Raptiva

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1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Raptiva 100 mg/ml powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains a retrievable amount of 125 mg of efalizumab. 
Reconstitution with the solvent yields a solution containing efalizumab at 100 mg/ml. 
 
Efalizumab is a recombinant humanized monoclonal antibody produced in genetically engineered 
Chinese Hamster Ovary (CHO) cells. Efalizumab is an IgG1 kappa immunoglobulin, containing 
human constant region sequences and murine light- and heavy-chain complementary determining 
region sequences. 
 
Excipients: 2.5 mg polysorbate 20, 3.55 mg histidine, 5.70 mg histidine hydrochloride monohydrate, 
102.7 mg sucrose. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 
The powder is a white to off white cake. 
The solvent is a clear, colourless liquid. 
 
The pH of the reconstituted solution is 5.9 – 6.5. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of adult patients with moderate to severe chronic plaque psoriasis who have failed to 
respond to, or who have a contraindication to, or are intolerant to other systemic therapies including 
ciclosporin, methotrexate and PUVA (see section 5.1 – Clinical Efficacy). 
 
4.2 Posology and method of administration 
 
Treatment with Raptiva should be initiated by a physician specialised in dermatology.  
 
An initial single dose of 0.7 mg/kg body weight is given followed by weekly injections of 1.0 mg/kg 
body weight (maximum single dose should not exceed a total of 200 mg). The volume to be injected 
should be calculated as follows:  
 

Dose Volume to be injected per 
10 kg body weight 

Single initial dose: 0.7 mg/kg 0.07 ml 
Subsequent doses: 1 mg/kg 0.1 ml 

 
The duration of therapy is 12 weeks. Therapy may be continued only in patients who responded to 
treatment (PGA good or better). For discontinuation guidance see section 4.4. 
 



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Children and adolescents (< 18 years) 
Raptiva is not recommended for use in children below age 18 due to a lack of data on safety and 
efficacy. 
 
Use in the elderly (≥ 65 years) 
The dosage and administration schedule in the elderly should be the same as for adults (see also 
section 4.4). 
 
Patients with renal or hepatic impairment  
No studies have been conducted in patients with renal or hepatic impairment. Raptiva should be used 
with caution in this patient population. 
 
Method of administration 
Raptiva is for subcutaneous injection. Injection sites should be rotated. 
For instructions for use see section 6.6. 
 
After proper training in the reconstitution and injection technique, patients may self-inject with 
Raptiva, if their physician determines that this is appropriate. 
 
4.3 Contraindications 
 
Hypersensitivity to efalizumab or to any of the excipients. 
Patients with history of malignancies. 
Patients with active tuberculosis and other severe infections. 
Patients with specific forms of psoriasis like guttate, erythrodermic or pustular psoriasis as sole or 
predominant form of psoriasis. 
Patients with immunodeficiencies. 
 
4.4 Special warnings and precautions for use 
 
Effects on the immune system 
 
a) Infections 
Raptiva is a selective immunosuppressor that alters T-lymphocyte function and may affect host 
defences against infections. It has the potential to increase the risk or the severity of infections, e.g. 
tuberculous pneumonia, and reactivate latent, chronic infections e.g. JC virus infection. 
Patients developing an infection during treatment with Raptiva should be monitored and according to 
severity Raptiva should be discontinued. In a patient with history of clinically significant recurring 
infections, Raptiva should be used with caution. 
The use of Raptiva may be associated with an increased risk of Progressive Multifocal 
Leukoencephalopathy (PML). One case of JC virus infection resulting in PML has been reported in 
post-marketing surveillance in a patient with psoriasis receiving Raptiva (see section 4.8).  
 
Patients must be monitored at regular intervals for any new or worsening neurological symptoms or 
signs that may be suggestive of PML (such as impaired cognition, visual disturbances, hemiparesis, 
altered mental state or behavioural changes). If PML is suspected, further dosing must be suspended 
until PML has been excluded. The clinician should evaluate the patient to determine if the symptoms 
are indicative of neurological dysfunction, and if so, whether these symptoms are possibly suggestive 
of PML. If any doubt exists, further evaluation, including Magnetic Resonance Imaging (MRI) scan 
preferably with contrast, cerebrospinal fluid (CSF) testing for JC viral DNA and repeat neurological 
assessment, should be considered. Patients should also be advised to inform their partner or caregivers 
about their treatment, since they may notice symptoms that the patient is not aware of. 
If a patient develops PML, the dosing of Raptiva must be permanently discontinued. 
 
b) Vaccinations 
Limited data are available on the effects of vaccination. Neo-vaccinations given during treatment with 
Raptiva may induce antibody levels lower than those observed in non-treated subjects, but the clinical 



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significance of this is unknown. Patients should not receive live and live-attenuated vaccines while on 
Raptiva therapy. Before vaccination, treatment with Raptiva should be withheld for 8 weeks and can 
resume 2 weeks after vaccination. (see section 4.5). 
 
c) Malignancies and lymphoproliferative disorders 
It is not yet known whether or not Raptiva can increase the risk of lymphoproliferative disorders or 
other malignancies in psoriasis patients. Raptiva should be discontinued if a malignancy develops 
while the patient is on treatment (see sections 4.3 and 4.8). 
Raptiva has not been studied in combination with immunosuppressive systemic antipsoriasis medicinal 
products. Therefore, combination therapies with these products are not recommended (see section 4.5). 
 
Immune-mediated haemolytic anaemia 
In post-marketing surveillance, isolated cases of severe haemolytic anaemia have been reported during 
treatment with Raptiva. In such circumstances, Raptiva should be discontinued.  
 
Thrombocytopenia 
Thrombocytopenia may occur during Raptiva treatment and may be associated with clinical signs such 
as echymoses, spontaneous bruising or bleeding from muco-cutaneous tissues. If these manifestations 
occur, efalizumab should be stopped immediately, a platelet count should be performed and 
appropriate symptomatic treatment should be instituted immediately (see section 4.8). 
Platelet counts are recommended upon initiating and periodically while receiving Raptiva treatment. It 
is recommended that assessments be more frequent when initiating therapy (e.g., monthly) and may 
decrease in frequency with continued treatment (e.g., every 3 months). 
 
Inflammatory polyradiculoneuropathy 
Cases of inflammatory polyradiculoneuropathy have been observed in post-marketing surveillance in 
patients receiving Raptiva (see section 4.8). Patients have recovered after discontinuation of Raptiva, 
therefore Raptiva should be stopped following the diagnosis of inflammatory polyradiculoneuropathy. 
 
Hypersensitivity and allergic reactions 
As with any recombinant product, Raptiva is potentially immunogenic. Consequently, if any serious 
hypersensitivity or allergic reaction occurs, Raptiva should be discontinued immediately and 
appropriate therapy initiated (see sections 4.3 and 4.8). 
 
Arthritis 
Cases of arthritis have been observed during treatment or after discontinuation of Raptiva. It is 
recommended to discontinue Raptiva if arthritis occurs during treatment. 
 
Psoriasis 
During treatment with Raptiva, cases of exacerbation of psoriasis, including pustular, erythrodermic, 
and guttate subtypes, have been observed (see section 4.8). In such cases, it is recommended to 
discontinue treatment with Raptiva. 
Discontinuation of treatment may cause a recurrence or exacerbation of plaque psoriasis including 
erythrodermic and pustular psoriasis, especially in patients not responding to treatment. Gradual 
reduction of dose or frequency does not appear to be beneficial. 
 
Discontinuation 
Management of patients discontinuing Raptiva includes close observation. In case of recurrence or 
exacerbation of disease, as well as in patients who discontinue Raptiva and are non-responders, the 
treating physician should institute the most appropriate psoriasis treatment as necessary. 
In case re-treatment with Raptiva is indicated the same guidance should be followed as under 
Posology and method of administration. Re-treatment may be associated with lower or inadequate 
response to Raptiva than in the earlier treatment periods. Therapy may be continued only in those 
patients who respond adequately to treatment. 
 



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Special patient populations 
No differences in safety or efficacy were observed between elderly (≥ 65 years) patients and younger 
patients. As there is a higher incidence of infections in the elderly population in general, caution 
should be used in treating the elderly. 
Raptiva has not been studied in patients with renal or hepatic impairment and should therefore be used 
with caution in such patients. See section 4.8 regarding the effects on the hepatic function. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
There have been no formal drug interaction studies performed with Raptiva. 
 
Limited data are available on the effects of vaccination in patients receiving Raptiva.  
In a study of 66 patients with moderate plaque psoriasis, immune responses during and after Raptiva 
treatment were investigated. Following booster vaccination with tetanus toxoid (recall antigen), the 
ability to mount an immune response to the tetanus toxoid was preserved in those patients undergoing 
Raptiva therapy. After 35 days of treatment with Raptiva, the proportion of subjects treated with 
efalizumab with positive skin test reactions to Candida was significantly reduced compared with the 
placebo group. Antibody response to an experimental neo-antigen (∅X174) was reduced during 
Raptiva therapy, but began to normalize 6 weeks after discontinuation of Raptiva therapy and did not 
demonstrate tolerance induction. A pneumococcal vaccine administered 6 weeks after discontinuation 
of Raptiva yielded normal results. Neo-vaccinations given during treatment with Raptiva may induce 
antibody levels lower than non-treated subjects, but the clinical significance of this is unknown. 
Patients should not receive live and live-attenuated vaccines during Raptiva treatment. (See section 
4.4). 
 
Given the mechanism of action of efalizumab, its effects on the immune system may be potentiated by 
systemic immunosuppressives commonly used for the treatment of psoriasis (see section 4.4). 
 
Raptiva has been used in combination with topical corticosteroids in psoriasis patients without any 
untoward effects nor with any observable significant beneficial effect of the combination therapy 
above monotherapy with efalizumab. 
 
4.6 Pregnancy and lactation 
 
Pregnancy 
In general, immunoglobulins are known to cross the placental barrier. There are no adequate data from 
the use of efalizumab in pregnant women. Animal studies indicate an impairment of the immune 
function of the offspring (see section 5.3).  
 
Pregnant women should not be treated with Raptiva. 
Women of childbearing potential have to use appropriate contraception during treatment. 
 
Lactation 
Excretion of efalizumab in human milk has not been investigated, however immunoglobulins are 
expected to be excreted in human milk. Moreover, an antibody analogue of efalizumab was shown to 
be excreted in milk of mice. Women should not breastfeed during treatment with Raptiva. 
 
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. Based on the 
pharmacological mechanism of action of efalizumab, the use of Raptiva is not expected to affect 
patient’s ability to drive and use machines. 
 
4.8 Undesirable effects 
 
The most frequent symptomatic adverse drug reactions (ADRs) observed during Raptiva therapy were 
mild to moderate dose-related acute flu-like symptoms including headache, fever, chills, nausea and 



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myalgia. In large placebo-controlled clinical studies, these reactions were observed in approximately 
41% of Raptiva-treated patients and 24% in placebo-treated patients over 12 weeks of treatment. After 
initiation of therapy, these reactions were generally less frequent and occurred at similar rates to that 
seen in the placebo group from the third and subsequent weekly injections. 
Antibodies to efalizumab were detected in only 6% of patients. In this small number of patients no 
differences were observed in pharmacokinetics, pharmacodynamics, clinically noteworthy adverse 
events or clinical efficacy. 
 
Adverse events (Preferred Terms) in the overall population studied clinically with Raptiva are listed 
below by frequency of occurrence and by MedDRA System Organ Class. Within each frequency 
grouping, undesirable effects are presented in order of decreasing seriousness. 
 

System Organ Class Very 
common 
 (>1/10) 

Common 
 (>1/100<1/10) 

Uncommon 
(>1/1,000, 

<1/100) 

Rare 
(>1/10,000, 
<1/1,000) 

Very rare 
(<1/10,000) 

Not known 

Infections and 
infestations 

     Aseptic meningitis*, 
Severe infections*, 
JC virus infection 
resulting in 
progressive multifocal 
leukoencephalopathy* 

Blood and the 
lymphatic system 
disorders 

Leuko-
cytosis and 
lympho-
cytosis  

 Thrombo-
cytopenia  

  Immune mediated 
haemolytic anaemia*

Immune system 
disorders 

 Hyper-
sensitivity 
reactions 

    

Nervous system 
disorders 

  Facial palsy 
(Bell’s 
palsy) 

  Inflammatory 
polyradiculo-
neuropathy* 

Respiratory, 
thoracic and 
mediastinal 
disorders 

     Interstitial 
pneumonitis* 

Skin and 
subcutaneous tissue 
disorders 

 Psoriasis Urticaria   Erythema 
multiforme* 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Arthritis / 
Psoriatic 
arthritis 
(exacerbation/
flare) 

    

General disorders 
and administration 
site conditions 

Flu-like 
symptoms 
including 
fever, 
headaches, 
chills, 
nausea and 
myalgia  

Back pain, 
Asthenia 

Injection site 
reactions 
 

   

Investigations  Elevation of 
alkaline 
Phosphatase, 
Elevation of 
ALT  

    



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* Events identified during postmarketing surveillance 
 
The safety profile in the target population as defined in section 4.1 is similar to the safety profile in the 
overall population treated during clinical development of Raptiva as presented above. 
 
Additional Information 
 
Long-term exposure: 
Analysis following long-term use in a cohort of 339 patients with moderate to severe psoriasis 
receiving Raptiva 1 mg/kg/week, of which 166 patients have been treated for more than 2 years and up 
to 3 years, did not show any noteworthy differences in frequency of adverse events as compared to 12 
weeks of exposure to Raptiva. Leucocytosis and lymphocytosis: in large placebo-controlled and in 
long-term clinical studies, between 40 and 50% of patients developed sustained asymptomatic 
lymphocytosis during Raptiva therapy. All values were between 2.5 fold and 3.5 fold the ULN (Upper 
Limit of Normal). Lymphocyte count returned to baseline after therapy discontinuation. Slight 
elevation in absolute neutrophil count and eosinophil count were observed but in a smaller proportion 
of patients. 
 
Thrombocytopenia:  
In the combined safety database of 3291 Raptiva-treated patients at the time of approval, there were 
nine occurrences (0.3%) of thrombocytopenia with less than 52,000 cells per μl reported. Four of these 
patients had clinical signs of thrombocytopenia. Based on available platelet count measurements, the 
onset of platelet decline was between 8 and 12 weeks after the first dose of Raptiva in 5 patients, but 
occurred later in the other patients. In one patient, thrombocytopenia occurred 3 weeks after treatment 
discontinuation. Over long term treatment up to 3 years, a small and gradual decrease in mean platelet 
counts within the normal range was observed. In the same population two cases of severe 
thrombocytopenia (0.6%) of rapid onset were observed (See section 4.4). 
 
Psoriasis:  
In the first 12 weeks of placebo-controlled studies, the rate of psoriasis adverse events was 3.2% in the 
Raptiva-treated patients and 1.4% in the placebo-treated patients. Among 3291 patients in the 
combined safety database, 39 patients presented an erythrodermic or pustular psoriasis (1.2%). 
Seventeen of these events occurred after discontinuation of Raptiva, while 22 occurred during 
treatment. In the cases occurring during treatment, most of these events (16/22) occurred in patients 
presenting no response to Raptiva. Cases occurring after discontinuation were observed both in 
patients responding or not responding to Raptiva treatment. 
 
Arthritis / Psoriatic arthritis:  
In the first 12 weeks of placebo-controlled studies, arthritis and exacerbation or flare of arthritis were 
observed in 1.8% of Raptiva-treated patients and placebo-treated patients. In these studies, the 
incidence of other types of arthritis-related adverse events were similar between the Raptiva and 
placebo groups. 
 
Flu-like symptoms:  
In large placebo-controlled clinical studies, approximately 20% of patients in excess of placebo 
reported flu-like symptoms including headaches, chills, fever, nausea and myalgia. The percentage of 
patients reporting flu-like symptoms was greatest with the first injection and decreased by more than 
50% with the second injection. These symptoms diminished thereafter to a percentage comparable to 
that of patients treated with placebo. Headache was the most frequent of the flu-like symptoms. None 
of those events was serious and less than 5% were considered severe. Overall less than 1% of patients 
discontinued therapy because of acute flu-like symptoms. 
 
Hypersensitivity and allergic disorders:  
In large placebo-controlled clinical studies, the percentage of patients experiencing an adverse event 
suggestive of hypersensitivity, including urticaria, rash and allergic reactions was slightly higher in the 
Raptiva group (8%) than in the placebo group (7%). (See section 4.4). Over long term treatment, the 
frequency of hypersensitivity-related adverse events did not increase. 



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Elevation of alkaline phosphatase:  
In large placebo-controlled clinical studies approximately 4.5% of patients developed sustained 
elevation of alkaline phosphatase throughout Raptiva therapy compared to 1% in placebo patients. All 
values were between 1.5 fold and 3 fold the ULN, and returned to baseline levels after therapy 
discontinuation. 
 
Elevation of ALT: 
About 5.7% of patients developed elevation in ALT during Raptiva therapy compared to 3.5% in 
placebo. All occurrences were asymptomatic and values above 2.5 fold ULN were not more frequent 
in the Raptiva group than in the placebo group. All values returned to baseline levels upon therapy 
discontinuation. 
 
Infections:  
Other therapies that alter T-lymphocyte function have been associated with increased risk of 
developing serious infections. In placebo controlled clinical trials, infection rates in Raptiva-treated 
patients was approximately 27.3% versus 24.0% in placebo-treated patients. In the target population 
studied in study IMP24011, the infection rate in Raptiva-treated patients was approximately 25.7% 
versus 22.3% in placebo-treated patients.  
As regards serious infections, the overall incidence in both controlled and uncontrolled studies of up to 
12 weeks was 2.8 per 100 patient-years for Raptiva-treated patients compared with 1.4 per 
100 patient-years for placebo-treated patients. The most frequent serious infections were pneumonia, 
cellulitis, infections not otherwise specified and sepsis. Over long term treatment, the incidence of 
serious infection was 1.8 per 100 patient years (see section 4.). 
JC virus infection resulting in PML has been reported in post-marketing surveillance in a patient with 
psoriasis receiving Raptiva (see section 4.4). 
 
Class adverse reactions 
 
Neoplasms benign and malignant:  
A higher rate of malignancies has been associated with therapies affecting the immune system. In 
placebo controlled clinical trials, the overall incidences of malignancy (the majority of which were 
non-melanoma skin cancers) were similar in Raptiva-treated patients and in placebo-treated patients. 
In addition, the incidences of specific tumours in Raptiva patients were in line with those observed in 
control psoriasis populations.  
 
There was no evidence of an increased risk of any particular malignancy over time with the exception 
of non-melanoma skin cancer (0.3 vs. 0.9 per 100 patient-years, short term and long term treatment, 
respectively) (See section 4.4). 
 
Inflammatory polyradiculoneuropathy:  
Isolated cases have been observed during post-marketing surveillance. (See section 4.4). 
 
4.9 Overdose 
 
In a clinical study, where subjects were exposed to higher doses of efalizumab (up to 10 mg/kg 
intravenous), one subject receiving 3 mg/kg intravenous dose experienced hypertension, chills, and 
fever on the day of study drug dosing, which required hospitalization. Another subject who received 
10 mg/kg intravenous dose experienced severe vomiting following administration of efalizumab, 
which also required hospitalization. Both occurrences fully resolved without any sequelae. Doses up to 
4 mg/kg/week subcutaneously for 10 weeks have been administered without any toxic effect. 
 
There is no known antidote to Raptiva or any specific treatment for Raptiva overdose other than 
withholding treatment and patient observation. In case of overdose, it is recommended that the patient 
be monitored under close medical care and appropriate symptomatic treatment instituted immediately. 
 
 



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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: selective immunosuppressive agents, ATC code: L04AA21 
 
Mechanism of action 
Efalizumab is a recombinant humanized monoclonal antibody that binds specifically to the CD11a 
subunit of LFA-1 (lymphocyte function-associated antigen-1), a leukocyte cell surface protein. 
 
By this mechanism, efalizumab inhibits the binding of LFA-1 to ICAM-1, which interferes with T 
lymphocytes adhesion to other cell types. LFA-1 is present on activated T lymphocytes, and ICAM-1 
is up-regulated on endothelial cells and keratinocytes in psoriasis plaques. By preventing 
LFA-1/ICAM binding, efalizumab may alleviate signs and symptoms of psoriasis by inhibiting several 
stages in the immunologic cascade. 
 
Pharmacodynamic effects 
In studies using an initial dose of 0.7 mg/kg followed by 11 weekly doses of 1.0 mg/kg, efalizumab 
maximally reduced expression of CD11a on circulating T lymphocytes to approximately 15-30% of 
pre-dose baseline values and saturated CD11a to <5% of baseline available CD11a binding sites. The 
full effect was seen 24 to 48 hours after the first dose, and was maintained between weekly doses. 
Within 5 to 8 weeks following the 12th and final dose of efalizumab administered at 1.0 mg/kg/wk, 
CD11a levels returned to within a range of ±25% of baseline values. 
 
Another pharmacodynamic marker, consistent with the mechanism of action of efalizumab, was the 
increase in the absolute counts of circulating leukocytes observed during efalizumab treatment. 
Increased absolute counts were apparent within 24 hours of the first dose, remained elevated with 
weekly dosing, and returned to baseline after treatment cessation. The largest increase occurred in the 
absolute count of circulating lymphocytes. In clinical trials, mean lymphocyte counts approximately 
doubled relative to baseline in subjects receiving 1.0 mg/kg/wk of Raptiva. The increase included 
CD4 T-lymphocytes, CD8 T-lymphocytes, B-lymphocytes, and natural killer (NK) cells, although NK 
cells and CD4 cells increased less relative to other cell types. At a dose of 1.0 mg/kg/wk subcutaneous 
efalizumab, lymphocyte levels returned to within 10% of baseline by 8 weeks post last dose. 
 
Clinical efficacy 
The efficacy of Raptiva versus other systemic therapies in patients with moderate to severe psoriasis 
has not been evaluated in studies directly comparing Raptiva with other systemic therapies. The 
present results of Raptiva versus placebo over 12 weeks of treatment with different populations 
indicate a PASI 75 response to Raptiva in 22% to 39% of patients (see Table 2). Based on the clinical 
development data generated (see Table 1) and long-term experience, Raptiva is recommended for use 
in patients as defined in section 4.1.  
 
Failure on prior systemic therapies is defined as insufficient response (PASI < 50 or PGA less than 
good), or worsening of disease in patients while on treatment, and who were adequately dosed for a 
sufficiently long duration to assess response with at least each of the 3 major systemic therapies as 
available. 
 
The safety and efficacy of Raptiva in moderate to severe plaque psoriasis patients has been 
demonstrated in five randomized, double-blind, placebo-controlled trials at the recommended dose 
(n=1742). There are no comparative data with Raptiva versus other systemic psoriasis therapies. The 
largest study IMP24011 (n=793) included patients (n=526) who were not controlled by, 
contraindicated to, or intolerant to two or more systemic therapies as judged from the patients’ 
histories of psoriasis treatment. In all studies, the primary endpoint was the proportion of patients with 
a ≥ 75% improvement in the Psoriasis Area and Severity Index score (a PASI 75 response) relative to 
baseline when assessed one week after a 12-week treatment course. Secondary endpoints included the 
proportion of subjects who achieved a rating of Minimal or Clear on a static global assessment by the 
physician, the Overall Lesion Severity (OLS), the proportion of patients with a ≥ 50% improvement in 



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PASI score (a PASI 50 response) relative to baseline after 12 weeks of treatment, the time-course of 
mean PASI percentage improvement from baseline, improvement in the Dermatology Life Quality 
Index (DLQI), Psoriasis Symptom Assessment (PSA), the Physician’s Global Assessment (PGA) of 
change, change in the PASI thickness component, and change in the body surface area affected. 
 
In all five studies, patients randomized to the Raptiva group achieved statistically significantly better 
responses than placebo on the primary endpoint. The same results were confirmed in patients that were 
unsuitable for other systemic therapies (see Table 1 below). 
 

Table 1 
Primary Endpoint: Proportion of Subjects with ≥75% improvement in PASI after 12 weeks of 

Treatment (PASI 75) 
  Efalizumab a 

Patient population IMP24011 Placebo 1.0 mg/kg/wk Treatment 
Effect  

[95% CI] 
All patients 4% 

(n=264) 
31% 

(n=529) b 
27% 

[22%, 32%] 
Patients who are not controlled by, 

contraindicated to, or intolerant to two or 
more systemic therapies * 

3% 
(n=184) 

30% 
(n=342) b 

27% 
[21%, 32%] 

a p-values compared efalizumab with placebo using logistic regression including baseline 
PASI score, prior treatment for psoriasis and geographical region as covariates. 

b p<0.001. 
* As judged from the patients’ histories of psoriasis treatments 
 
In all five studies, patients randomized to the Raptiva dose group achieved statistically significantly 
better responses than placebo on the primary endpoint (PASI 75 response) (see Table 2 below) and on 
all the secondary efficacy endpoints. 
 

Table 2 
Primary Endpoint: Proportion of Subjects with ≥75% 

improvement in PASI after 12 weeks of Treatment (PASI 75)  

  Efalizumab a 
Study Placebo 1.0 mg/kg/wk Treatment Effect  

[95% CI] 
ACD2390g * 4%  

(n=187) 
27%  

(n=369) b 
22%  

[16%, 29%] 
ACD2058g 2%  

(n=170) 
39%  

(n=162) b 
37%  

[28%, 46%] 
ACD2059g * 5%  

(n=122) 
22%  

(n=232) b 
17%  

[9%, 27%] 
ACD2600g * 3%  

(n=236) 
24%  

(n=450) b 
21%  

[15%, 27%] 
IMP24011 * 4% 

(n=264) 
31% 

(n=529) b 
27% 

[22%, 32%] 



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a IMP24011: p-values compared efalizumab with placebo 
using logistic regression including baseline PASI score, 
prior treatment for psoriasis and geographical region as 
covariates. 

 Other studies: p-values compared each efalizumab group 
with placebo using Fisher’s exact test within each study. 

b
 p<0.001. 

* The efalizumab used in the study is the Genentech 
manufactured product 

 
Time to relapse (≥50% loss of improvement) was evaluated in Study ACD2058g and IMP 24011 for 
patients who were classified as responders (≥75% improvement on PASI) after 12 weeks of treatment. 
The median time to relapse among PASI responders ranged from 58 to 74 days following the last 
Raptiva dose in the initial treatment period. In study IMP24011, approximately half of the patients 
(46.8%) who were partial responders (50% to 74% improvement on PASI, similar to PGA good) after 
12 weeks of Raptiva treatment achieved a PASI 75 response at week 24. 
 
Long-term treatment: 
Data from extended treatment (more than 12 weeks) have been obtained from 4311 patients in open 
label uncontrolled studies. Over 600 patients have been treated for more than 1 year including 
166 patients treated for more than 2 years and up to 3 years. Approximately half of the patients treated 
for more than 1 year were PASI 75 responders (when all dropouts were considered as non-responders).  
 
5.2 Pharmacokinetic properties 
 
Absorption:  
After subcutaneous administration of efalizumab peak plasma concentrations are reached after 1-
2 days. Comparison with intravenous data indicated an average bioavailability of about 50% at the 
recommended dose level of 1.0 mg/kg/wk subcutaneous. 
 
Distribution:  
Steady state was achieved at week 4. At the 1 mg/kg/wk dose level (with an initial dose of 0.7 mg/kg 
the first week), mean efalizumab plasma trough values were 11.1±7.9 µg/ml. Measurements of volume 
of distribution of the central compartment after single intravenous doses were 110 ml/kg at dose 
0.03 mg/kg and 58 ml/kg at dose 10 mg/kg. 
 
Biotransformation:  
The metabolism of efalizumab is through internalisation followed by intracellular degradation as a 
consequence of either binding to cell surface CD11a or through endocytosis. The expected degradation 
products are small peptides and individual amino acids which are eliminated by glomerular filtration. 
Cytochrome P450 enzymes as well as conjugation reactions are not involved in the metabolism of 
efalizumab. 
 
Elimination: 
Efalizumab is cleared by nonlinear saturable elimination (dose dependent). Mean steady state 
clearance is 24 ml/kg/day (range 5-76 ml/kg/day) at 1 mg/kg/ week subcutaneous. 
The elimination half-life was about 5.5-10.5 days at 1 mg/kg/ week subcutaneous. Tend at steady state 
is 25 days (range 13-35 days). Weight is the most significant covariate affecting efalizumab clearance. 
 
Non-linearity: 
Efalizumab shows dose-dependent nonlinear pharmacokinetics which can be explained by its saturable 
specific binding to cell surface receptors CD11a. It appeared that the receptor mediated clearance of 
efalizumab was saturated when plasma efalizumab concentrations were above 1 μg/ml. 
 
Through population pharmacokinetic analysis, weight was found to affect efalizumab clearance. 
Covariates as baseline PASI, baseline lymphocyte count and age had modest effects on clearance; 



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gender and ethnic origin had no effect. The pharmacokinetics of efalizumab in paediatric patients have 
not been studied. The effect of renal or hepatic impairment on the pharmacokinetics of efalizumab has 
not been studied. 
 
Antibodies to efalizumab were detected in only 6% of patients evaluated. In this small number of 
patients no differences were observed in either pharmacodynamic or pharmacokinetic parameters. 
 
5.3 Preclinical safety data 
 
Efalizumab does not cross-react with CD11a from species other than humans and chimpanzees. 
Therefore, conventional non-clinical safety data with the medicinal product are limited and do not 
allow for a comprehensive safety assessment. Inhibitory effects were observed on the humoral and 
T-cell dependent immune responses. In pups of mice treated with an antibody analogue of efalizumab, 
a decrease in T-cell dependent immunity was observed up to at least 11 weeks of age. Only at 
25 weeks of age was this decrease no longer significant. 
Otherwise, the effects observed in non-clinical studies could be related to the pharmacology of 
efalizumab. 
No lymphomas were observed following 6 months treatment with an antibody analogue of efalizumab 
in a 6 months study with p53 +/+ wild type mice. 
No teratogenic effects were seen in mice during organogenesis. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder for solution for injection: 
Polysorbate 20 
Histidine 
Histidine hydrochloride monohydrate 
Sucrose 
 
Solvent:  
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
4 years. 
 
After reconstitution, an immediate use is recommended (see also section 6.4). 
 
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. 
 
From a microbiological point of view, the product should be used immediately after first opening and 
reconstitution. If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless 
reconstitution has taken place in controlled and validated aseptic conditions. Physico-chemical 
stability of the reconstituted product has been shown for 24 hours at 2°C to 8°C. 



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6.5 Nature and contents of container 
 
Powder: 
Colourless type I glass vial with a butyl rubber stopper, and aluminium seal fitted with a flip-off 
plastic cap. 
 
Solvent: 
Type I glass pre-filled syringe. 
 
Raptiva is available in: 
Packs of 1 vial of powder, 1 pre-filled syringe of solvent, 1 EasyMIX adapter for reconstitution and 
1 needle for injection. 
Packs of 4 vials of powder, 4 pre-filled syringes of solvent, 4 EasyMIX adapters for reconstitution and 
4 needles for injection. 
Packs of 12 vials of powder, 12 pre-filled syringes of solvent, 12 EasyMIX adapters for reconstitution 
and 12 needles for injection. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Raptiva is for single use only. 
 
One vial of Raptiva should be reconstituted with the solvent before use. Reconstitution of the single-
use vial with 1.3 ml of the supplied water for injections yields approximately 1.5 ml of solution to 
deliver 100 mg per 1 ml of Raptiva. The maximum retrievable dose is 125 mg per 1.25 ml of Raptiva. 
 
The solution should reconstitute in not more than 5 minutes. The reconstituted solution is a clear to 
slightly opalescent, colourless to pale yellow solution, and should not be administered if it contains 
particles or is not clear. 
 
Detailed instructions for use are provided in the package leaflet. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Serono Europe Ltd. 
56 Marsh Wall 
London E14 9TP 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/04/291/001 
EU/1/04/291/002 
EU/1/04/291/003 
 
 



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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 September 2004 
 
 
10. DATE OF REVISION OF THE TEXT 
 



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ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER(S) RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 



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A MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance 
 
Genentech, Inc. 
1 DNA Way, South San Francisco, CA 94080-4990 
USA 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Merck Serono S.p.A. 
Via L. Einaudi 11,  
00012 Guidonia Montecelio (Rome) 
Italy 
 
 
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 I: Summary of Product 
Characteristics, section 4.2) 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



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A. LABELLING 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
BOX OF 1 VIAL AND 1 PRE-FILLED SYRINGE 
BOX OF 4 VIALS AND 4 PRE-FILLED SYRINGES 
BOX OF 12 VIALS AND 12 PRE-FILLED SYRINGES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Raptiva 100 mg/ml powder and solvent for solution for injection 
Efalizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains a retrievable amount of 125 mg of efalizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Polysorbate 20, histidine, histidine hydrochloride monohydrate and sucrose. 
Solvent: water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 vial of powder for solution for injection. 
1 pre-filled syringe of 1.3 ml solvent. 
1 EasyMIX adapter for reconstitution. 
1 needle for injection. 
 
4 vials of powder for solution for injection. 
4 pre-filled syringes of 1.3 ml solvent. 
4 EasyMIX adapters for reconstitution. 
4 needles for injection. 
 
12 vials of powder for solution for injection. 
12 pre-filled syringes of 1.3 ml solvent. 
12 EasyMIX adapters for reconstitution. 
12 needles for injection. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous 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 



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8. EXPIRY DATE 
 
EXP  
 
Use immediately after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 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 

 
Discard any unused solution. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Serono Europe Ltd. 
56 Marsh Wall 
London E14 9TP 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/04/291/001  
EU/1/04/291/002 
EU/1/04/291/003 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
raptiva 100 mg/ml 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
RAPTIVA 100 mg/ml VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Raptiva 100 mg/ml 
Powder for solution for injection 
Efalizumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
125 mg retrievable 
 
 
6. OTHER 
 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SOLVENT PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for use with Raptiva 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.3 ml in pre-filled syringe 
 
 
6. OTHER 
 
 



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B. PACKAGE LEAFLET 
 

 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Raptiva 100 mg/ml powder and solvent for solution for injection 
Efalizumab 

 
 

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. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- 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 Raptiva is and what it is used for 
2. Before you use Raptiva 
3. How to use Raptiva 
4. Possible side effects 
5 How to store Raptiva 
6. Further information 
 
 
1. WHAT RAPTIVA IS AND WHAT IT IS USED FOR 
 
Raptiva is a systemic psoriasis medicine. Systemic therapies are medicines taken orally or 
administered by injection and thus will be present in and affect the whole body. 
 
Raptiva is a medicine containing efalizumab, made by means of biotechnology. It is produced by 
genetically engineered mammalian cells. Efalizumab is a monoclonal antibody. Monoclonal antibodies 
are proteins that recognise and bind to other specific proteins of the human body. Efalizumab reduces 
inflammation of the psoriatic lesions which results in improvement of the affected areas of the skin.  
 
Therapeutic indications 
Treatment of adult patients with moderate to severe chronic plaque psoriasis who have failed to 
respond to, or who have a contraindication to, or are intolerant to other systemic therapies including 
ciclosporin, methotrexate and PUVA.  
This restriction of the indication of Raptiva is based on the present efficacy data and limited long-term 
experience with Raptiva.  
 
 
2. BEFORE YOU USE RAPTIVA 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Do not use Raptiva: 
- If you are allergic (hypersensitive) to efalizumab or any of the other ingredients of Raptiva. 
- If you have or have had any cancer.  
- If you have active tuberculosis or other severe infections. Symptoms that might indicate that 

you have an infection are fever, wounds, feeling tired, dental problems, a bad cough that lasts 
longer than 2 weeks, pain in the chest or coughing up blood or sputum. 

- If you have forms of psoriasis other than plaque psoriasis (for instance other more severe forms 
of psoriasis, as diagnosed by your doctor). 

- If you have been diagnosed as having a disorder of your immune system. 
 

It is important that you tell your doctor if you have had or you have any of the above.  
 



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Take special care with Raptiva: 
- If you experience hypersensitivity or allergic reactions such as overall body itching, hives, skin 

flushing or rash tell your doctor immediately or go to the local casualty. 
- You might get infections more easily. If you develop a new infection or notice any new or 

sudden change in thinking, balance, strength, talking, walking or vision, please contact your 
doctor. He/she will determine whether to monitor your treatment or whether it is necessary for 
you to stop using Raptiva.  

- If you develop cancer while undergoing treatment, please contact your doctor who will 
determine if it is necessary for you to stop using Raptiva. 

- If you develop signs and symptoms associated with anaemia (a reduction in red blood cells 
which can make the skin pale and cause weakness or breathlessness) while undergoing 
treatment, please contact your doctor who will determine if it is necessary for you to stop using 
Raptiva. 

- If you develop any of the signs and symptoms associated with a decrease in blood platelets, 
such as easy bleeding from the gums, bruising or pinpoint red spots on the skin, please tell your 
doctor immediately. He/she will determine whether to monitor your treatment or whether it is 
necessary for you to stop using Raptiva. 

- Some patients had reactions including headache, fever, nausea and vomiting within two days of 
each of the first two injections. These reactions were largely mild to moderate. If you notice that 
any of these reactions do not vanish after the second injection, tell your doctor. 

- If you discontinue Raptiva treatment (and this applies especially to patients not responding to 
treatment) your psoriasis may significantly worsen. Your doctor may wish to monitor you and 
provide effective treatment. 

- If you experience a worsening of your psoriasis or you develop arthritis, please inform your 
doctor. He/she will determine whether to stop using Raptiva or continue treatment with closer 
observation. 

- If you are going to receive any vaccine, please check with your doctor. You must not receive 
certain types of vaccines during Raptiva treatment. It may be necessary to discontinue Raptiva 
treatment 8 weeks before a vaccination. 

- If your weight changes unexpectedly, please contact your doctor. He/she will calculate the 
correct dosage based on your new weight. 

 
Tell your doctor if you have renal or hepatic impairment. 
 
Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
Please check with your doctor if you are planning to receive any vaccine (see “Take special care with 
Raptiva”).  
When taking Raptiva you might be more vulnerable to infections (see Take special care with Raptiva) 
this effect might be enhanced by other medicines that are used to treat psoriasis and that also make you 
more vulnerable to infections. Please check with your doctor if you receive other medicines to treat 
your psoriasis.  
Raptiva can be used in combination with topical corticosteroids.  
 
Pregnancy 
It is not known whether Raptiva can cause harm to your baby if you are pregnant or whether it can 
affect your ability to become pregnant. Therefore, if you are pregnant, consult with your doctor 
immediately. 
If you are a woman of childbearing potential, you are advised not to become pregnant and to use 
adequate contraception while using Raptiva. 
 
Breast-feeding 
It is possible that efalizumab is excreted in human milk. If you are breastfeeding, your doctor will 
advise you either to discontinue breastfeeding or to discontinue Raptiva while breastfeeding. 
 



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Driving and using machines 
The use of Raptiva is not expected to affect your ability to drive and use machines. 
 
 
3. HOW TO USE RAPTIVA 
 
Always take Raptiva exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure.  
 
Dosing for adults (18-64 years) and the elderly (≥ 65 years) 
The usual dose is an initial single injection of 0.7 mg/kg followed by weekly injections of 1.0 mg/kg. 
Your doctor will tell you how much you should inject. The duration of therapy is 12 weeks. Therapy 
may be continued only in patients who responded to treatment, your doctor will discuss with you the 
extent of your response to treatment. 
 
Method and route of administration 
Raptiva is injected just under the skin (subcutaneous). It is for single use only. The injection can be 
self-administered or given by another person, for example a family member or your doctor. You 
should continue to inject Raptiva as long as instructed to do so by your doctor. 
 
The vial of powder is designed to be reconstituted (mixed) with the solvent. 
 
If you administer Raptiva, please read the following instructions carefully and follow then step by 
step: 
• Wash your hands. It is important that your hands and items you use be as clean as possible. 
• Take the Raptiva out of the refrigerator and lay out on a clean surface everything you need: 

o one vial containing the Raptiva powder 
o one pre-filled syringe containing the solvent 
o one EasyMIX adapter for reconstitution 
o two alcohol swabs 
o one needle for subcutaneous injection, and 
o a sharps container 
 

• Remove the protective cap from the Raptiva vial and from the solvent pre-filled syringe. Wipe 
the top of the vial with an alcohol swab.  

• Holding the EasyMIX outer cover, carefully peel back and remove the protective film using the 
tab. This will expose a plastic spiked end that you will use to pierce the vial. You should not 
touch this area. 

• Holding the EasyMIX outer cover, place it on top of the vial, then press down so that the plastic 
spiked end pierces the rubber stopper on the vial. 

• Ensure the EasyMIX adapter is firmly attached to the vial, before removing the outer cover.  
 
 
 
 
 
 
 
 
 



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• Pull off the cap covering the pre-filled syringe tip.  
• Attach the pre-filled syringe containing the solvent to the EasyMIX adapter with a ‘push and 

twist’ action. 
 
 
 
 
 
 
 
 
• Very slowly push down on the syringe plunger to inject all the solvent into the Raptiva vial. 
• Without removing the syringe, gently rotate the vial to dissolve the medicine in the solvent.  
 
 
 
 
 
 
 
 
Do not shake (Shaking will cause foaming of the Raptiva solution). Generally reconstitution takes less 
than 5 minutes. After the powder has dissolved, check the resulting solution for particles and 
discoloration. The reconstituted solution should be clear to pale yellow and free of particles. No other 
medicines should be added to the solution containing Raptiva and Raptiva should not be reconstituted 
with other solvents. 
• Turn the vial upside down, with the syringe still attached. Withdraw the solution slowly into the 

syringe, taking more than the dose you need. Some foam or bubbles may remain in the vial. 
 With the syringe still attached to the vial, check the syringe for air bubbles.  
• Gently tap the syringe to make any bubbles rise to the top of the syringe.  
 
 
 
 
 
 
 
 
 
• Gently push the plunger up until the dose to be given remains in the syringe. This will also push 

the bubbles out of the syringe and into the vial. If you eject too much Raptiva back into the vial, 
simply repeat the drawing up process and continue. 

 
 
 
 
 
 
 
 
 
 
• Check you have the right dose, then remove the syringe from the EasyMIX adapter using a 

‘twist and pull’ action. 
 



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You are now ready to attach the injection needle. 
• Take the injection needle and, with its shield still in place, carefully screw it on to the syringe 

tip. 
 
You are now ready to select and prepare your injection site. Your doctor or nurse will have already 
advised you where to inject. Sites for self-injection include the buttocks, thigh, abdomen or upper arm. 
The injection sites should be rotated.  
• Wipe the chosen area with an alcohol swab. Remove the shield from the injection needle. 
• Immediately inject the solution as follows: Firmly pinch the skin together and insert the needle 

at a 45° to 90° angle using a dart-like motion. Inject under the skin, as you were taught. Do not 
inject directly into a vein. Pull back the plunger very slightly. If blood comes into the syringe, 
the needle has entered a blood vessel. Do not inject but withdraw the needle and repeat the 
injection procedure. Inject the solution by pushing gently on the plunger. Take as much time as 
you need to inject all the solution. Immediately withdraw the needle and clean the skin with an 
alcohol swab using a circular motion. 

 

• Dispose of all used items: Once you have finished your injection, immediately discard all 
needles and empty glass containers in a sharps container. Any unused solution must be 
discarded. 

 
If you use more Raptiva than you should 
If you have injected more Raptiva than told by your doctor, please contact your doctor or pharmacist. 
It is recommended that you are monitored for any signs or symptoms of adverse effects and that you 
are given appropriate symptomatic treatment immediately. 
 
If you forget to use Raptiva 
Do not take a double dose to make up for a forgotten dose. 
Please contact your doctor if you forget to take 2 or more doses of Raptiva. 
 
If you stop using Raptiva 
If you discontinue treatment with Raptiva without substitution treatment, your psoriasis may 
significantly worsen. (See “Take special care with Raptiva”) 
 
In case re-treatment with Raptiva is needed you should follow the guidance of your doctor. Re-
treatment may be associated with lower or inadequate response to Raptiva than in the earlier treatment 
periods. Therapy should be continued only when adequate response is observed. Your doctor will 
advise you what to do when insufficient response to treatment or worsening of your disease is 
observed. (See also under Take Special Care with Raptiva) 
 
If you have any further questions on the use of the product, ask your doctor or pharmacist. 
 
 



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4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Raptiva can cause side effects, although not everybody gets them. 
 
The side effects in this section are given with an estimation of the frequency with which they may 
occur. For this purpose the following classification has been used: 
• Very common: Side effects that may occur in more than 1 out of 10 patients; 
• Common: Side effects that may occur in 1 to 10 out of 100 patients; 
• Uncommon: Side effects that may occur in 1 to 10 out of 1,000 patients; 
• Rare: Side effects that may occur in 1 to 10 out of 10,000 patients; 
• Very rare: Side effects that may occur in less than 1 out of 10,000 patients; 
 
Raptiva may cause mild to moderate flu-like symptoms including headache, chills, nausea, muscle 
aches and occasionally fever within 48 hours of an injection of Raptiva. These symptoms are very 
common and occur most often after the first two doses and decrease with continued use. If any of these 
symptoms are severe or persist, you should contact your doctor. In clinical trials, visible side effects at 
the injection site and injection site pain were uncommon. 
 
Tell your doctor or go to the local casualty and stop using Raptiva immediately if you:  
• Notice serious hypersensitivity or allergic reactions, such as anaphylaxis. Symptoms of an 

allergic reaction are common and generally include overall body itching, hives, skin flushing or 
rash. Anaphylaxis is a more serious allergic reaction that may involve dizziness, vomiting, low 
blood pressure, and difficulty with breathing. Prompt medical care is needed since serious 
allergic reactions may be potentially life-threatening. 

• Notice symptoms of low blood platelet counts, such as easy bleeding from the gums, bruising or 
pinpoint red spots on the skin. These symptoms are uncommon.  

• Notice signs of nerve disorder such as tingling or onset of weakness in legs or arms or new or 
sudden change in thinking, balance, strength, talking, walking or vision. 

• Notice severe headache accompanied with nuchal rigidity. This may occur rarely in particular at 
the beginning of the treatment. 

• Are diagnosed with cancer.  
• Develop a diffuse skin rash or blisters in your oral cavity. 
 
Tell your doctor and discuss with him your general health if you notice any of the following: 
• Back pain, joints pain, headache, vomiting, weakness, fatigue or rash. These common side 

effects have not been clearly associated with Raptiva but have been observed when using it. 
Your doctor may want to examine you more closely and ask you to have blood tests. 

• Fever or if you think that you have an infection. Raptiva acts on the immune system, which may 
potentially increase your risk of infectious diseases or may reactivate old infections. Infections 
are very common.  

• A relapse or flare or strong worsening of psoriasis or red, inflamed psoriatic plaques, sometimes 
with swelling of your arms or legs or joint inflammation, especially after stopping Raptiva. 
These side effects are common. 

• Shortness of breath or any persistent respiratory difficulties. 
• Signs of facial paralysis usually on one side of the face (such as weakness of face muscles and 

dribbling) possibly preceded by pain in the ear area. Generally patients with facial paralysis 
recover within a few weeks without any specific treatment. 

 
Certain laboratory tests may change, such as the number of white or red blood cells (including 
leukocytes and lymphocytes) as well as alkaline phosphatase and ALT values (blood laboratory 
values). These changes, which may be associated with the use of Raptiva, can usually only be detected 
with blood tests. 
 
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. 
 



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5. HOW TO STORE RAPTIVA 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
 
Store in the original package in order to protect from light. 
 
Do not use Raptiva after the expiry date which is stated on the label and carton after EXP. The expiry 
date refers to the last day of that month. 
 
Do not use if you notice that the solution is not clear or contains particles. 
 
To maintain sterility, Raptiva must be used immediately after first opening and reconstitution.  
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Raptiva contains 
• The active substance is efalizumab, each vial contains a deliverable dose of 125 mg efalizumab.  
• The other ingredients are polysorbate 20, histidine, histidine hydrochloride monohydrate and 

sucrose. 
• Each pre-filled syringe of solvent contains sufficient water for injections to make up the solution 

for injection.  
 
What Raptiva looks like and contents of the pack 
Raptiva is presented as a powder and solvent for solution for injection. The powder is a white to 
off-white cake and the solvent is a colourless liquid. The product is supplied in packs of 1 vial of 
powder, 1 pre-filled syringe of solvent, 1 EasyMIX adapter for reconstitution, 1 needle for injection; in 
packs of 4 vials of powder, 4 pre-filled syringes of solvent, 4 EasyMIX adapters for reconstitution, 4 
needles for injection and in packs of 12 vials of powder, 12 pre-filled syringes of solvent, 12 EasyMIX 
adapters for reconstitution and 12 needles for injection. Not all pack sizes may be available in each 
country. 
 
Marketing Authorisation Holder 
Serono Europe Ltd. 
56 Marsh Wall 
London E14 9TP 
United Kingdom 
 
Manufacturer 
Merck Serono S.p.A. 
Via Luigi Einaudi 11  
00012 Guidonia Montecelio/Rome 
Italy 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 



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België/Belgique/Belgien 
MERCK NV/SA 
Brusselsesteenweg 288 
B-3090 Overijse 
Tél/Tel: +32-2-686 07 11 

Luxembourg/Luxemburg  
MERCK NV/SA 
Brusselsesteenweg 288 
B-3090 Overijse, Belgique/Belgien 
Tél/Tel: +32-2-686 07 11 
 

България 
MERCK d.o.o.  
Dunajska cesta 119 
SI 1000 Любляна, Словения  
Teл: +386 1 560 3 800 
 

Magyarország 
Merck Kft.  
Bocskai út 134-146. 
H-1113 Budapest 
Tel: +36-1-463-8100 

Česká republika 
Merck spol.s.r.o 
Zděbradská 72 
CZ-251 01 Říčany- Jažlovice 
Tel. +420 323619211 

Malta 
Cherubino Ltd  
Delf Building 
Sliema Road 
MT-GZR 06 Gzira Malta 
Tel: +356-21-343270/1/2/3/4 
 

Danmark 
E. Merck AB 
Strandvejen 102 B, 4th 
DK-2900 Hellerup 
Tlf: +45 35253550 
 

Nederland 
Serono Benelux BV 
Tupolevlaan 41-61 
NL-1119 NW Schiphol-Rijk 
Tel: +31-20-6582800 

Deutschland 
Serono GmbH 
Alsfelder Straße 17 
D-64289 Darmstadt 
Tel: +49-6151-6285-0 
 

Norge 
Merck Serono Norge  
Luhrtoppen 2 
1470 Lørenskog 
Tlf: +47 67 90 35 90 
 

Eesti 
Merck Serono 
Esindaja  
C/o Ares Trading SA Baltic States  
Zamenhofo 11-3, LT-44287  
Kaunas, Leedu  
Tel: +370 37320603 
 

Österreich 
Merck GesmbH. 
Zimbagasse 5 
A-1147 Wien 
Tel: +43 1 57600-0 
 

Ελλάδα 
Merck A.E. 
Κηφισίας 41-45, Κτίριο Β 
GR-151 23 Μαρούσι 
Αθήνα 
Tηλ: +30-210-61 65 100 

Polska 
Merck Sp. z o.o. 
Al. Jerozolimskie 178 
02-486 Warszawa 
Polska 
Tel.: +48 22 53 59 700 
 



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España 
Merck Farma y Química, S.L. 
María de Molina, 40 
E-28006 Madrid 
Línea de Información: 900 200 400 
Tel: +34-91-745 44 00 
 

Portugal 
Merck, s.a. 
Rua Alfredo da Silva, 3-C 
P-1300-040 Lisboa 
Tel: +351-21-361 35 00 
 

France 
Merck Lipha Santé s.a.s. 
37, rue Saint-Romain 
F-69379 Lyon cedex 08 
Tél.: +33-4-72 78 25 25 
Numéro vert : 0 800 888 024 
 

România 
MERCK d.o.o.,  
Dunajska cesta 119 
SI-1000 Lubliana, Slovenia  
Tel: +386 1 560 3 800 

Ireland 
Merck Serono Ltd 
Bedfont Cross, Stanwell Road 
Feltham, Middlesex TW14 8NX  
United Kingdom 
Tel: +44-20 8818 7200 
 

Slovenija 
MERCK d.o.o. 
Dunajska cesta 119 
SI-1000 Ljubljana 
Tel: +386 1 560 3 800 
 

Ísland 
Gróco ehf. 
Þverholti 14 
IS-105 Reykjavík 
Sími: +354-568-8533 
 

Slovenská republika 
Merck spol. s r.o. 
Tuhovská 3 
SK-831 06 Bratislava 
Tel: + 421 2 49 267 111 
 

Italia 
Merck Serono S.p.A. 
Via Casilina 125 
I-00176 Roma 
Tel: +39-06-70 38 41 
 

Suomi/Finland 
Merck Oy 
Pihatörmä 1 C 
FI-02240 Espoo 
Puh/Tel: +358-9-8678 700 

Κύπρος 
Akis Panayiotou & Son Ltd 
Γιάννου Κρανιδιώτη 4 
CY-225 78, Λευκωσία 
Τηλ: +357-22677038 
 

Sverige 
E. Merck AB 
S-195 87 Stockholm 
Tel: +46-8-562 445 00 

Latvija  
Merck Serono 
Pārstāvniecība 
C/o Ares Trading SA Baltic States  
Zamenhofo 11-3,  
LT-44287 Kauņa, Lietuva 
Tel: +370 37320603 
 

United Kingdom  
Merck Serono Ltd 
Bedfont Cross, Stanwell Road 
Feltham, Middlesex TW14 8NX 
Tel: +44-20 8818 7200 

Lietuva 
Merck Serono  
Atstovybė  
C/o Ares Trading SA Baltic States  
Zamenhofo 11-3, 
LT-44287 Kaunas 
Tel: +370 37320603 

 

 
This leaflet was last approved on  


	SUMMARY OF PRODUCT CHARACTERISTICS
	A MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
	B CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET