg upon return to baseline 
value(s). 

For third occurrence Discontinue MabCampath therapy. 
*If the delay between dosing is  7 days, initiate therapy at MabCampath 3 mg and escalate to 10 mg 
and then to 30 mg as tolerated 
 
 
Special populations 
 
Elderly (over 65 years of age) 
 
Recommendations are as stated above for adults. Patients should be monitored carefully (see 
section 4.4). 
 
Patients with renal or hepatic impairment 
 
No studies have been conducted.    
 
Paediatric population 
 
The safety and efficacy of MabCampath in children aged less than 17 years of age have not been 
established. No data are available.  
 
Method of administration  
 
The MabCampath solution must be prepared according to the instructions provided in section 6.6. All 
doses should be administered by intravenous infusion over approximately 2 hours. 
 
4.3 Contraindications 
 
- Hypersensitivity to alemtuzumab, to murine proteins or to any of the excipients.  
- Active systemic infections.  
- HIV.  
- Active second malignancies.  
- Pregnancy. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

5 
 

4.4 Special warnings and precautions for use 
 
Acute adverse reactions, which may occur during initial dose escalation and some of which may be 
due to the release of cytokines, include hypotension, chills/rigors, fever, shortness of breath and 
rashes. Additional reactions include nausea, urticaria, vomiting, fatigue, dyspnoea, headache, pruritus, 
diarrhoea and bronchospasm. The frequency of infusion reactions was highest in the first week of 
therapy, and declined in the second or third week of treatment, in patients treated with MabCampath 
both as first line therapy and in previously treated patients. 
 
If these events are moderate to severe, then dosing should continue at the same level prior to each dose 
escalation, with appropriate premedication, until each dose is well tolerated. If therapy is withheld for 
more than 7 days, MabCampath should be reinstituted with gradual dose escalation.  
 
Transient hypotension has occurred in patients receiving MabCampath. Caution should be used in 
treating patients with ischaemic heart disease, angina and/or in patients receiving an antihypertensive 
medicinal product. Myocardial infarction and cardiac arrest have been observed in association with 
MabCampath infusion in this patient population. 
 
Assessment and ongoing monitoring of cardiac function (e.g. echocardiography, heart rate and body 
weight) should be considered in patients previously treated with potentially cardiotoxic agents. 
 
It is recommended that patients be premedicated with oral or intravenous steroids 30 - 60 minutes 
prior to each MabCampath infusion during dose escalation and as clinically indicated.  Steroids may 
be discontinued as appropriate, once dose escalation has been achieved.  In addition, an oral 
antihistamine, e.g. diphenhydramine 50 mg, and an analgesic, e.g. paracetamol 500 mg, may be given.  
In the event that acute infusion reactions persist, the infusion time may be extended up to 8 hours from 
the time of reconstitution of MabCampath in solution for infusion. 
 
Profound lymphocyte depletion, an expected pharmacological effect of MabCampath, inevitably 
occurs and may be prolonged. CD4 and CD8 T-cell counts begin to rise from weeks 8-12 during 
treatment and continue to recover for several months following the discontinuation of treatment.  In 
patients receiving MabCampath as first line therapy, the recovery of CD4+ counts to ≥200 cells/µl 
occurred by 6 months post-treatment, however, at 2 months post-treatment the median was 183 
cells/l.  In previously treated patients receiving MabCampath, the median time to reach a level of 200 
cells/l is 2 months following last infusion with MabCampath but may take more than 12 months to 
approximate pretreatment levels. This may predispose patients to opportunistic infections. It is highly 
recommended that anti-infective prophylaxis (e.g. trimethoprim/sulfamethoxazole 1 tablet twice daily, 
3 times weekly, or other prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and an effective 
oral anti-herpes agent, such as famciclovir, 250 mg twice daily) should be initiated while on therapy 
and for a minimum of 2 months following completion of treatment with MabCampath or until the 
CD4+ count has recovered to 200 cells/l or greater, whichever is the later.  
 
The potential for an increased risk of infection-related complications may exist following treatment 
with multiple chemotherapeutic or biological agents. 
 
Because of the potential for Transfusion Associated Graft Versus Host Disease (TAGVHD) it is 
recommended that patients who have been treated with MabCampath receive irradiated blood 
products. 
 
Asymptomatic laboratory positive Cytomegalovirus (CMV) viraemia should not necessarily be 
considered a serious infection requiring interruption of therapy.  Ongoing clinical assessment should 
be performed for symptomatic CMV infection during MabCampath treatment and for at least 2 months 
following completion of treatment. 
 
Transient grade 3 or 4 neutropenia occurs very commonly by weeks 5-8 following initiation of 
treatment. Transient grade 3 or 4 thrombocytopenia occurs very commonly during the first 2 weeks of 
therapy and then begins to improve in most patients. Therefore, haematological monitoring of patients 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

6 
 

is indicated. If a severe haematological toxicity develops, MabCampath treatment should be 
interrupted until the event resolves. Treatment may be reinstituted following resolution of the 
haematological toxicity (see section 4.2). MabCampath should be permanently discontinued if 
autoimmune anaemia or autoimmune thrombocytopenia appears. 
 
Complete blood counts and platelet counts should be obtained at regular intervals during MabCampath 
therapy and more frequently in patients who develop cytopenias. 
 
It is not proposed that regular and systematic monitoring of CD52 expression should be carried out as 
routine clinical practice. However, if retreatment is considered, it may be prudent to confirm the 
presence of CD52 expression.  In data available from first line patients treated with MabCampath, loss 
of CD52 expression was not observed around the time of disease progression or death. 
 
Patients may have allergic or hypersensitivity reactions to MabCampath and to murine or chimeric 
monoclonal antibodies.  
 
Medicinal products for the treatment of hypersensitivity reactions, as well as preparedness to institute 
emergency measures in the event of reaction during administration is necessary (see section 4.2). 
 
Males and females of childbearing potential should use effective contraceptive measures during 
treatment and for 6 months following MabCampath therapy (see sections 4.6 and 5.3). 
 
No studies have been conducted which specifically address the effect of age on MabCampath 
disposition and toxicity. In general, older patients (over 65 years of age) tolerate cytotoxic therapy less 
well than younger individuals. Since CLL occurs commonly in this older age group, these patients 
should be monitored carefully (see section 4.2).  In the studies in first line and previously treated 
patients no substantial differences in safety and efficacy related to age were observed; however the 
sizes of the databases are limited. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Although no formal drug interaction studies have been performed with MabCampath, there are no 
known clinically significant interactions of MabCampath with other medicinal products.  Because 
MabCampath is a recombinant humanized protein, a P450 mediated drug-drug interaction would not 
be expected. However, it is recommended that MabCampath should not be given within 3 weeks of 
other chemotherapeutic agents.  
 
Although it has not been studied, it is recommended that patients should not receive live viral vaccines 
in, at least, the 12 months following MabCampath therapy. The ability to generate a primary or 
anamnestic humoral response to any vaccine has not been studied. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy  
 
MabCampath is contraindicated during pregnancy. Human IgG is known to cross the placental barrier; 
MabCampath may cross the placental barrier as well and thus potentially cause foetal B and T cell 
lymphocyte depletion. Animal reproduction studies have not been conducted with MabCampath. It is 
not known if MabCampath can cause foetal harm when administered to a pregnant woman.   
 
Males and females of childbearing capacity should use effective contraceptive measures during 
treatment and for 6 months following MabCampath therapy (see section 5.3). 
 
Lactation  
 
It is not known whether MabCampath is excreted in human milk. If treatment is needed, breast-feeding 
should be discontinued during treatment and for at least 4 weeks following MabCampath therapy. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

7 
 

 
Fertility 
 
There are no definitive studies of MabCampath which assess its impact on fertility. It is not known if 
MabCampath can affect human reproductive capacity (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. However, 
caution should be exercised as confusion and somnolence have been reported. 
 
4.8 Undesirable effects 
 
The tables below report adverse reactions by MedDRA system organ classes (MedDRA SOCs). The 
frequencies are based on clinical trial data.  
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and 
related conditions.   
 
The frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon 
(≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000). No information is 
available for events that occur at lower frequency, due to the size of the population studied; n=147 for 
first line treated patients and n=149 for previously treated patients. 
 
The most frequent adverse reactions with MabCampath are: infusion reactions (pyrexia, chills, 
hypotension, urticaria, nausea, rash, tachycardia, dyspnoea), cytopenias (neutropenia, lymphopenia, 
thrombocytopenia, anaemia), infections (CMV viraemia, CMV infection, other infections), 
gastrointestinal symptoms (nausea, emesis, abdominal pain), and neurological symptoms (insomnia, 
anxiety). The most frequent serious adverse reactions are cytopenias, infusion reactions, and 
immunosuppression/infections. 
 
Undesirable effects in first line patients 
 
Safety data in first-line B-CLL patients are based on adverse reactions that occurred on study in 147 
patients enrolled in a randomized, controlled study of MabCampath as a single agent administered at a 
dose of 30 mg intravenously three times weekly for up to 12 weeks, inclusive of dose escalation 
period.  Approximately 97% of first-line patients experienced adverse reactions; the most commonly 
reported reactions in first line patients usually occurred in the first week of therapy. 
 
Within each frequency grouping, undesirable effects observed during treatment or within 30 days 
following the completion of treatment with MabCampath are presented in order of decreasing 
seriousness. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

8 
 

 
System organ class 
 

Very common Common Uncommon 

Infections and 
infestations 

Cytomegalovirus 
viraemia  
Cytomegalovirus 
infection  
 

Pneumonia  
Bronchitis  
Pharyngitis 
Oral candidiasis  

Sepsis 
Staphylococcal 
bacteraemia 
Tuberculosis  
Bronchopneumonia  
Herpes ophthalmicus 
Beta haemolytic 
streptococcal infection  
Candidiasis  
Genital candidiasis  
Urinary tract infection 
Cystitis  
Body tinea  
Nasopharyngitis 
Rhinitis  

Blood and lymphatic 
system disorder 

 Febrile neutropenia  
Neutropenia  
Leukopenia  
Thrombocytopenia 
Anaemia 

Agranulocytosis  
Lymphopenia  
Lymphadenopathy 
Epistaxis  

Immune system 
disorders 

  Anaphylactic reaction 
Hypersensitivity 

Metabolism and 
nutrition disorders 

 Weight decreased  Tumour lysis syndrome 
Hyperglycaemia 
Protein total decreased 
Anorexia 

Psychiatric disorders  Anxiety   
Nervous system 
disorders 

 Syncope  
Dizziness  
Tremor 
Paraesthesia  
Hypoesthesia 
Headache 

Vertigo 

Eye disorders   Conjunctivitis  
Cardiac disorders   Cyanosis  

Bradycardia  
Tachycardia  
Sinus tachycardia 

Cardiac arrest  
Myocardial infarction  
Angina pectoris  
Atrial fibrillation 
Arrhythmia 
supraventricular 
Sinus bradycardia  
Supraventricular 
extrasystoles  

Vascular disorders Hypotension  Hypertension  Orthostatic hypotension  
Hot flush  
Flushing 

Respiratory, thoracic 
and mediastinal 
disorders 

 Bronchospasm  
Dyspnoea 

Hypoxia  
Pleural effusion  
Dysphonia 
Rhinorrhoea 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

9 
 

System organ class 
 

Very common Common Uncommon 

Gastrointestinal 
disorders 

Nausea  Vomiting  
Abdominal pain  

Ileus  
Oral discomfort 
Stomach discomfort 
Diarrhoea 

Skin and subcutaneous 
tissue disorders 

Urticaria  
Rash  

Dermatitis allergic  
Pruritus  
Hyperhidrosis 
Erythema 

Rash pruritic  
Rash macular  
Rash erythematous 
Dermatitis 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  
Musculoskeletal 
pain 
Back pain 

Bone pain  
Arthralgia  
Musculoskeletal chest 
pain  
Muscle spasms 

Renal and urinary 
disorders 

  Urine output decreased  
Dysuria 

General disorders and 
administration site 
conditions 

Fever 
Chills  

Fatigue 
Asthenia  

Mucosal inflammation  
Infusion site erythema  
Localised oedema  
Infusion site oedema  
Malaise 

 
Acute infusion reactions including fever, chills, nausea, vomiting, hypotension, fatigue, rash, urticaria, 
dyspnoea, headache, pruritus and diarrhoea have been reported. The majority of these reactions are 
mild to moderate in severity. Acute infusion reactions usually occur during the first week of therapy 
and substantially decline thereafter. Grade 3 or 4 infusion reactions are uncommon after the first week 
of therapy.  
 
Undesirable effects in previously treated patients 
 
Safety data in previously treated B-CLL patients are based on 149 patients enrolled in single-arm 
studies of MabCampath (Studies 1, 2, and 3). More than 80% of previously treated patients may be 
expected to experience adverse reactions; the most commonly reported reactions usually occur during 
the first week of therapy. 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

10 
 

System organ class 
 

Very common Common Uncommon 

Infections and 
infestations 

Sepsis 
Pneumonia 
Herpes simplex 

Cytomegalovirus 
infection 
Pneumocystis jiroveci 
infection  
Pneumonitis  
Fungal infection  
Candidiasis 
Herpes zoster 
Abscess  
Urinary tract infection 
Sinusitis  
Bronchitis  
Upper respiratory tract 
infection 
Pharyngitis  
Infection 

Bacterial infection  
Viral infection  
Fungal dermatitis 
Laryngitis 
Rhinitis 
Onychomycosis 

Neoplasms, benign, 
malignant and 
unspecified (incl. cysts 
and polyps) 

  Lymphoma – like 
disorder 

Blood and lymphatic 
system disorder 

Granulocytopenia 
Thrombocytopenia 
Anaemia 

Febrile neutropenia 
Pancytopenia 
Leukopenia  
Lymphopenia  
Purpura  

Aplasia bone marrow 
Disseminated 
intravascular 
coagulation  
Haemolytic anaemia, 
Decreased haptoglobin  
Bone marrow 
depression 
Epistaxis 
Gingival bleeding 
Haematology test 
abnormal 

Immune system 
disorders 

  Allergic reaction 

   Severe anaphylactic  
and other 
hypersensitivity 
reactions 

Metabolism and 
nutrition disorders 

Anorexia Hyponatraemia 
Hypocalcaemia  
Weight decrease 
Dehydration  
Thirst 

Hypokalaemia  
Diabetes mellitus 
aggravated  

Psychiatric disorders  Confusion 
Anxiety 
Depression  
Somnolence  
Insomnia 

Depersonalisation  
Personality disorder  
Abnormal thinking  
Impotence 
Nervousness  Me

dic
ina

l p
rod

uc
t n

o l
on

ge
r a

uth
ori

se
d



 

11 
 

Nervous system 
disorders 

Headache Vertigo  
Dizziness  
Tremor  
Paresthesia 
Hypoesthesia  
Hyperkinesia  
Taste loss  

Syncope 
Abnormal gait 
Dystonia 
Hyperesthesia 
Neuropathy 
Taste perversion 

Eye disorders  Conjunctivitis Endophthalmitis 
Ear and labyrinth 
disorders 

  Deafness 
Tinnitus 

Cardiac disorders   Palpitation  
Tachycardia  

Cardiac arrest 
Myocardial infarction 
Atrial fibrillation 
Supraventricular 
tachycardia 
Arrhythmia 
Bradycardia 
Abnormal ECG 

Vascular disorders Hypotension Hypertension 
Vasospasm 
Flushing 

Peripheral ischaemia  

Respiratory, thoracic 
and mediastinal  
disorders 

Dyspnoea Hypoxia 
Haemoptysis  
Bronchospasm 
Coughing  

Stridor 
Throat tightness  
Pulmonary infiltration  
Pleural effusion  
Breath sounds 
decreased  
Respiratory disorder  

Gastrointestinal 
disorders 

Vomiting  
Nausea  
Diarrhoea 

Gastrointestinal 
haemorrhage 
Ulcerative stomatitis  
Stomatitis 
Abdominal pain 
Dyspepsia  
Constipation  
Flatulence  

Gastroenteritis 
Tongue ulceration  
Gingivitis  
Hiccup  
Eructation 
Dry mouth  

Hepatobiliary disorders 
 

 Hepatic function 
abnormal 

 

Skin and subcutaneous 
tissue disorders 

Pruritus 
Urticaria 
Rash 
Hyperhidrosis 

Bullous eruption  
Erythematous rash  

Maculo-papular rash 
Skin disorder 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Myalgia  
Skeletal pain  
Back pain  

Leg pain 
Hypertonia 

Renal and urinary 
disorders 

  Haematuria 
Urinary incontinence  
Urine flow decreased  
Polyuria  
Renal function 
abnormal  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

12 
 

General disorders and 
administration site 
conditions 

Chills 
Fever 
Fatigue 

Chest pain 
Influenza-like 
symptoms 
Mucositis 
Oedema mouth  
Oedema  
Asthenia 
Malaise 
Temperature change 
sensation  
Infusion site reaction  
Pain  

Pulmonary oedema 
Peripheral oedema 
Periorbital oedema 
Mucosal ulceration 
Infusion site bruising 
Infusion site dermatitis 
Infusion site pain 

 
Undesirable effects observed during post-marketing surveillance  
 
Infusion reactions: Serious and sometimes fatal reactions, including bronchospasm, hypoxia, syncope, 
pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, myocardial 
infarction, arrhythmias, acute cardiac insufficiency and cardiac arrest have been observed. Severe 
anaphylactic and other hypersensitivity reactions, including anaphylactic shock and angioedema, have 
been reported following MabCampath administration. These symptoms can be ameliorated or avoided 
if premedication and dose escalation are utilised (see section 4.4).   
 
Infections and infestations: Serious and sometimes fatal viral (e.g. adenovirus, parainfluenza, hepatitis 
B, progressive multifocal leukoencephalopathy (PML)), bacterial (including tuberculosis and atypical 
mycobacterioses, nocardiosis), protozoan (e.g. toxoplasma gondii), and fungal (e.g. rhinocerebral 
mucormycosis) infections, including those due to reactivation of latent infections have occurred during 
post-marketing surveillance. The recommended anti-infective prophylaxis treatment appears to be 
effective in reducing the risk of PCP and herpes infections (see section 4.4).  
 
EBV-associated lymphoproliferative disorders, in some cases fatal, have been reported. 
 
Blood and lymphatic system disorders:  Severe bleeding reactions have been reported.  
 
Immune system disorders:  Serious and sometimes fatal autoimmune phenomena including 
autoimmune haemolytic anaemia, autoimmune thrombocytopenia, aplastic anaemia, Guillain Barré 
syndrome and its chronic form, chronic inflammatory demyelinating polyradiculoneuropathy have 
been reported.  A positive Coombs test has also been observed.  Fatal Transfusion Associated Graft 
Versus Host Disease (TAGVHD) has also been reported. 
 
Metabolism and nutritional disorders:  Tumour lysis syndrome with fatal outcome has been reported.  
 
Nervous system disorders:  Intracranial haemorrhage has occurred with fatal outcome, in patients with 
thrombocytopenia. 
 
Cardiac disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction have 
been reported in patients previously treated with potentially cardiotoxic agents. 
 
4.9 Overdose 
 
Patients have received repeated unit doses of up to 240 mg of MabCampath. The frequency of grade 3 
or 4 adverse events, such as fever, hypotension and anaemia, may be higher in these patients. There is 
no known specific antidote for MabCampath. Treatment consists of discontinuation of MabCampath 
and supportive therapy. 
 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

13 
 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC04. 
 
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 
21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal 
and malignant peripheral blood B and T cell lymphocytes. Alemtuzumab was generated by the 
insertion of six complementarity-determining regions from an IgG2a rat monoclonal antibody into a 
human IgG1 immunoglobulin molecule. 
 
Alemtuzumab causes the lysis of lymphocytes by binding to CD52, a highly expressed, non-
modulating antigen which is present on the surface of essentially all B and T cell lymphocytes as well 
as monocytes, thymocytes and macrophages. The antibody mediates the lysis of lymphocytes via 
complement fixation and antibody-dependent cell mediated cytotoxicity. The antigen has been found 
on a small percentage (< 5%) of granulocytes, but not on erythrocytes or platelets. Alemtuzumab does 
not appear to damage haematopoietic stem cells or progenitor cells. 

First line B-CLL patients  

The safety and efficacy of MabCampath  were evaluated in a Phase 3, open-label, randomized 
comparative trial of first line (previously untreated) Rai stage I-IV B-CLL patients requiring therapy 
(Study 4).  MabCampath was shown to be superior to chlorambucil as measured by the primary 
endpoint progression free survival (PFS) (see Figure 1).  
 

Figure 1:  Progression free survival in first line study (by treatment group) 
 

 
 
The secondary objectives included complete response (CR) and overall response (CR or partial 
response) rates using the 1996 NCIWG criteria, the duration of response, time to alternative treatment 
and safety of the two treatment arms.   
 Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

14 
 

Summary of first-line patient population and outcomes  
 
 Independent review of response rate and duration 
 MabCampath 

n=149 
Chlorambucil 
n=148 

P value 

Median Age (Years) 59 60 Not Applicable 
Rai Stage III/IV Disease 33.6% 33.1% Not Applicable 

Overall Response Rate 83.2% 55.4% <0.0001* 
Complete Response 24.2% 2.0% <0.0001* 
MRD negative**** 7.4% 0.0% 0.0008* 
Partial Response 59.1% 53.4% Not Applicable 
Duration of Response**, CR or 
PR (Months)  
K-M median (95% Confidence 
Interval) 

N=124 
16.2  

(11.5, 23.0) 

N=82 
12.7 

(10.2, 14.3)  

Not Applicable 

Time to Alternative Treatment 
(Months) 
K-M median (95% Confidence 
Interval) 

23.3  
(20.7, 31.0) 

14.7  
(12.6, 16.8) 

0.0001*** 

*Pearson chi-square test or Exact test 
** Duration of best response 
*** log-rank test stratified by Rai group (Stage I-II vs III-IV) 
**** by 4-colour flow  

 
Cytogenetic analyses in first line B-CLL patients:  
 
The cytogenetic profile of B-CLL has been increasingly recognized as providing important prognostic 
information and may predict response to certain therapies. Of the first-line patients (n=282) in whom 
baseline cytogenetic (FISH) data were available in Study 4, chromosomal aberrations were detected in 
82%, while normal karyotype was detected in 18%. Chromosomal aberrations were categorized 
according to Döhner’s hierarchical model.  In first line patients, treated with either MabCampath or 
chlorambucil, there were 21 patients with the 17p deletion, 54 patients with 11q deletion, 34 patients 
with trisomy 12, 51 patients with normal karyotype and 67 patients with sole 13q deletion.  
  
ORR was superior in patients with any 11q deletion (87% v 29%; p<0.0001) or sole deletion 13q (91% 
v 62%; p=0.0087) treated with MabCampath compared to chlorambucil. A trend toward improved 
ORR was observed in patients with 17p deletion treated with MabCampath (64% v 20%; p=0.0805). 
Complete remissions were also superior in patients with sole 13q deletion treated with MabCampath 
(27% v 0%; p=0.0009). Median PFS was superior in patients with sole 13q deletion treated with 
MabCampath (24.4 v 13.0 months; p=0.0170 stratified by Rai Stage). A trend towards improved PFS 
was observed in patients with 17p deletion, trisomy 12 and normal karyotype, which did not reach 
significance due to small sample size. 
 
Assessment of CMV by PCR:  
 
In the randomized controlled trial in first line patients (Study 4), patients in the MabCampath arm were 
tested weekly for CMV using a PCR (polymerase chain reaction) assay from initiation through 
completion of therapy, and every 2 weeks for the first 2 months following therapy.  In this study, 
asymptomatic positive PCR only for CMV was reported in 77/147 (52.4%) of MabCampath-treated 
patients; symptomatic CMV infection was reported less commonly in 23/147 MabCampath treated 
patients (16%).  In the MabCampath arm 36/77 (46.8%) of patients with asymptomatic PCR positive 
CMV received antiviral therapy and 47/77 (61%) of these patients had MabCampath therapy 
interrupted.  The presence of asymptomatic positive PCR for CMV or symptomatic PCR positive 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

15 
 

CMV infection during treatment with MabCampath had no measurable impact on progression free 
survival (PFS). 
 
Previously treated B-CLL patients: 
 
Determination of the efficacy of MabCampath is based on overall response and survival rates. Data 
available from three uncontrolled B-CLL studies are summarised in the following table: 
 

Efficacy parameters Study 1 Study 2 Study 3 
Number of Patients 93 32 24 
Diagnostic Group B-CLL pts who had 

received an alkylating 
agent and had failed 

fludarabine 

B-CLL pts who had 
failed to respond or 
relapsed following 

treatment with 
conventional 
chemotherapy 

B-CLL (plus a PLL) 
pts who had failed to 
respond or relapsed 
following treatment 

with fludarabine 

Median Age (years) 66 57 62 
Disease Characteristics (%) 
     Rai Stage III/IV 
     B Symptoms 

 
76 
42 

 
72 
31 

 
71 
21 

Prior Therapies (%): 
     Alkylating Agents 
     Fludarabine 

 
100 
100 

 
100 
34 

 
92 

100 
Number of Prior Regimens (range) 3 (2-7) 3 (1-10)  3 (1-8) 
Initial Dosing Regimen Gradual escalation 

from 3 to 10 to 30 mg 
Gradual escalation 
from 10 to 30 mg 

Gradual escalation 
from 10 to 30 mg 

Final Dosing Regimen 30 mg iv 3 x weekly 30 mg iv 3 x weekly 30 mg iv 3 x weekly 
Overall Response Rate (%) 
(95% Confidence Interval) 
     Complete Response 
     Partial Response 

33  
 (23-43) 

2 
31 

21  
(8-33) 

0 
21 

29  
(11-47) 

0 
29 

Median Duration of Response (months) 
(95% Confidence Interval) 

7  
(5-8) 

7 
 (5-23) 

11  
(6-19) 

Median time to Response (months) 
(95% Confidence Interval) 

2  
(1-2) 

4  
(1-5) 

4 
 (2-4) 

Progression-Free Survival (months)  
(95% Confidence Interval) 

4  
(3-5) 

5  
(3-7) 

7  
(3-9) 

Survival (months): 
(95% Confidence Interval) 
     All patients 
     Responders 

 
 

16 (12-22) 
33 (26-NR) 

 
 

26 (12-44) 
44 (28-NR) 

 
 

28 (7-33) 
36 (19-NR) 

NR = not reached 
 
5.2 Pharmacokinetic properties 
 
Pharmacokinetics were characterised in MabCampath-naive patients with B-cell chronic lymphocytic 
leukaemia (B-CLL) who had failed previous therapy with purine analogues. MabCampath was 
administered as a 2 hour intravenous infusion, at the recommended dosing schedule, starting at 3 mg 
and increasing to 30 mg, 3 times weekly, for up to 12 weeks. MabCampath pharmacokinetics followed 
a 2-compartment model and displayed non-linear elimination kinetics.  After the last 30 mg dose, the 
median volume of distribution at steady-state was 0.15 l/kg (range: 0.1-0.4 l/kg), indicating that 
distribution was primarily to the extracellular fluid and plasma compartments. Systemic clearance 
decreased with repeated administration due to decreased receptor-mediated clearance (i.e. loss of 
CD52 receptors in the periphery). With repeated administration and consequent plasma concentration 
accumulation, the rate of elimination approached zero-order kinetics. As such, half-life was 8 hours 
(range: 2-32 hours) after the first 30 mg dose and was 6 days (range: 1-14 days) after the last 30 mg 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

16 
 

dose.  Steady-state concentrations were reached after about 6 weeks of dosing. No apparent difference 
in pharmacokinetics between males and females was observed nor was any apparent age effect 
observed. 
 
5.3 Preclinical safety data 
 
Preclinical evaluation of alemtuzumab in animals has been limited to the cynomolgus monkey because 
of the lack of expression of the CD52 antigen on non-primate species. 
 
Lymphocytopenia was the most common treatment-related effect in this species. A slight cumulative 
effect on the degree of lymphocyte depletion was seen in repeated dose studies compared to single 
dose studies. Lymphocyte depletion was rapidly reversible after cessation of dosing. Reversible 
neutropenia was seen following daily intravenous or subcutaneous dosing for 30 days, but not 
following single doses or daily dosing for 14 days. Histopathology results from bone marrow samples 
revealed no remarkable changes attributable to treatment. Single intravenous doses of 10 and 30 mg/kg 
produced moderate to severe dose related hypotension accompanied by a slight tachycardia. 
 
MabCampath Fab binding was observed in lymphoid tissues and the mononuclear phagocyte system.  
Significant Fab binding was also observed in the male reproductive tract (epididymis, sperm, seminal 
vesicle) and the skin. 
 
No other findings, in the above toxicity studies, provide information of significant relevance to clinical 
use. 
 
No short or long term animal studies have been conducted with MabCampath to assess carcinogenic 
and mutagenic potential.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium edetate  
Polysorbate 80 
Potassium chloride 
Potassium dihydrogen phosphate 
Sodium chloride 
Dibasic sodium phosphate 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.  
 
There are no known incompatibilities with other medicinal products. However, other medicinal 
products should not be added to the MabCampath infusion or simultaneously infused through the same 
intravenous line. 
 
6.3 Shelf life 
 
Unopen ampoule: 3 years. 
 
Reconstituted solution: MabCampath contains no antimicrobial preservative. MabCampath should be 
used within 8 hours after dilution. Solutions may be stored at 15C-30C or refrigerated. This can only 
be accepted if preparation of the solution takes place under strictly aseptic conditions and the solution 
is protected from light. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

17 
 

 
6.4 Special precautions for storage 
 
Store in a refrigerator (2C-8C).  
Do not freeze. 
Store in the original package in order to protect from light. 
 
For storage conditions of the reconstituted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Clear Type I glass ampoule, containing 3 ml of concentrate.  
Pack size: carton of 3 ampoules. 
 
6.6 Special precautions for disposal and other handling 
 
The ampoule contents should be inspected for particulate matter and discolouration prior to 
administration. If particulate matter is present or the concentrate is coloured, then the ampoule should 
not be used. 
 
MabCampath contains no antimicrobial preservatives, therefore, it is recommended that MabCampath 
should be prepared for intravenous infusion using aseptic techniques and that the diluted solution for 
infusion should be administered within 8 hours after preparation and protected from light. The 
required amount of the ampoule contents should be added, via a sterile, low-protein binding, non-fibre 
5 μm filter, to 100 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose (5%) 
solution for infusion. The bag should be inverted gently to mix the solution. Care should be taken to 
ensure the sterility of the prepared solution particularly as it contains no antimicrobial preservatives.  
 
Other medicinal products should not be added to the MabCampath infusion solution or simultaneously 
infused through the same intravenous line (see section 4.5). 
 
Caution should be exercised in the handling and preparation of the MabCampath solution. The use of 
latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the ampoule 
or other accidental spillage. Women who are pregnant or trying to become pregnant should not handle 
MabCampath.  
 
Procedures for proper handling and disposal should be observed. Any spillage or waste material 
should be disposed of by incineration.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe BV 
Gooimeer 10 
1411 DD Naarden 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/01/193/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 06/07/2001 
Date of latest renewal: 10/07/2011 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

18 
 

 
 
10. DATE OF REVISION OF THE TEXT 
 

 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu. 
 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

19 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
MabCampath 30 mg/ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One ml contains 30 mg of alemtuzumab. 
Each vial contains 30 mg of alemtuzumab. 
 
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 
21-28 kD lymphocyte cell surface glycoprotein (CD52). The antibody is produced in mammalian cell 
(Chinese Hamster Ovary) suspension culture in a nutrient medium. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
Colourless to slightly yellow concentrate. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
MabCampath is indicated for the treatment of patients with B-cell chronic lymphocytic leukaemia (B-
CLL) for whom fludarabine combination chemotherapy is not appropriate.  
 
4.2 Posology and method of administration 
 
MabCampath should be administered under the supervision of a physician experienced in the use of 
cancer therapy.   
 
Posology 
 
During the first week of treatment, MabCampath should be administered in escalating doses: 3 mg on 
day 1, 10 mg on day 2 and 30 mg on day 3 assuming that each dose is well tolerated. Thereafter, the 
recommended dose is 30 mg daily administered 3 times weekly on alternate days up to a maximum of 
12 weeks.  
 
In most patients, dose escalation to 30 mg can be accomplished in 3-7 days. However, if acute 
moderate to severe adverse reactions such as hypotension, rigors, fever, shortness of breath, chills, 
rashes and bronchospasm (some of which may be due to cytokine release) occur at either the 3 mg or 
10 mg dose levels, then those doses should be repeated daily until they are well tolerated before 
further dose escalation is attempted (see section 4.4). 
 
Median duration of treatment was 11.7 weeks for first-line patients and 9.0 weeks for previously 
treated patients.  
 
Once a patient meets all laboratory and clinical criteria for a complete response, MabCampath should 
be discontinued and the patient monitored. If a patient improves (i.e. achieves a partial response or 
stable disease) and then reaches a plateau without further improvement for 4 weeks or more, then 
MabCampath should be discontinued and the patient monitored. Therapy should be discontinued if 
there is evidence of disease progression. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

20 
 

 
Concomitant medicinal products 
 
Premedications 
 
Patients should be premedicated with oral or intravenous steroids, an appropriate antihistamine and 
analgesic 30-60 minutes prior to each MabCampath infusion during dose escalation and as clinically 
indicated thereafter (see section 4.4). 
 
Prophylactic antibiotics 
 
Antibiotics and antivirals should be administered routinely to all patients throughout and following 
treatment (see section 4.4).  
 
Dose modification guidelines 
 
There are no dose modifications recommended for severe lymphopenia given the mechanism of action 
of MabCampath. 
 
In the event of serious infection or severe haematological toxicity MabCampath should be interrupted 
until the event resolves. It is recommended that MabCampath should be interrupted in patients whose 
platelet count falls to < 25,000/l or whose absolute neutrophil count (ANC) drops to < 250/l. 
MabCampath may be reinstituted after the infection or toxicity has resolved. MabCampath should be 
permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears. The 
following table outlines the recommended procedure for dose modification following the occurrence 
of haematological toxicity while on therapy: 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

21 
 

 
Haematologic values  Dose modification* 

ANC < 250/μl and/or platelet count ≤25,000/μl  

For first occurrence Withhold MabCampath therapy. Resume 
MabCampath at 30 mg when ANC ≥ 500/μl and 
platelet count ≥ 50,000/μl. 

For second occurrence Withhold MabCampath therapy. Resume 
MabCampath at 10 mg when ANC ≥ 500/μl and 
platelet count  ≥ 50,000/μl. 

For third occurrence Discontinue MabCampath therapy. 

≥ 50% decrease from baseline in patients initiating therapy with a baseline ANC ≤ 250/μl and/or a 
baseline platelet count ≤ 25,000/μl 

For first occurrence Withhold MabCampath therapy. Resume 
MabCampath at 30 mg upon return to baseline 
value(s). 

For second occurrence Withhold MabCampath therapy. Resume 
MabCampath at 10 mg upon return to baseline 
value(s). 

For third occurrence Discontinue MabCampath therapy. 
*If the delay between dosing is  7 days, initiate therapy at MabCampath 3 mg and escalate to 10 mg 
and then to 30 mg as tolerated 
 
Special populations 
 
Elderly (over 65 years of age) 
 
Recommendations are as stated above for adults. Patients should be monitored carefully (see 
section 4.4). 
 
Patients with renal or hepatic impairment 
 
No studies have been conducted. 
 
Paediatric population 
 
The safety and efficacy of MabCampath in children aged less than 17 years of age have not been 
established. No data are available.  
 
Method of administration  
 
The MabCampath solution must be prepared according to the instructions provided in section 6.6. All 
doses should be administered by intravenous infusion over approximately 2 hours. 
 
4.3 Contraindications 
 
- Hypersensitivity to alemtuzumab, to murine proteins or to any of the excipients.  
- Active systemic infections.  
- HIV.  
- Active second malignancies.  
- Pregnancy. 
 
4.4 Special warnings and precautions for use 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

22 
 

 
Acute adverse reactions, which may occur during initial dose escalation and some of which may be 
due to the release of cytokines, include hypotension, chills/rigors, fever, shortness of breath and 
rashes.  Additional reactions include nausea, urticaria, vomiting, fatigue, dyspnoea, headache, pruritus, 
diarrhoea and bronchospasm.  The frequency of infusion reactions was highest in the first week of 
therapy, and declined in the second or third week of treatment, in patients treated with MabCampath 
both as first line therapy and in previously treated patients. 
 
If these events are moderate to severe, then dosing should continue at the same level prior to each dose 
escalation, with appropriate premedication, until each dose is well tolerated. If therapy is withheld for 
more than 7 days, MabCampath should be reinstituted with gradual dose escalation.  
 
Transient hypotension has occurred in patients receiving MabCampath. Caution should be used in 
treating patients with ischaemic heart disease, angina and/or in patients receiving an antihypertensive 
medicinal product. Myocardial infarction and cardiac arrest have been observed in association with 
MabCampath infusion in this patient population. 
 
Assessment and ongoing monitoring of cardiac function (e.g. echocardiography, heart rate and body 
weight) should be considered in patients previously treated with potentially cardiotoxic agents. 
 
It is recommended that patients be premedicated with oral or intravenous steroids 30 - 60 minutes 
prior to each MabCampath infusion during dose escalation and as clinically indicated. Steroids may be 
discontinued as appropriate, once dose escalation has been achieved. In addition, an oral antihistamine, 
e.g. diphenhydramine 50 mg, and an analgesic, e.g. paracetamol 500 mg, may be given.  In the event 
that acute infusion reactions persist, the infusion time may be extended up to 8 hours from the time of 
reconstitution of MabCampath in solution for infusion. 
 
Profound lymphocyte depletion, an expected pharmacological effect of MabCampath, inevitably 
occurs and may be prolonged. CD4 and CD8 T-cell counts begin to rise from weeks 8-12 during 
treatment and continue to recover for several months following the discontinuation of treatment.  In 
patients receiving MabCampath as first line therapy, the recovery of CD4+ counts to ≥200 cells/µl 
occurred by 6 months post-treatment, however, at 2 months post-treatment the median was 183 
cells/l.  In previously treated patients receiving MabCampath, the median time to reach a level of 200 
cells/l is 2 months following last infusion with MabCampath but may take more than 12 months to 
approximate pretreatment levels. This may predispose patients to opportunistic infections. It is highly 
recommended that anti-infective prophylaxis (e.g. trimethoprim/sulfamethoxazole 1 tablet twice daily, 
3 times weekly, or other prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and an effective 
oral anti-herpes agent, such as famciclovir, 250 mg twice daily) should be initiated while on therapy 
and for a minimum of 2 months following completion of treatment with MabCampath or until the 
CD4+ count has recovered to 200 cells/l or greater, whichever is the later.  
 
The potential for an increased risk of infection-related complications may exist following treatment 
with multiple chemotherapeutic or biological agents. 
 
Because of the potential for Transfusion Associated Graft Versus Host Disease (TAGVHD) it is 
recommended that patients who have been treated with MabCampath receive irradiated blood 
products. 
 
Asymptomatic laboratory positive Cytomegalovirus (CMV) viraemia should not necessarily be 
considered a serious infection requiring interruption of therapy. Ongoing clinical assessment should be 
performed for symptomatic CMV infection during MabCampath treatment and for at least 2 months 
following completion of treatment. 
 
Transient grade 3 or 4 neutropenia occurs very commonly by weeks 5-8 following initiation of 
treatment. Transient grade 3 or 4 thrombocytopenia occurs very commonly during the first 2 weeks of 
therapy and then begins to improve in most patients. Therefore, haematological monitoring of patients 
is indicated. If a severe haematological toxicity develops, MabCampath treatment should be 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

23 
 

interrupted until the event resolves. Treatment may be reinstituted following resolution of the 
haematological toxicity (see section 4.2). MabCampath should be permanently discontinued if 
autoimmune anaemia or autoimmune thrombocytopenia appears. 
 
Complete blood counts and platelet counts should be obtained at regular intervals during MabCampath 
therapy and more frequently in patients who develop cytopenias. 
 
It is not proposed that regular and systematic monitoring of CD52 expression should be carried out as 
routine clinical practice. However, if retreatment is considered, it may be prudent to confirm the 
presence of CD52 expression.  In data available from first line patients treated with MabCampath, loss 
of CD52 expression was not observed around the time of disease progression or death. 
 
Patients may have allergic or hypersensitivity reactions to MabCampath and to murine or chimeric 
monoclonal antibodies.  
 
Medicinal products for the treatment of hypersensitivity reactions, as well as preparedness to institute 
emergency measures in the event of reaction during administration is necessary (see section 4.2). 
 
Males and females of childbearing potential should use effective contraceptive measures during 
treatment and for 6 months following MabCampath therapy (see sections 4.6 and 5.3).  
 
No studies have been conducted which specifically address the effect of age on MabCampath 
disposition and toxicity. In general, older patients (over 65 years of age) tolerate cytotoxic therapy less 
well than younger individuals. Since CLL occurs commonly in this older age group, these patients 
should be monitored carefully (see section 4.2).  In the studies in first line and previously treated 
patients no substantial differences in safety and efficacy related to age were observed; however the 
sizes of the databases are limited.   
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Although no formal drug interaction studies have been performed with MabCampath, there are no 
known clinically significant interactions of MabCampath with other medicinal products.  Because 
MabCampath is a recombinant humanized protein, a P450 mediated drug-drug interaction would not 
be expected. However, it is recommended that MabCampath should not be given within 3 weeks of 
other chemotherapeutic agents.  
 
Although it has not been studied, it is recommended that patients should not receive live viral vaccines 
in, at least, the 12 months following MabCampath therapy. The ability to generate a primary or 
anamnestic humoral response to any vaccine has not been studied. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy  
 
MabCampath is contraindicated during pregnancy. Human IgG is known to cross the placental barrier; 
MabCampath may cross the placental barrier as well and thus potentially cause foetal B and T cell 
lymphocyte depletion. Animal reproduction studies have not been conducted with MabCampath. It is 
not known if MabCampath can cause foetal harm when administered to a pregnant woman. 
 
Males and females of childbearing capacity should use effective contraceptive measures during 
treatment and for 6 months following MabCampath therapy (see section 5.3). 
 
Lactation  
 
It is not known whether MabCampath is excreted in human milk. If treatment is needed, breast-feeding 
should be discontinued during treatment and for at least 4 weeks following MabCampath therapy. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

24 
 

Fertility 
 
There are no definitive studies of MabCampath which assess its impact on fertility. It is not known if 
MabCampath can affect human reproductive capacity (see section 5.3).   
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. However, 
caution should be exercised as confusion and somnolence have been reported. 
 
4.8 Undesirable effects 
 
The tables below report adverse reactions by MedDRA system organ classes (MedDRA SOCs). The 
frequencies are based on clinical trial data.  
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and 
related conditions.   
 
The frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon 
(≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000). No information is 
available for events that occur at lower frequency, due to the size of the population studied; n=147 for 
first line treated patients and n=149 for previously treated patients.     
 
The most frequent adverse reactions with MabCampath are: infusion reactions (pyrexia, chills, 
hypotension, urticaria, nausea, rash, tachycardia, dyspnoea), cytopenias (neutropenia, lymphopenia, 
thrombocytopenia, anaemia), infections (CMV viraemia, CMV infection, other infections), 
gastrointestinal symptoms (nausea, emesis, abdominal pain), and neurological symptoms (insomnia, 
anxiety). The most frequent serious adverse reactions are cytopenias, infusion reactions, and 
immunosuppression/infections. 
 
Undesirable effects in first line patients 
 
Safety data in first-line B-CLL patients are based on adverse reactions that occurred on study in 147 
patients enrolled in a randomized, controlled study of MabCampath as a single agent administered at a 
dose of 30 mg intravenously three times weekly for up to 12 weeks, inclusive of dose escalation 
period.  Approximately 97% of first-line patients experienced adverse reactions; the most commonly 
reported reactions in first line patients usually occurred in the first week of therapy.   
 
Within each frequency grouping, undesirable effects observed during treatment or within 30 days 
following the completion of treatment with MabCampath are presented in order of decreasing 
seriousness. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

25 
 

 
System organ class 
 

Very common Common Uncommon 

Infections and 
infestations 

Cytomegalovirus 
viraemia  
Cytomegalovirus 
infection  
 

Pneumonia  
Bronchitis  
Pharyngitis 
Oral candidiasis  

Sepsis 
Staphylococcal 
bacteraemia 
Tuberculosis  
Bronchopneumonia  
Herpes ophthalmicus 
Beta haemolytic 
streptococcal infection  
Candidiasis  
Genital candidiasis  
Urinary tract infection 
Cystitis  
Body tinea  
Nasopharyngitis 
Rhinitis  

Blood and lymphatic 
system disorder 

 Febrile neutropenia  
Neutropenia  
Leukopenia  
Thrombocytopenia 
Anaemia 

Agranulocytosis  
Lymphopenia  
Lymphadenopathy 
Epistaxis  

Immune system 
disorders 

  Anaphylactic reaction 
Hypersensitivity 

Metabolism and 
nutrition disorders 

 Weight decreased  Tumour lysis syndrome 
Hyperglycaemia 
Protein total decreased 
Anorexia 

Psychiatric disorders  Anxiety   
Nervous system 
disorders 

 Syncope  
Dizziness  
Tremor 
Paraesthesia  
Hypoesthesia 
Headache 

Vertigo 

Eye disorders   Conjunctivitis  
Cardiac disorders   Cyanosis  

Bradycardia  
Tachycardia  
Sinus tachycardia 

Cardiac arrest  
Myocardial infarction  
Angina pectoris  
Atrial fibrillation 
Arrhythmia 
supraventricular 
Sinus bradycardia  
Supraventricular 
extrasystoles  

Vascular disorders Hypotension  Hypertension  Orthostatic hypotension  
Hot flush  
Flushing 

Respiratory, thoracic 
and mediastinal  
disorders 

 Bronchospasm  
Dyspnoea 

Hypoxia  
Pleural effusion  
Dysphonia 
Rhinorrhoea 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

26 
 

System organ class 
 

Very common Common Uncommon 

Gastrointestinal 
disorders 

Nausea  Vomiting  
Abdominal pain  

Ileus  
Oral discomfort 
Stomach discomfort 
Diarrhoea 

Skin and subcutaneous 
tissue disorders 

Urticaria  
Rash  

Dermatitis allergic  
Pruritus  
Hyperhidrosis 
Erythema 

Rash pruritic  
Rash macular  
Rash erythematous 
Dermatitis 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  
Musculoskeletal 
pain 
Back pain 

Bone pain  
Arthralgia  
Musculoskeletal chest 
pain  
Muscle spasms 

Renal and urinary 
disorders 

  Urine output decreased  
Dysuria 

General disorders and 
administration site 
conditions 

Fever 
Chills  

Fatigue 
Asthenia  

Mucosal inflammation  
Infusion site erythema  
Localised oedema  
Infusion site oedema  
Malaise 

 
Acute infusion reactions including fever, chills, nausea, vomiting, hypotension, fatigue, rash, urticaria, 
dyspnoea, headache, pruritus and diarrhoea have been reported. The majority of these reactions are 
mild to moderate in severity. Acute infusion reactions usually occur during the first week of therapy 
and substantially decline thereafter. Grade 3 or 4 infusion reactions are uncommon after the first week 
of therapy.  
 
Undesirable effects in previously treated patients 
 
Safety data in previously treated B-CLL patients are based on 149 patients enrolled in single-arm 
studies of MabCampath (Studies 1, 2, and 3). More than 80% of previously treated patients may be 
expected to experience adverse reactions; the most commonly reported reactions usually occur during 
the first week of therapy.  
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

27 
 

System organ class 
 

Very common Common Uncommon 

Infections and 
infestations 

Sepsis 
Pneumonia 
Herpes simplex 

Cytomegalovirus 
infection 
Pneumocystis jiroveci 
infection  
Pneumonitis  
Fungal infection  
Candidiasis 
Herpes zoster 
Abscess  
Urinary tract infection 
Sinusitis  
Bronchitis  
Upper respiratory tract 
infection 
Pharyngitis  
Infection 

Bacterial infection  
Viral infection  
Fungal dermatitis 
Laryngitis 
Rhinitis 
Onychomycosis 

Neoplasms, benign, 
malignant and 
unspecified (incl. cysts 
and polyps) 

  Lymphoma – like 
disorder 

Blood and lymphatic 
system disorder 

Granulocytopenia 
Thrombocytopenia 
Anaemia 

Febrile neutropenia 
Pancytopenia 
Leukopenia  
Lymphopenia  
Purpura  

Aplasia bone marrow 
Disseminated 
intravascular 
coagulation  
Haemolytic anaemia, 
Decreased haptoglobin  
Bone marrow 
depression 
Epistaxis 
Gingival bleeding 
Haematology test 
abnormal 

Immune system 
disorders 

  Allergic reaction 

   Severe anaphylactic  
and other 
hypersensitivity 
reactions 

Metabolism and 
nutrition disorders 

Anorexia Hyponatraemia 
Hypocalcaemia  
Weight decrease 
Dehydration  
Thirst 

Hypokalaemia  
Diabetes mellitus 
aggravated  

Psychiatric disorders  Confusion 
Anxiety 
Depression  
Somnolence  
Insomnia 

Depersonalisation  
Personality disorder  
Abnormal thinking  
Impotence 
Nervousness  Me

dic
ina

l p
rod

uc
t n

o l
on

ge
r a

uth
ori

se
d



 

28 
 

Nervous system 
disorders 

Headache Vertigo  
Dizziness  
Tremor  
Paresthesia 
Hypoesthesia  
Hyperkinesia  
Taste loss  

Syncope 
Abnormal gait 
Dystonia 
Hyperesthesia 
Neuropathy 
Taste perversion 

Eye disorders  Conjunctivitis Endophthalmitis 
Ear and labyrinth 
disorders 

  Deafness 
Tinnitus 

Cardiac disorders   Palpitation  
Tachycardia  

Cardiac arrest 
Myocardial infarction 
Atrial fibrillation 
Supraventricular 
tachycardia 
Arrhythmia 
Bradycardia 
Abnormal ECG 

Vascular disorders Hypotension Hypertension 
Vasospasm 
Flushing 

Peripheral ischaemia  

Respiratory, thoracic 
and mediastinal  
disorders 

Dyspnoea Hypoxia 
Haemoptysis  
Bronchospasm 
Coughing  

Stridor 
Throat tightness  
Pulmonary infiltration  
Pleural effusion  
Breath sounds 
decreased  
Respiratory disorder  

Gastrointestinal 
disorders 

Vomiting  
Nausea  
Diarrhoea 

Gastrointestinal 
haemorrhage 
Ulcerative stomatitis  
Stomatitis 
Abdominal pain 
Dyspepsia  
Constipation  
Flatulence  

Gastroenteritis 
Tongue ulceration  
Gingivitis  
Hiccup  
Eructation 
Dry mouth  

Hepatobiliary disorders 
 

 Hepatic function 
abnormal 

 

Skin and subcutaneous 
tissue disorders 

Pruritus 
Urticaria 
Rash 
Hyperhidrosis 

Bullous eruption  
Erythematous rash  

Maculo-papular rash 
Skin disorder 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Myalgia  
Skeletal pain  
Back pain  

Leg pain 
Hypertonia 

Renal and urinary 
disorders 

  Haematuria 
Urinary incontinence  
Urine flow decreased  
Polyuria  
Renal function 
abnormal  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

29 
 

General disorders and 
administration site 
conditions 

Chills 
Fever 
Fatigue 

Chest pain 
Influenza-like 
symptoms 
Mucositis 
Oedema mouth  
Oedema  
Asthenia 
Malaise 
Temperature change 
sensation  
Infusion site reaction  
Pain  

Pulmonary oedema 
Peripheral oedema 
Periorbital oedema 
Mucosal ulceration 
Infusion site bruising 
Infusion site dermatitis 
Infusion site pain 

 
Undesirable effects observed during post-marketing surveillance  
 
Infusion reactions: Serious and sometimes fatal reactions, including bronchospasm, hypoxia, syncope, 
pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, myocardial 
infarction, arrhythmias, acute cardiac insufficiency and cardiac arrest have been observed. Severe 
anaphylactic and other hypersensitivity reactions, including anaphylactic shock and angioedema, have 
been reported following MabCampath administration. These symptoms can be ameliorated or avoided 
if premedication and dose escalation are utilised (see section 4.4). 
 
Infections and infestations:  Serious and sometimes fatal viral (e.g. adenovirus, parainfluenza, hepatitis 
B, progressive multifocal leukoencephalopathy (PML)), bacterial (including tuberculosis and atypical 
mycobacterioses, nocardiosis), protozoan (e.g. toxoplasma gondii), and fungal (e.g. rhinocerebral 
mucormycosis) infections, including those due to reactivation of latent infections have occurred during 
post-marketing surveillance. The recommended anti-infective prophylaxis treatment appears to be 
effective in reducing the risk of PCP and herpes infections (see section 4.4).  
 
EBV-associated lymphoproliferative disorders, in some cases fatal, have been reported. 
 
Blood and lymphatic system disorders:  Severe bleeding reactions have been reported.  
 
Immune system disorders:  Serious and sometimes fatal autoimmune phenomena including 
autoimmune haemolytic anaemia, autoimmune thrombocytopenia, aplastic anaemia, Guillain Barré 
syndrome and its chronic form, chronic inflammatory demyelinating polyradiculoneuropathy have 
been reported.  A positive Coombs test has also been observed.  Fatal Transfusion Associated Graft 
Versus Host Disease (TAGVHD) has also been reported. 
 
Metabolism and nutritional disorders:  Tumour lysis syndrome with fatal outcome has been reported.  
 
Nervous system disorders:  Intracranial haemorrhage has occurred with fatal outcome, in patients with 
thrombocytopenia. 
 
Cardiac disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction have 
been reported in patients previously treated with potentially cardiotoxic agents. 
 
4.9 Overdose 
 
Patients have received repeated unit doses of up to 240 mg of MabCampath.  The frequency of grade 3 
or 4 adverse events, such as fever, hypotension and anaemia, may be higher in these patients. There is 
no known specific antidote for MabCampath. Treatment consists of discontinuation of MabCampath 
and supportive therapy. 
 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

30 
 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC04. 
 
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 
21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal 
and malignant peripheral blood B and T cell lymphocytes. Alemtuzumab was generated by the 
insertion of six complementarity-determining regions from an IgG2a rat monoclonal antibody into a 
human IgG1 immunoglobulin molecule. 
 
Alemtuzumab causes the lysis of lymphocytes by binding to CD52, a highly expressed, non-
modulating antigen which is present on the surface of essentially all B and T cell lymphocytes as well 
as monocytes, thymocytes and macrophages. The antibody mediates the lysis of lymphocytes via 
complement fixation and antibody-dependent cell mediated cytotoxicity. The antigen has been found 
on a small percentage (< 5%) of granulocytes, but not on erythrocytes or platelets. Alemtuzumab does 
not appear to damage haematopoietic stem cells or progenitor cells. 
 
First line B-CLL patients  
 
The safety and efficacy of MabCampath  were evaluated in a Phase 3, open-label, randomized 
comparative trial of first line (previously untreated) Rai stage I-IV B-CLL patients requiring therapy 
(Study 4).  MabCampath was shown to be superior to chlorambucil as measured by the primary 
endpoint progression free survival (PFS) (see Figure 1). 
 

Figure 1:  Progression free survival in first line study (by treatment group) 
 

 
 
The secondary objectives included complete response (CR) and overall response (CR or partial 
response) rates using the 1996 NCIWG criteria, the duration of response, time to alternative treatment 
and safety of the two treatment arms. 
 Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

31 
 

Summary of first-line patient population and outcomes  
 
 Independent review of response rate and duration 
 MabCampath 

n=149 
Chlorambucil 
n=148 

P value 

Median Age (Years) 59 60 Not Applicable 
Rai Stage III/IV Disease 33.6% 33.1% Not Applicable 

Overall Response Rate 83.2% 55.4% <0.0001* 
Complete Response 24.2% 2.0% <0.0001* 
MRD negative**** 7.4% 0.0% 0.0008* 
Partial Response 59.1% 53.4% Not Applicable 
Duration of Response**, CR or 
PR (Months)  
K-M median (95% Confidence 
Interval) 

N=124 
16.2  

(11.5, 23.0) 

N=82 
12.7 

(10.2, 14.3)  

Not Applicable 

Time to Alternative Treatment 
(Months) 
K-M median (95% Confidence 
Interval) 

23.3  
(20.7, 31.0) 

14.7  
(12.6, 16.8) 

0.0001*** 

*Pearson chi-square test or Exact test 
** Duration of best response 
*** log-rank test stratified by Rai group (Stage I-II vs III-IV) 
**** by 4-colour flow  

 
Cytogenetic Analyses in first line B-CLL patients:  
 
The cytogenetic profile of B-CLL has been increasingly recognized as providing important prognostic 
information and may predict response to certain therapies. Of the first-line patients (n=282) in whom 
baseline cytogenetic (FISH) data were available in Study 4, chromosomal aberrations were detected in 
82%, while normal karyotype was detected in 18%.  Chromosomal aberrations were categorized 
according to Döhner’s hierarchical model.  In first line patients, treated with either MabCampath or 
chlorambucil, there were 21 patients with the 17p deletion, 54 patients with 11q deletion, 34 patients 
with trisomy 12, 51 patients with normal karyotype and 67 patients with sole 13q deletion.  
  
ORR was superior in patients with any 11q deletion (87% v 29%; p<0.0001) or sole deletion 13q (91% 
v 62%; p=0.0087) treated with MabCampath compared to chlorambucil. A trend toward improved 
ORR was observed in patients with 17p deletion treated with MabCampath (64% v 20%; p=0.0805). 
Complete remissions were also superior in patients with sole 13q deletion treated with MabCampath 
(27% v 0%; p=0.0009). Median PFS was superior in patients with sole 13q deletion treated with 
MabCampath (24.4 v 13.0 months; p=0.0170 stratified by Rai Stage).  A trend towards improved PFS 
was observed in patients with 17p deletion, trisomy 12 and normal karyotype, which did not reach 
significance due to small sample size. 
 
Assessment of CMV by PCR: 
  
In the randomized controlled trial in first line patients (Study 4), patients in the MabCampath arm were 
tested weekly for CMV using a PCR (polymerase chain reaction) assay from initiation through 
completion of therapy, and every 2 weeks for the first 2 months following therapy.  In this study, 
asymptomatic positive PCR only for CMV was reported in 77/147 (52.4%) of MabCampath-treated 
patients; symptomatic CMV infection was reported less commonly in 23/147 MabCampath treated 
patients (16%).  In the MabCampath arm 36/77 (46.8%) of patients with asymptomatic PCR positive 
CMV received antiviral therapy and 47/77 (61%) of these patients had MabCampath therapy 
interrupted.  The presence of asymptomatic positive PCR for CMV or symptomatic PCR positive 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

32 
 

CMV infection during treatment with MabCampath had no measurable impact on progression free 
survival (PFS). 
 
Previously treated B-CLL patients: 
 
Determination of the efficacy of MabCampath is based on overall response and survival rates. Data 
available from three uncontrolled B-CLL studies are summarised in the following table: 
 

Efficacy parameters Study 1 Study 2 Study 3 
Number of Patients 93 32 24 
Diagnostic Group B-CLL pts who had 

received an alkylating 
agent and had failed 

fludarabine 

B-CLL pts who had 
failed to respond or 
relapsed following 

treatment with 
conventional 
chemotherapy 

B-CLL (plus a PLL) 
pts who had failed to 
respond or relapsed 
following treatment 

with fludarabine 

Median Age (years) 66 57 62 
Disease Characteristics (%) 
     Rai Stage III/IV 
     B Symptoms 

 
76 
42 

 
72 
31 

 
71 
21 

Prior Therapies (%): 
     Alkylating Agents 
     Fludarabine 

 
100 
100 

 
100 
34 

 
92 

100 
Number of Prior Regimens (range) 3 (2-7) 3 (1-10)  3 (1-8) 
Initial Dosing Regimen Gradual escalation 

from 3 to 10 to 30 mg 
Gradual escalation 
from 10 to 30 mg 

Gradual escalation 
from 10 to 30 mg 

Final Dosing Regimen 30 mg iv 3 x weekly 30 mg iv 3 x weekly 30 mg iv 3 x weekly 
Overall Response Rate (%) 
(95% Confidence Interval) 
     Complete Response 
     Partial Response 

33  
 (23-43) 

2 
31 

21  
(8-33) 

0 
21 

29  
(11-47) 

0 
29 

Median Duration of Response (months) 
(95% Confidence Interval) 

7  
(5-8) 

7 
 (5-23) 

11  
(6-19) 

Median time to Response (months) 
(95% Confidence Interval) 

2  
(1-2) 

4  
(1-5) 

4 
 (2-4) 

Progression-Free Survival (months)  
(95% Confidence Interval) 

4  
(3-5) 

5  
(3-7) 

7  
(3-9) 

Survival (months): 
(95% Confidence Interval) 
     All patients 
     Responders 

 
 

16 (12-22) 
33 (26-NR) 

 
 

26 (12-44) 
44 (28-NR) 

 
 

28 (7-33) 
36 (19-NR) 

NR = not reached 
 
5.2 Pharmacokinetic properties 
 
Pharmacokinetics were characterised in MabCampath-naive patients with B-cell chronic lymphocytic 
leukaemia (B-CLL) who had failed previous therapy with purine analogues. MabCampath was 
administered as a 2 hour intravenous infusion, at the recommended dosing schedule, starting at 3 mg 
and increasing to 30 mg, 3 times weekly, for up to 12 weeks. MabCampath pharmacokinetics followed 
a 2-compartment model and displayed non-linear elimination kinetics.  After the last 30 mg dose, the 
median volume of distribution at steady-state was 0.15 l/kg (range: 0.1-0.4 l/kg), indicating that 
distribution was primarily to the extracellular fluid and plasma compartments. Systemic clearance 
decreased with repeated administration due to decreased receptor-mediated clearance (i.e. loss of 
CD52 receptors in the periphery). With repeated administration and consequent plasma concentration 
accumulation, the rate of elimination approached zero-order kinetics.  As such, half-life was 8 hours 
(range: 2-32 hours) after the first 30 mg dose and was 6 days (range: 1-14 days) after the last 30 mg 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

33 
 

dose. Steady-state concentrations were reached after about 6 weeks of dosing. No apparent difference 
in pharmacokinetics between males and females was observed nor was any apparent age effect 
observed.   
 
5.3 Preclinical safety data 
 
Preclinical evaluation of alemtuzumab in animals has been limited to the cynomolgus monkey because 
of the lack of expression of the CD52 antigen on non-primate species. 
 
Lymphocytopenia was the most common treatment-related effect in this species. A slight cumulative 
effect on the degree of lymphocyte depletion was seen in repeated dose studies compared to single 
dose studies. Lymphocyte depletion was rapidly reversible after cessation of dosing. Reversible 
neutropenia was seen following daily intravenous or subcutaneous dosing for 30 days, but not 
following single doses or daily dosing for 14 days. Histopathology results from bone marrow samples 
revealed no remarkable changes attributable to treatment. Single intravenous doses of 10 and 30 mg/kg 
produced moderate to severe dose related hypotension accompanied by a slight tachycardia. 
 
MabCampath Fab binding was observed in lymphoid tissues and the mononuclear phagocyte system.  
Significant Fab binding was also observed in the male reproductive tract (epididymis, sperm, seminal 
vesicle) and the skin. 
 
No other findings, in the above toxicity studies, provide information of significant relevance to clinical 
use. 
 
No short or long term animal studies have been conducted with MabCampath to assess carcinogenic 
and mutagenic potential.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium edetate  
Polysorbate 80 
Potassium chloride 
Potassium dihydrogen phosphate 
Sodium chloride 
Dibasic sodium phosphate 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.  
 
There are no known incompatibilities with other medicinal products. However, other medicinal 
products should not be added to the MabCampath infusion or simultaneously infused through the same 
intravenous line. 
 
6.3 Shelf life 
 
Unopen vial: 3 years. 
 
Reconstituted solution: MabCampath contains no antimicrobial preservative. MabCampath should be 
used within 8 hours after dilution. Solutions may be stored at 15C-30C or refrigerated. This can only 
be accepted if preparation of the solution takes place under strictly aseptic conditions and the solution 
is protected from light. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

34 
 

 
6.4 Special precautions for storage 
 
Store in a refrigerator (2C-8C).  
Do not freeze. 
Store in the original package in order to protect from light. 
 
For storage conditions of the reconstituted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Clear type I glass vial, closed with a rubber stopper, containing 1 ml of concentrate. 
 
Pack size: carton of 3 vials. 
 
6.6 Special precautions for disposal and other handling 
 
The vial contents should be inspected for particulate matter and discolouration prior to administration. 
If particulate matter is present or the concentrate is coloured, then the vial should not be used. 
 
MabCampath contains no antimicrobial preservatives, therefore, it is recommended that MabCampath 
should be prepared for intravenous infusion using aseptic techniques and that the diluted solution for 
infusion should be administered within 8 hours after preparation and protected from light. The 
required amount of the vial contents should be added to 100 ml of sodium chloride 9 mg/ml (0.9%) 
solution for infusion or glucose (5%) solution for infusion. The bag should be inverted gently to mix 
the solution. Care should be taken to ensure the sterility of the prepared solution particularly as it 
contains no antimicrobial preservatives. 
 
Other medicinal products should not be added to the MabCampath infusion solution or simultaneously 
infused through the same intravenous line (see section 4.5). 
 
Caution should be exercised in the handling and preparation of the MabCampath solution. The use of 
latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or 
other accidental spillage. Women who are pregnant or trying to become pregnant should not handle 
MabCampath.   
 
Procedures for proper handling and disposal should be observed. Any spillage or waste material 
should be disposed of by incineration.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe BV 
Gooimeer 10 
1411 DD Naarden 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/01/193/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 06/07/2001 
Date of latest renewal: 10/07/2011 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

35 
 

 
 
10. DATE OF REVISION OF THE TEXT 
 

 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu. 
 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

36 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

37 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Boehringer Ingelheim Pharma GmbH & Co. KG  
Birkendorfer Strasse 65 
D-88397 Biberach an der Riss 
Deutschland 
 
Genzyme Flanders bvba 
Cipalstraat 8 
2440 Geel 
Belgium 
 
Name and address of the manufacturer responsible for batch release 
 
Genzyme Ltd. 
37 Hollands Road 
Haverhill, Suffolk CB9 8PU  
United Kingdom 
 
Genzyme Ireland Limited. 
IDA Industrial Park 
Old Kilmeaden Road 
Waterford 
Ireland  
 
Bayer Schering Pharma AG 
Müllerstrasse 178 
D-13342 Berlin 
Deutschland 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
 CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to restricted medical prescription (See Annex 1: Summary of Product 
Characteristics, section 4.2). 
 
 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
The MAH shall agree the details of an educational brochure with the National Competent 
Authorities.  
 
The MAH shall ensure that all doctors who prescribe MabCampath are provided with a 
healthcare professional information pack containing the following: 

 Educational brochure 
 Summary of Product Characteristics (SPC) and Package Leaflet and Labelling 

 
Me

dic
ina

l p
rod

uc
t n

o l
on

ge
r a

uth
ori

se
d



 

38 
 

Key elements to be included in the educational brochure 
 

 The risk of opportunistic infections, in particular CMV viraemia 
 Recommendation to avoid vaccination with live vaccines for at least 12 months following 

MabCampath therapy 
 The risk of infusion reactions 

o Need for premedication 
o That treatment for hypersensitivity reactions, including measures for resuscitation 

should be available during administration 
o That the risk of infusion reactions is highest in first week of therapy 
o That if the reaction is moderate or severe dosing should continue at the same level (ie 

no dose escalation) until each dose is well tolerated 
o That if therapy is withheld for more than 7 days then MabCampath should be 

reinstituted with gradual dose escalation 
 
 OTHER CONDITIONS  
 
The MAH will continue to submit yearly PSURs, unless otherwise specified by the CHMP. 
 
Risk Management Plan 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the Pharmacovigilance Plan, as agreed in version 3.3 of the Risk Management Plan (RMP) presented 
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP 
agreed by the CHMP.  
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 
updated RMP should be submitted at the same time as the next Periodic Safety Update Report 
(PSUR). 
 
In addition, an updated RMP should be submitted: 

 When new information is received that may impact on the current Safety Specification, 
Pharmacovigilance Plan or risk minimisation activities 

 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 
reached 

 At the request of the EMA  
 

 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

39 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

40 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

41 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
MabCampath 10 mg/ml concentrate for solution for infusion 
Alemtuzumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One ml contains 10 mg of alemtuzumab. 
Each ampoule contains 30 mg of alemtuzumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: 
Disodium edetate, polysorbate 80, potassium chloride, potassium dihydrogen phosphate, sodium 
chloride, dibasic sodium phosphate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
3 x 3 ml ampoules 
30 mg/3 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Read the leaflet for the shelf life of the reconstituted product. 
 Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

42 
 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator (2°C-8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any spillage or waste material should be disposed of by incineration. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Marketing Authorisation Holder: 
Genzyme Europe BV, Gooimeer 10, 1411 DD Naarden, Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/01/193/001 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

43 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
AMPOULE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
MabCampath 10 mg/ml concentrate for solution for infusion 
Alemtuzumab 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 mg/3 ml 
 
 
6. OTHER 
 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

44 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
MabCampath 30 mg/ml concentrate for solution for infusion 
Alemtuzumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One ml contains 30 mg of alemtuzumab. 
Each vial contains 30 mg of alemtuzumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: 
Disodium edetate, polysorbate 80, potassium chloride, potassium dihydrogen phosphate, sodium 
chloride, dibasic sodium phosphate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
3 x 1 ml vials 
30 mg/ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
Read the leaflet for the shelf life of the reconstituted product. 
 Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

45 
 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator (2°C-8°C). 
Do not freeze. 
Store in the original package in order to protect from light,. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any spillage or waste material should be disposed of by incineration. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Marketing Authorisation Holder: 
Genzyme Europe BV, Gooimeer 10, 1411 DD Naarden, Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER (S) 
 
EU/1/01/193/002 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

46 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
MabCampath 30 mg/ml concentrate for solution for infusion 
Alemtuzumab 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 mg/ml 
 
 
6. OTHER 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

47 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

48 
 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

MabCampath 10 mg/ml concentrate for solution for infusion 
Alemtuzumab 

 
Read all of this leaflet carefully before you start using this medicine. 
 
 Keep this leaflet. You may need to read it again. 
 If you have any further questions, ask your doctor or pharmacist. 
 If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet: 
 
1. What MabCampath is and what it is used for 
2. Before you use MabCampath 
3. How to use MabCampath 
4. Possible side effects 
5. How to store MabCampath 
6. Further information 
 
 
1. WHAT MABCAMPATH IS AND WHAT IT IS USED FOR 
 
MabCampath is used to treat patients with chronic lymphocytic leukaemia (CLL), a cancer of the 
lymphocytes (a type of white blood cell). It is used in patients for whom treatment combinations 
including fludarabine (another medicine used in leukaemia) are not appropriate.  
 
The active substance in MabCampath, alemtuzumab, is a monoclonal antibody. A monoclonal 
antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific 
structure (called an antigen) that is found in certain cells in the body. In CLL, too many lymphocytes 
are produced. Alemtuzumab has been designed to bind to a glycoprotein (a protein that is coated with 
sugar molecules) that is found on the surface of lymphocytes. As a result of this binding, the 
lymphocytes die, and this helps to control the CLL. 
 
 
2. BEFORE YOU USE MABCAMPATH 
 
Do not use MabCampath if you: 
 
 are allergic to alemtuzumab or to proteins of a similar origin or to any of the other ingredients of 

MabCampath (see section 6 “Further Information”). Your doctor will inform you accordingly 
 have an infection 
 have HIV 
 have an active second malignancy 
 are pregnant (see also “Pregnancy”). 
 
Take special care with MabCampath: 
 
When you first receive MabCampath, you may experience side effects soon after the first infusions 
(see section 4 “Possible side effects”). These effects will gradually reduce as treatment is continued.  
 Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

49 
 

You may also be given 
 
 steroids, antihistamines or analgesics (treatment for fever) to help reduce some of the side 

effects.  
 
The dosage of MabCampath will not be increased until the effects are reduced. 
 
MabCampath treatment may reduce your natural resistance to infections 
 
 antibiotics and antivirals may be given to provide you with extra protection.  
 
You will be examined for symptoms of a certain type of viral infection called CMV (cytomegalovirus) 
during your MabCampath therapy and for at least 2 months afterwards.   
 
Your doctor will monitor you carefully if you 
 
 have heart disease or chest pains and/or you are receiving treatment to reduce high blood 

pressure, as MabCampath may make these conditions worse.  
Patients with these conditions may be at higher risk of a heart attack. 

 
 have been treated in the past with chemotherapies or general medications that have a high risk 

of causing heart damage, your doctor may wish to monitor your cardiac function (ECG, heart 
rate, body weight) while receiving MabCampath. 

 
 have other side effects, most often blood disorders from taking MabCampath.  

Your doctor will be monitoring the effects of treatment and your progress carefully by 
examining you and by taking blood samples for analysis on a regular basis.  

 
 are over 65 years of age as you may be more intolerant to the medicine than other patients. 
 
You may experience an allergic or hypersensitivity reaction to MabCampath solution, especially 
against the protein contained in it, while the infusion is given to you.  Your doctor will treat you for 
this, if this happens. 
 
Because of the potential for a fatal reaction to transfusion of any blood products following treatment 
with MabCampath, it is recommended that you speak to your doctor regarding the irradiation of 
blood products prior to receiving the transfusion. You should inform your doctor if you experience 
any unusual symptoms after a transfusion. 
 
MabCampath is not recommended in children below 17 years of age or in patients who have kidney or 
liver disorders. 
 
Taking other medicines 
 
You should inform your doctor if you are taking or have recently taken any other medicines, even 
those not prescribed. 
 
In particular, you should not be given MabCampath within 3 weeks of taking any other anti-cancer 
agents.  
 
Also, you should not be vaccinated with live viral vaccines during treatment and for at least 12 months 
after you have finished your treatment. Speak to your doctor before receiving any vaccinations. 
 
Pregnancy  
 
MabCampath must not be administered to patients who are pregnant, therefore if you: 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

50 
 

 are pregnant or you think you may be pregnant, you should tell your doctor immediately. 
 are a woman of childbearing potential or a fertile man, then you should use effective 

contraceptive methods before you start treatment, during treatment and for 6 months after 
treatment. 

 
Breast-feeding 
 
You should stop breast-feeding when you start your treatment and you should not begin breast-feeding 
again until at least 4 weeks after you have finished your treatment and you have consulted your doctor 
on the matter.  
 
Driving or using machines 
 
No studies of the effects of MabCampath on the ability to drive and use machines have been 
performed. However you should be cautious as confusion and sleepiness have been seen. You should 
ask your doctor for advice. 
 
 
3. HOW TO USE MABCAMPATH 
 
MabCampath is administered into one of your veins via a drip (see also ‘information intended for 
medical or healthcare professionals’). 
 
Each time you are given MabCampath, it will take about 2 hours for all the solution to enter your 
blood. 
 
MabCampath treatment may continue for up to 12 weeks depending on your progress. 
 
During the first week, your doctor will increase the dose of MabCampath slowly to reduce the 
possibility of you having side effects and to allow your body to tolerate MabCampath better. 
 
If you experience early side effects the initial smaller doses may be repeated until the effects go away 
or reduce. The doctor will carefully monitor you and decide what are the appropriate amounts of 
MabCampath to give you during your whole treatment period. 
 
If more MabCampath is given than recommended 
 
Your doctor will treat you, as appropriate, if you have any side effects. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, MabCampath can cause side effects, although not everybody gets them.  
 
Your doctor may give you other medicines or change your dose to help reduce any side effects 
(see section 2 “Take Special care”). 
 
Serious side effects, including difficulty in breathing, inflammation of the lungs, extreme shortness of 
breath, fainting, heart attack, low red blood cell and low blood platelet levels, infections, bleeding in 
the brain (intracranial haemorrhage) have occurred with fatal outcome. Diseases related to an 
overactive immune system where your immune system attacks your own body can lead to low red 
blood cells, low blood platelets and/or low white blood cells, and nerve disorders, and these can also 
be fatal. Tell your doctor immediately if you experience any of these side effects. 
 
In addition, testing indicating the presence of antibodies that may destroy red blood cells (Coombs 
test) has been reported. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

51 
 

Very common side effects (seen in at least 1 in every 10 patients treated in clinical trials):  
 
Usually one or more of these effects happen during the first week after the start of treatment:  
 
 fever, shivering/chills, sweating, nausea (feeling sick), vomiting, low blood pressure, low 

white/red blood cell levels, infections including pneumonia and blood poisoning, irritation 
and/or blistering of the mouth region, low blood platelet levels, tiredness, rash, itching, red 
raised lesions on the skin, shortness of breath, headache, diarrhoea and loss of appetite.  

 
They are usually only mild or moderate problems and they gradually diminish during the course of 
treatment. 

 
Common side effects (affects 1 to 10 patients in every 100 patients treated in clinical trials): 
 
 high blood pressure, fast or slow heart rate, feeling your heart racing, blood vessel spasm  
 becoming red in the face, bruising of the skin  
 taste changes 
 decreased sense of touch 
 dizziness, sensation of spinning, fainting, shaking or trembling movements, feeling restless  
 eye inflammation (e.g. conjunctivitis) 
 pins and needles or burning sensation of the skin 
 abnormal liver function, constipation, indigestion, passing abdominal gas 
 inflammation, irritation and/or tightness of the lungs, throat and/or sinuses, too little oxygen 

reaching the body organs, coughing, coughing up of blood 
 abdominal bleeding (e.g. in the stomach and intestine) 
 injection site reactions including redness, swelling, pain, bruising, inflammation 
 generally feeling unwell, weakness, pain in various parts of the body (muscle, back, chest, 

bones, joints, stomach and intestine) 
 weight loss, dehydration, thirst, swelling of the lower legs, temperature change sensation, low 

calcium or sodium blood levels 
 flu-like symptoms 
 abscess, skin redness or allergic skin reaction, blistering of the skin 
 confusion, anxiety, depression, sleeplessness 
 
Uncommon side effects (affects 1 to 10 patients in every 1,000 patients treated in clinical trials):  
 
 bone marrow disorders 
 heart disorders (heart stopping, heart attack, heart congestion, irregular heart rate) 
 blood disorders (abnormal clotting, decreased protein, low potassium levels) 
 high blood sugar, worsening diabetes 
 bleeding and inflammation of the gums, blisters on the tongue, nosebleeds 
 fluid in the lungs, difficulty breathing, harsh sound when breathing, runny nose, abnormal 

findings in the lungs, lymph gland disorders 
 nervousness, abnormal thinking 
 swelling around the eye 
 ringing sound in the ears, deafness 
 hiccups, burping 
 hoarseness 
 abnormal kidney function 
 paralysis of the small bowel 
 impotence 
 unsteadiness, increased muscle tone 
 unusual increased or altered sensitivity to touch 
 abnormal sensation/feeling or movement  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

52 
 

 pain when urinating, decreases in urine flow, increased frequency in urination, blood in urine, 
incontinence 

 tumour lysis syndrome (a metabolic disorder, which may begin with pains in the side and blood 
in the urine)  

 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or your pharmacist. 
 
 
5. HOW TO STORE MABCAMPATH 
 
Keep out of the reach and sight of children.  
 
Do not use MabCampath after the expiry date (EXP) which is stated on the outer carton and the 
ampoule label. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2C-8C).  
 
Do not freeze. 
 
Store in the original packaging in order to protect from light. 
 
MabCampath should be used within 8 hours after dilution. During that time the solution may be stored 
at 15°C-30°C or refrigerated. 
 
Do not use MabCampath if you notice any signs of particulate matter or discolouration prior to 
administration.   
 
Medicines should not be disposed of via wastewater or household waste. Your healthcare professional 
will dispose of medicines no longer required. These measures will help protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What MabCampath contains 
 
The active substance is alemtuzumab. 
One ml contains 10 mg of alemtuzumab. Each ampoule contains 30 mg of alemtuzumab. 
 
The other ingredients are disodium edetate, polysorbate 80, potassium chloride, potassium dihydrogen 
phosphate, sodium chloride, dibasic sodium phosphate and water for injections.  
 
What MabCampath looks like and contents of the pack 
 
MabCampath is a concentrate for solution for infusion that comes in a glass ampoule.  
 
Each pack of MabCampath contains 3 ampoules. 
 
Marketing Authorisation Holder  
 
Genzyme Europe BV, Gooimeer 10, 1411 DD Naarden, Netherlands 
 
Manufacturer  
 
Genzyme Ltd., 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom 
 
Genzyme Ireland Limited., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

53 
 

 
Bayer Schering Pharma AG, Müllerstrasse 178, D-13342 Berlin, Germany. 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien/ 
Luxemburg/ Luxembourg 
Genzyme Belgium N.V., 
Tél/Tel: + 32 2 714 17 11  
 

Italia/Malta 
Genzyme Srl (Italia/Italja),  
Tel: +39 059 349 811 
 

България 
Джензайм ЕООД 
Тел. +359 2 971 1001 
 

Magyarország 
Genzyme Europe B.V. Képviselet 
Tel: +36 1 310 7440 
 

Česká Republika/Slovenská Republika/ 
Slovenija 
Genzyme Czech s.r.o. 
Tel: +420 221 722 511 
 

Nederland 
Genzyme Europe B.V.,  
Tel: +31 35 699 1200 
 

Danmark/Norge/Sverige/Suomi/Finland/ 
Ísland 
Genzyme A/S, (Danmark/Tanska/Danmörk), 
Tlf/Puh./Sími: + 45 32712600 
 

Österreich 
Genzyme Austria GmbH,  
Tel: + 43 1 774 65 38 
 

Deutschland 
Genzyme GmbH,  
Tel: +49 610236740 
 

Polska/Eesti/Latvija/Lietuva 
Genzyme Polska Sp. z o.o.  
(Poola/Polija/Lenkija),  
Tel: + 48 22 246 0900 
 

Ελλάδα/Κύπρος 
Genzyme Hellas Ltd. (Ελλάδα) 
Τηλ: +30 210 99 49 270 
 

Portugal 
Genzyme Portugal S.A.  
Tel: +351 21 422 0100 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

România 
Genzyme Biopharma SRL 
Tel: +40 212 43 42 28 
 

France 
Genzyme S.A.S,  
Tél: + 33 (0) 825 825 863 
 

United Kingdom/Ireland 
Genzyme Therapeutics Ltd. (United 
Kingdom),  
Tel: +44 1865 405200 
 

 
This leaflet was last approved in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

54 
 

The following information is intended for medical or healthcare professionals only: 
 
During the first week, 3 mg of MabCampath is given on Day 1, then 10 mg on Day 2 and then 30 mg 
on Day 3, depending on tolerability. MabCampath will be given at 30 mg three times per calendar 
week on alternate days, for up to 12 weeks.   
 
The ampoule contents should be inspected for particulate matter and discolouration prior to 
administration. If particulate matter is present or the solution is coloured, then the ampoule should not 
be used. 
 
MabCampath contains no antimicrobial preservatives, therefore, it is recommended that MabCampath 
should be prepared for intravenous infusion using aseptic techniques and that the diluted solution for 
infusion should be administered within 8 hours after preparation and protected from light. The 
required amount of the ampoule contents should be added, via a sterile, low-protein binding, non-fibre 
5 μm filter, to 100 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose (5%) 
solution for infusion. The bag should be inverted gently to mix the solution. Care should be taken to 
ensure the sterility of the prepared solution particularly as it contains no antimicrobial preservatives. 
 
Other medicinal products should not be added to the MabCampath infusion solution or simultaneously 
infused though the same intravenous line. 
 
Caution should be exercised in the handling and preparation of the MabCampath solution. The use of 
latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the ampoule 
or other accidental spillage. Women who are pregnant or trying to become pregnant should not handle 
MabCampath. 
 
Procedures for proper handling and disposal should be observed. Any spillage or waste material 
should be disposed of by incineration.  
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

55 
 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

MabCampath 30 mg/ml concentrate for solution for infusion 
Alemtuzumab 

 
Read all of this leaflet carefully before you start using this medicine 
 
 Keep this leaflet. You may need to read it again. 
 If you have any further questions, ask your doctor or pharmacist. 
 If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
 
1. What MabCampath is and what it is used for 
2. Before you use MabCampath 
3. How to use MabCampath  
4. Possible side effects 
5. How to store MabCampath 
6. Further information 
 
 
1. WHAT MABCAMPATH IS AND WHAT IT IS USED FOR 
 
MabCampath is used to treat patients with chronic lymphocytic leukaemia (CLL), a cancer of the 
lymphocytes (a type of white blood cell). It is used in patients for whom treatment combinations 
including fludarabine (another medicine used in leukaemia) are not appropriate.  
 
The active substance in MabCampath, alemtuzumab, is a monoclonal antibody. A monoclonal 
antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific 
structure (called an antigen) that is found in certain cells in the body. In CLL, too many lymphocytes 
are produced. Alemtuzumab has been designed to bind to a glycoprotein (a protein that is coated with 
sugar molecules) that is found on the surface of lymphocytes. As a result of this binding, the 
lymphocytes die, and this helps to control the CLL. 
 
 
2. BEFORE YOU USE MABCAMPATH 
 
Do not use MabCampath if you: 
 
 are allergic to alemtuzumab or to proteins of a similar origin or to any of the other ingredients of 

MabCampath (see section 6 “Further Information”). Your doctor will inform you accordingly 
 have an infection 
 have HIV 
 have an active second malignancy 
 are pregnant (see also “Pregnancy”). 
 
Take special care with MabCampath: 
 
When you first receive MabCampath, you may experience side effects soon after the first infusions 
(see section 4 “Possible side effects”). These effects will gradually reduce as treatment is continued.  
 
You may also be given 
 
 steroids, antihistamines or analgesics (treatment for fever) to help reduce some of the side 

effects.  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

56 
 

 
The dosage of MabCampath will not be increased until the effects are reduced. 
 
MabCampath treatment may reduce your natural resistance to infections 
 
 antibiotics and antivirals may be given to provide you with extra protection.  
 
You will be examined for symptoms of a certain type of viral infection called CMV (cytomegalovirus) 
during your MabCampath therapy and for at least 2 months afterwards.   
 
Your doctor will monitor you carefully if you 
 
 have heart disease or chest pains and/or you are receiving treatment to reduce high blood 

pressure, as MabCampath may make these conditions worse.  
Patients with these conditions may be at higher risk of a heart attack. 

 
 have been treated in the past with chemotherapies or general medications that have a high risk 

of causing heart damage, your doctor may wish to monitor your cardiac function (ECG, heart 
rate, body weight) while receiving MabCampath. 

 
 have other side effects, most often blood disorders from taking MabCampath.  

Your doctor will be monitoring the effects of treatment and your progress carefully by 
examining you and by taking blood samples for analysis on a regular basis.  

 
 are over 65 years of age as you may be more intolerant to the medicine than other patients. 
 
You may experience an allergic or hypersensitivity reaction to MabCampath solution, especially 
against the protein contained in it, while the infusion is given to you.  Your doctor will treat you for 
this, if this happens. 
 
Because of the potential for a fatal reaction to transfusion of any blood products following treatment 
with MabCampath, it is recommended that you speak to your doctor regarding the irradiation of 
blood products prior to receiving the transfusion. You should inform your doctor if you experience 
any unusual symptoms after a transfusion. 
 
MabCampath is not recommended in children below 17 years of age or in patients who have kidney or 
liver disorders. 
 
Taking other medicines 
 
You should inform your doctor if you are taking or have recently taken any other medicines, even 
those not prescribed. 
 
In particular, you should not be given MabCampath within 3 weeks of taking any other anti-cancer 
agents.  
 
Also, you should not be vaccinated with live viral vaccines during treatment and for at least 12 months 
after you have finished your treatment. Speak to your doctor before receiving any vaccinations. 
 
Pregnancy  
 
MabCampath must not be administered to patients who are pregnant, therefore if you: 
 
 are pregnant or you think you may be pregnant, you should tell your doctor immediately. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

57 
 

 are a woman of childbearing potential or a fertile man, then you should use effective 
contraceptive methods before you start treatment, during treatment and for 6 months after 
treatment. 

 
Breast-feeding 
 
You should stop breast-feeding when you start your treatment and you should not begin breast-feeding 
again until at least 4 weeks after you have finished your treatment and you have consulted your doctor 
on the matter.  
 
Driving or using machines 
 
No studies of the effects of MabCampath on the ability to drive and use machines have been 
performed. However you should be cautious as confusion and sleepiness have been seen. You should 
ask your doctor for advice. 
 
 
3. HOW TO USE MABCAMPATH  
 
MabCampath is administered into one of your veins via a drip (see also ‘information intended for 
medical or healthcare professionals’). 
 
Each time you are given MabCampath, it will take about 2 hours for all the solution to enter your 
blood. 
 
MabCampath treatment may continue for up to 12 weeks depending on your progress. 
 
During the first week, your doctor will increase the dose of MabCampath slowly to reduce the 
possibility of you having side effects and to allow your body to tolerate MabCampath better. 
 
If you experience early side effects the initial smaller doses may be repeated until the effects go away 
or reduce. The doctor will carefully monitor you and decide what are the appropriate amounts of 
MabCampath to give you during your whole treatment period. 
 
If more MabCampath is given than recommended 
 
Your doctor will treat you, as appropriate, if you have any side effects. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, MabCampath can cause side effects, although not everybody gets them.  
 
Your doctor may give you other medicines or change your dose to help reduce any side effects 
(see section 2 “Take Special care”). 
 
Serious side effects, including difficulty in breathing, inflammation of the lungs, extreme shortness of 
breath, fainting, heart attack, low red blood cell and low blood platelet levels, infections, bleeding in 
the brain (intracranial haemorrhage) have occurred with fatal outcome. Diseases related to an 
overactive immune system where your immune system attacks your own body can lead to low red 
blood cells, low blood platelets and/or low white blood cells, and nerve disorders, and these can also 
be fatal. Tell your doctor immediately if you experience any of these side effects.   
 
In addition, testing indicating the presence of antibodies that may destroy red blood cells (Coombs 
test) has been reported. 
 
Very common side effects (seen in at least 1 in every 10 patients treated in clinical trials):  

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

58 
 

 
Usually one or more of these effects happen during the first week after the start of treatment:  
 
 fever, shivering/chills, sweating, nausea (feeling sick), vomiting, low blood pressure, low 

white/red blood cell levels, infections including pneumonia and blood poisoning, irritation 
and/or blistering of the mouth region, low blood platelet levels, tiredness, rash, itching, red 
raised lesions on the skin, shortness of breath, headache, diarrhoea and loss of appetite.  

  
 They are usually only mild or moderate problems and they gradually diminish during the course of 

treatment. 
 

Common side effects (affects 1 to 10 patients in every 100 patients treated in clinical trials): 
 
 high blood pressure, fast or slow heart rate, feeling your heart racing, blood vessel spasm  
 becoming red in the face, bruising of the skin  
 taste changes 
 decreased sense of touch 
 dizziness, sensation of spinning, fainting, shaking or trembling movements, feeling restless  
 eye inflammation (e.g. conjunctivitis) 
 pins and needles or burning sensation of the skin 
 abnormal liver function, constipation, indigestion, passing abdominal gas 
 inflammation, irritation and/or tightness of the lungs, throat and/or sinuses, too little oxygen 

reaching the body organs, coughing, coughing up of blood 
 abdominal bleeding (e.g. in the stomach and intestine) 
 injection site reactions including redness, swelling, pain, bruising, inflammation 
 generally feeling unwell, weakness, pain in various parts of the body (muscle, back, chest, 

bones, joints, stomach and intestine) 
 weight loss, dehydration, thirst, swelling of the lower legs, temperature change sensation, low 

calcium or sodium blood levels 
 flu-like symptoms 
 abscess, skin redness or allergic skin reaction, blistering of the skin 
 confusion, anxiety, depression, sleeplessness 
 
Uncommon side effects (affects 1 to 10 in every patients in 1,000 patients treated in clinical trials):  
 
 bone marrow disorders 
 heart disorders (heart stopping, heart attack, heart congestion, irregular heart rate) 
 blood disorders (abnormal clotting, decreased protein, low potassium levels) 
 high blood sugar, worsening diabetes 
 bleeding and inflammation of the gums, blisters on the tongue, nosebleeds 
 fluid in the lungs, difficulty breathing, harsh sound when breathing, runny nose, abnormal 

findings in the lungs, lymph gland disorders 
 nervousness, abnormal thinking 
 swelling around the eye 
 ringing sound in the ears, deafness 
 hiccups, burping 
 hoarseness 
 abnormal kidney function 
 paralysis of the small bowel 
 impotence 
 unsteadiness, increased muscle tone 
 unusual increased or altered sensitivity to touch’ 
 abnormal sensation/feeling or movement 
 pain when urinating, decreases in urine flow, increased frequency in urination, blood in urine, 

incontinence 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

59 
 

 tumour lysis syndrome (a metabolic disorder, which may begin with pains in the side and blood 
in the urine)  

 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or your pharmacist. 
 
 
5. HOW TO STORE MABCAMPATH 
 
Keep out of the reach and sight of children.  
 
Do not use MabCampath after the expiry date (EXP) which is stated on the outer carton and the vial 
label. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2C-8C).  
 
Do not freeze. 
 
Store in the original packaging in order to protect from light. 
 
MabCampath should be used within 8 hours after dilution. During that time the solution may be stored 
at 15°C-30°C or refrigerated. 
 
Do not use MabCampath if you notice any signs of particulate matter or discolouration prior to 
administration.   
 
Medicines should not be disposed of via wastewater or household waste. Your healthcare professional 
will dispose of medicines no longer required. These measures will help protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What MabCampath contains 
 
The active substance is alemtuzumab. 
One ml contains 30 mg of alemtuzumab. Each vial contains 30 mg of alemtuzumab. 
 
The other ingredients are disodium edetate, polysorbate 80, potassium chloride, potassium dihydrogen 
phosphate, sodium chloride, dibasic sodium phosphate and water for injections.  
 
What MabCampath looks like and contents of the pack 
 
MabCampath is a concentrate for solution for infusion that comes in a glass vial.  
 
Each pack of MabCampath contains 3 vials. 
 
Marketing Authorisation Holder  
 
Genzyme Europe BV, Gooimeer 10, 1411 DD Naarden, Netherlands 
 
Manufacturer  
 
Genzyme Ltd., 37 Hollands Road, Haverhill, Suffolk CB9 8PU, United Kingdom 
 
Genzyme Ireland Limited., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland  
 
Bayer Schering Pharma AG, Müllerstrasse 178, D-13342 Berlin, Germany. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

60 
 

 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien/ 
Luxemburg/ Luxembourg 
Genzyme Belgium N.V., 
Tél/Tel: + 32 2 714 17 11  
 

Italia/Malta 
Genzyme Srl (Italia/Italja),  
Tel: +39 059 349 811 
 

България 
Джензайм ЕООД 
Тел. +359 2 971 1001 
 

Magyarország 
Genzyme Europe B.V. Képviselet 
Tel: +36 1 310 7440 
 

Česká Republika/Slovenská Republika/ 
Slovenija 
Genzyme Czech s.r.o. 
Tel: +420 221 722 511 
 

Nederland 
Genzyme Europe B.V.,  
Tel: +31 35 699 1200 
 

Danmark/Norge/Sverige/Suomi/Finland/ 
Ísland 
Genzyme A/S, (Danmark/Tanska/Danmörk), 
Tlf/Puh./Sími: + 45 32712600 
 

Österreich 
Genzyme Austria GmbH,  
Tel: + 43 1 774 65 38 
 

Deutschland 
Genzyme GmbH,  
Tel: +49 610236740 
 

Polska/Eesti/Latvija/Lietuva 
Genzyme Polska Sp. z o.o.  
(Poola/Polija/Lenkija),  
Tel: + 48 22 246 0900 
 

Ελλάδα/Κύπρος 
Genzyme Hellas Ltd. (Ελλάδα) 
Τηλ: +30 210 99 49 270 
 

Portugal 
Genzyme Portugal S.A.  
Tel: +351 21 422 0100 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

România 
Genzyme Biopharma SRL 
Tel: +40 212 43 42 28 
 

France 
Genzyme S.A.S,  
Tél: + 33 (0) 825 825 863 
 

United Kingdom/Ireland 
Genzyme Therapeutics Ltd. (United 
Kingdom),  
Tel: +44 1865 405200 
 

 
This leaflet was last approved in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
The following information is intended for medical or healthcare professionals only: 
 
During the first week, 3 mg of MabCampath is given on Day 1, then 10 mg on Day 2 and then 30 mg 
on Day 3, depending on tolerability. MabCampath will be given at 30 mg three times per calendar 
week on alternate days, for up to 12 weeks. 
 
The vial contents should be inspected for particulate matter and discolouration prior to administration. 
If particulate matter is present or the solution is coloured, then the vial should not be used. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 

61 
 

MabCampath contains no antimicrobial preservatives, therefore, it is recommended that MabCampath 
should be prepared for intravenous infusion using aseptic techniques and that the diluted solution for 
infusion should be administered within 8 hours after preparation and protected from light. The 
required amount of the vial contents should be added to 100 ml of sodium chloride 9 mg/ml (0.9%) 
solution for infusion or glucose (5%) solution for infusion. The bag should be inverted gently to mix 
the solution. Care should be taken to ensure the sterility of the prepared solution particularly as it 
contains no antimicrobial preservatives. 
 
Other medicinal products should not be added to the MabCampath infusion solution or simultaneously 
infused though the same intravenous line. 
 
Caution should be exercised in the handling and preparation of the MabCampath solution. The use of 
latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or 
other accidental spillage. Women who are pregnant or trying to become pregnant should not handle 
MabCampath. 
 
Procedures for proper handling and disposal should be observed. Any spillage or waste material 
should be disposed of by incineration. 
 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCHRELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET