Lucentis

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 

Lucentis 10 mg/ml solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One ml contains 10 mg ranibizumab*. Each vial contains 2.3 mg of ranibizumab in 0.23 ml solution. 

This provides a usable amount to deliver a single dose of 0.05 ml containing 0.5 mg ranibizumab to 

adult patients and a single dose of 0.02 ml containing 0.2 mg ranibizumab to preterm infants. 

 

*Ranibizumab is a humanised monoclonal antibody fragment produced in Escherichia coli cells by 

recombinant DNA technology. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection. 

 

Clear, colourless to pale yellow aqueous solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Lucentis is indicated in adults for: 

 The treatment of neovascular (wet) age-related macular degeneration (AMD) 

 The treatment of visual impairment due to diabetic macular oedema (DME) 

 The treatment of proliferative diabetic retinopathy (PDR) 

 The treatment of visual impairment due to macular oedema secondary to retinal vein occlusion 
(branch RVO or central RVO) 

 The treatment of visual impairment due to choroidal neovascularisation (CNV) 
 

Lucentis is indicated in preterm infants for: 

 The treatment of retinopathy of prematurity (ROP) with zone I (stage 1+, 2+, 3 or 3+), zone II 
(stage 3+) or AP-ROP (aggressive posterior ROP) disease. 

 

4.2 Posology and method of administration 

 

Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections. 

 

Posology 

 

Adults 

The recommended dose for Lucentis in adults is 0.5 mg given as a single intravitreal injection. This 

corresponds to an injection volume of 0.05 ml. The interval between two doses injected into the same 

eye should be at least four weeks. 

 

Treatment in adults is initiated with one injection per month until maximum visual acuity is achieved 

and/or there are no signs of disease activity i.e. no change in visual acuity and in other signs and 

symptoms of the disease under continued treatment. In patients with wet AMD, DME, PDR and RVO, 

initially, three or more consecutive, monthly injections may be needed. 

 



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Thereafter, monitoring and treatment intervals should be determined by the physician and should be 

based on disease activity, as assessed by visual acuity and/or anatomical parameters. 

 

If, in the physician’s opinion, visual and anatomic parameters indicate that the patient is not benefiting 

from continued treatment, Lucentis should be discontinued. 

 

Monitoring for disease activity may include clinical examination, functional testing or imaging 

techniques (e.g. optical coherence tomography or fluorescein angiography). 

 

If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is 

achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise 

until signs of disease activity or visual impairment recur. The treatment interval should be extended by 

no more than two weeks at a time for wet AMD and may be extended by up to one month at a time for 

DME. For PDR and RVO, treatment intervals may also be gradually extended, however there are 

insufficient data to conclude on the length of these intervals. If disease activity recurs, the treatment 

interval should be shortened accordingly. 

 

The treatment of visual impairment due to CNV should be determined individually per patient based 

on disease activity. Some patients may only need one injection during the first 12 months; others may 

need more frequent treatment, including a monthly injection. For CNV secondary to pathologic 

myopia (PM), many patients may only need one or two injections during the first year (see 

section 5.1). 

 

Lucentis and laser photocoagulation in DME and in macular oedema secondary to BRVO 

There is some experience of Lucentis administered concomitantly with laser photocoagulation (see 

section 5.1). When given on the same day, Lucentis should be administered at least 30 minutes after 

laser photocoagulation. Lucentis can be administered in patients who have received previous laser 

photocoagulation. 

 

Lucentis and verteporfin photodynamic therapy in CNV secondary to PM 

There is no experience of concomitant administration of Lucentis and verteporfin. 
 

Preterm infants 

The recommended dose for Lucentis in preterm infants is 0.2 mg given as an intravitreal injection. 

This corresponds to an injection volume of 0.02 ml. In preterm infants treatment of ROP is initiated 

with a single injection per eye and may be given bilaterally on the same day. In total, up to three 

injections per eye may be administered within six months of treatment initiation if there are signs of 

disease activity. Most patients (78%) in the clinical study received one injection per eye. The 

administration of more than three injections per eye has not been studied. The interval between two 

doses injected into the same eye should be at least four weeks. 

 

Special populations 

Hepatic impairment 

Lucentis has not been studied in patients with hepatic impairment. However, no special considerations 

are needed in this population. 

 

Renal impairment 

Dose adjustment is not needed in patients with renal impairment (see section 5.2). 

 

Elderly 

No dose adjustment is required in the elderly. There is limited experience in patients older than 

75 years with DME. 

 



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Paediatric population 

The safety and efficacy of Lucentis in children and adolescents below 18 years of age for indications 

other than retinopathy of prematurity have not been established. Available data in adolescent patients 

aged 12 to 17 years with visual impairment due to CNV are described in section 5.1 but no 

recommendation on a posology can be made. 

 

Method of administration 

 

Single-use vial for intravitreal use only. 

 

Since the volume contained in the vial (0.23 ml) is greater than the recommended dose (0.05 ml for 

adults and 0.02 ml for preterm infants), a portion of the volume contained in the vial must be discarded 

prior to administration. 

 

Lucentis should be inspected visually for particulate matter and discoloration prior to administration. 

 

For information on preparation of Lucentis, see section 6.6. 

 

The injection procedure should be carried out under aseptic conditions, which includes the use of 

surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent) 

and the availability of sterile paracentesis (if required). The patient’s medical history for 

hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure 

(see section 4.4). Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the 

periocular skin, eyelid and ocular surface should be administered prior to the injection, in accordance 

with local practice. 

 

Adults 

In adults the injection needle should be inserted 3.5-4.0 mm posterior to the limbus into the vitreous 

cavity, avoiding the horizontal meridian and aiming towards the centre of the globe. The injection 

volume of 0.05 ml is then delivered; a different scleral site should be used for subsequent injections. 

 

Paediatric population 

For treatment of preterm infants the low volume high accuracy syringe provided together with an 

injection needle (30G x ½″) in the VISISURE kit should be used (see also section 6.6). 

 

In preterm infants, the injection needle should be inserted into the eye 1.0 to 2.0 mm posterior to the 

limbus, with the needle pointing towards the optic nerve. The injection volume of 0.02 ml is then 

delivered. 
 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Patients with active or suspected ocular or periocular infections. 

 

Patients with active severe intraocular inflammation. 

 

4.4 Special warnings and precautions for use 
 

Intravitreal injection-related reactions 

 

Intravitreous injections, including those with Lucentis, have been associated with endophthalmitis, 

intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic 

cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering 

Lucentis. In addition, patients should be monitored during the week following the injection to permit 

early treatment if an infection occurs. Patients should be instructed to report any symptoms suggestive 

of endophthalmitis or any of the above mentioned events without delay. 



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Intraocular pressure increases 

 

In adults transient increases in intraocular pressure (IOP) have been seen within 60 minutes of 

injection of Lucentis. Sustained IOP increases have also been identified (see section 4.8). Both 

intraocular pressure and the perfusion of the optic nerve head must be monitored and managed 

appropriately. 

 

Patients should be informed of the symptoms of these potential adverse reactions and instructed to 

inform their physician if they develop signs such as eye pain or increased discomfort, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in their vision, or 

increased sensitivity to light (see section 4.8). 

 

Bilateral treatment 

 

Limited data on bilateral use of Lucentis (including same-day administration) do not suggest an 

increased risk of systemic adverse events compared with unilateral treatment. 

 

Immunogenicity 

 

There is a potential for immunogenicity with Lucentis. Since there is a potential for an increased 

systemic exposure in subjects with DME, an increased risk for developing hypersensitivity in this 

patient population cannot be excluded. Patients should also be instructed to report if an intraocular 

inflammation increases in severity, which may be a clinical sign attributable to intraocular antibody 

formation. 

 

Concomitant use of other anti-VEGF (vascular endothelial growth factor) 

 

Lucentis should not be administered concurrently with other anti-VEGF medicinal products (systemic 

or ocular). 

 

Withholding Lucentis in adults 

 

The dose should be withheld and treatment should not be resumed earlier than the next scheduled 

treatment in the event of: 

 a decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared with the last 
assessment of visual acuity; 

 an intraocular pressure of ≥30 mmHg; 

 a retinal break; 

 a subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is 
≥50%, of the total lesion area; 

 performed or planned intraocular surgery within the previous or next 28 days. 
 

Retinal pigment epithelial tear 

 

Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF 

therapy for wet AMD and potentially also other forms of CNV, include a large and/or high pigment 

epithelial retinal detachment. When initiating ranibizumab therapy, caution should be used in patients 

with these risk factors for retinal pigment epithelial tears. 

 

Rhegmatogenous retinal detachment or macular holes in adults 

 

Treatment should be discontinued in subjects with rhegmatogenous retinal detachment or stage 3 or 4 

macular holes. 

 



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Paediatric population 

 

The warnings and precautions for adults also apply to preterm infants with ROP. The long-term safety 

profile in preterm infants has not been established. 

 

Populations with limited data 

 

There is only limited experience in the treatment of subjects with DME due to type I diabetes. 

Lucentis has not been studied in patients who have previously received intravitreal injections, in 

patients with active systemic infections, or in patients with concurrent eye conditions such as retinal 

detachment or macular hole. There is limited experience of treatment with Lucentis in diabetic patients 

with an HbA1c over 108 mmol/mol (12%) and no experience in patients with uncontrolled 

hypertension. This lack of information should be considered by the physician when treating such 

patients. 

 

There are insufficient data to conclude on the effect of Lucentis in patients with RVO presenting 

irreversible ischaemic visual function loss. 

 

In patients with PM, there are limited data on the effect of Lucentis in patients who have previously 

undergone unsuccessful verteporfin photodynamic therapy (vPDT) treatment. Also, while a consistent 

effect was observed in subjects with subfoveal and juxtafoveal lesions, there are insufficient data to 

conclude on the effect of Lucentis in PM subjects with extrafoveal lesions. 

 

Systemic effects following intravitreal use 

 

Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have 

been reported following intravitreal injection of VEGF inhibitors. 

 

There are limited data on safety in the treatment of DME, macular oedema due to RVO and CNV 

secondary to PM patients with prior history of stroke or transient ischaemic attacks. Caution should be 

exercised when treating such patients (see section 4.8). 
 

4.5 Interaction with other medicinal products and other forms of interaction 
 

No formal interaction studies have been performed. 

 

For the adjunctive use of verteporfin photodynamic therapy (PDT) and Lucentis in wet AMD and PM, 

see section 5.1. 

 

For the adjunctive use of laser photocoagulation and Lucentis in DME and BRVO, see sections 4.2 

and 5.1. 

 

In clinical studies for the treatment of visual impairment due to DME, the outcome with regard to 

visual acuity or central retinal subfield thickness (CSFT) in patients treated with Lucentis was not 

affected by concomitant treatment with thiazolidinediones. 

 

Paediatric population 

 

No interaction studies have been performed. 

 

  



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4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential/contraception in females 

 

Women of childbearing potential should use effective contraception during treatment. 

 

Pregnancy 

 

For ranibizumab no clinical data on exposed pregnancies are available. Studies in cynomolgus 

monkeys do not indicate direct or indirect harmful effects with respect to pregnancy or 

embryonal/foetal development (see section 5.3). The systemic exposure to ranibizumab is low after 

ocular administration, but due to its mechanism of action, ranibizumab must be regarded as potentially 

teratogenic and embryo-/foetotoxic. Therefore, ranibizumab should not be used during pregnancy 

unless the expected benefit outweighs the potential risk to the foetus. For women who wish to become 

pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the 

last dose of ranibizumab before conceiving a child. 

 

Breast-feeding 

 

It is unknown whether Lucentis is excreted in human milk. Breast-feeding is not recommended during 

the use of Lucentis. 

 

Fertility 

 

There are no data available on fertility. 

 

4.7 Effects on ability to drive and use machines 
 

The treatment procedure may induce temporary visual disturbances, which may affect the ability to 

drive or use machines (see section 4.8). Patients who experience these signs must not drive or use 

machines until these temporary visual disturbances subside. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The majority of adverse reactions reported following administration of Lucentis are related to the 

intravitreal injection procedure. 

 

The most frequently reported ocular adverse reactions following injection of Lucentis are: eye pain, 

ocular hyperaemia, increased intraocular pressure, vitritis, vitreous detachment, retinal haemorrhage, 

visual disturbance, vitreous floaters, conjunctival haemorrhage, eye irritation, foreign body sensation 

in eyes, increased lacrimation, blepharitis, dry eye and eye pruritus. 

 

The most frequently reported non-ocular adverse reactions are headache, nasopharyngitis and 

arthralgia. 

 

Less frequently reported, but more serious, adverse reactions include endophthalmitis, blindness, 
retinal detachment, retinal tear and iatrogenic traumatic cataract (see section 4.4). 

 

The adverse reactions experienced following administration of Lucentis in clinical trials are 

summarised in the table below. 

 



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Tabulated list of adverse reactions# 

 

The adverse reactions are listed by system organ class and frequency using the following convention: 

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), not known (cannot be estimated from the available data). Within 

each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 

 

Infections and infestations  

Very common Nasopharyngitis 

Common Urinary tract infection* 

  

Blood and lymphatic system disorders 

Common Anaemia 

  

Immune system disorders  

Common Hypersensitivity 

  

Psychiatric disorders  

Common Anxiety 

  

Nervous system disorders  

Very common Headache 

  

Eye disorders  

Very common Vitritis, vitreous detachment, retinal haemorrhage, visual 

disturbance, eye pain, vitreous floaters, conjunctival 

haemorrhage, eye irritation, foreign body sensation in eyes, 

lacrimation increased, blepharitis, dry eye, ocular hyperaemia, 

eye pruritus. 

Common Retinal degeneration, retinal disorder, retinal detachment, 

retinal tear, detachment of the retinal pigment epithelium, 

retinal pigment epithelium tear, visual acuity reduced, vitreous 

haemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, 

cataract, cataract subcapsular, posterior capsule opacification, 

punctuate keratitis, corneal abrasion, anterior chamber flare, 

vision blurred, injection site haemorrhage, eye haemorrhage, 

conjunctivitis, conjunctivitis allergic, eye discharge, photopsia, 

photophobia, ocular discomfort, eyelid oedema, eyelid pain, 

conjunctival hyperaemia. 

Uncommon Blindness, endophthalmitis, hypopyon, hyphaema, 

keratopathy, iris adhesion, corneal deposits, corneal oedema, 

corneal striae, injection site pain, injection site irritation, 

abnormal sensation in eye, eyelid irritation. 

  

Respiratory, thoracic and mediastinal disorders 

Common Cough 

  

Gastrointestinal disorders  

Common Nausea 

  
Skin and subcutaneous tissue disorders 

Common Allergic reactions (rash, urticaria, pruritus, erythema) 

  



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Musculoskeletal and connective tissue disorders 

Very common Arthralgia 

  

Investigations  

Very common Intraocular pressure increased 
# Adverse reactions were defined as adverse events (in at least 0.5 percentage points of patients) 

which occurred at a higher rate (at least 2 percentage points) in patients receiving treatment with 

Lucentis 0.5 mg than in those receiving control treatment (sham or verteporfin PDT). 

* observed only in DME population 

 

Product-class-related adverse reactions 

 

In the wet AMD phase III studies, the overall frequency of non-ocular haemorrhages, an adverse event 

potentially related to systemic VEGF (vascular endothelial growth factor) inhibition, was slightly 

increased in ranibizumab-treated patients. However, there was no consistent pattern among the 

different haemorrhages. There is a theoretical risk of arterial thromboembolic events, including stroke 

and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of 

arterial thromboembolic events was observed in the Lucentis clinical trials in patients with AMD, 

DME, PDR, RVO and CNV and there were no major differences between the groups treated with 

ranibizumab compared to control. 

 

Paediatric population 

 

The safety of Lucentis 0.2 mg was studied in a 6-month clinical trial (RAINBOW), which included 

73 preterm infants with ROP treated with ranibizumab 0.2 mg (see section 5.1). Ocular adverse 

reactions reported in more than one patient treated with ranibizumab 0.2 mg were retinal haemorrhage 

and conjunctival haemorrhage. Non-ocular adverse reactions reported in more than one patient treated 

with ranibizumab 0.2 mg were nasopharyngitis, anaemia, cough, urinary tract infection and allergic 

reactions. Adverse reactions established for adult indications are considered applicable to preterm 

infants with ROP, though not all were observed in the RAINBOW trial. The long-term safety profile 

in preterm infants has not been established. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Cases of accidental overdose have been reported from the clinical studies in wet AMD and post-

marketing data. Adverse reactions associated with these reported cases were intraocular pressure 

increased, transient blindness, reduced visual acuity, corneal oedema, corneal pain, and eye pain. If an 

overdose occurs, intraocular pressure should be monitored and treated, if deemed necessary by the 

attending physician. 

 

 

  



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5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Ophthalmologicals, antineovascularisation agents, ATC code: S01LA04 

 

Mechanism of action 

 

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human 

vascular endothelial growth factor A (VEGF-A). It binds with high affinity to the VEGF-A isoforms 

(e.g. VEGF110, VEGF121 and VEGF165), thereby preventing binding of VEGF-A to its receptors 

VEGFR-1 and VEGFR-2. Binding of VEGF-A to its receptors leads to endothelial cell proliferation 

and neovascularisation, as well as vascular leakage, all of which are thought to contribute to the 

progression of the neovascular form of age-related macular degeneration, pathologic myopia and CNV 

or to visual impairment caused by either diabetic macular oedema or macular oedema secondary to 

RVO in adults and retinopathy of prematurity in preterm infants. 

 

Clinical efficacy and safety 

 

Treatment of wet AMD 

In wet AMD, the clinical safety and efficacy of Lucentis have been assessed in three randomised, 

double-masked, sham- or active-controlled studies of 24 months duration in patients with neovascular 

AMD. A total of 1,323 patients (879 active and 444 control) were enrolled in these studies. 

 

In study FVF2598g (MARINA), 716 patients with minimally classic or occult with no classic lesions 

were randomised in a 1:1:1 ratio to receive monthly injections of Lucentis 0.3 mg, Lucentis 0.5 mg or 

sham. 

 

In study FVF2587g (ANCHOR), 423 patients with predominantly classic CNV lesions were 

randomised in a 1:1:1 ratio to receive Lucentis 0.3 mg monthly, Lucentis 0.5 mg monthly or 

verteporfin PDT (at baseline and every 3 months thereafter if fluorescein angiography showed 

persistence or recurrence of vascular leakage). 

 

Key outcome measures are summarised in Table 1 and Figure 1. 

 

Table 1 Outcomes at Month 12 and Month 24 in study FVF2598g (MARINA) and FVF2587g 

(ANCHOR) 

 

  FVF2598g (MARINA) FVF2587g (ANCHOR) 

Outcome measure Month Sham 

(n=238) 

Lucentis 

0.5 mg 

(n=240) 

Verteporfin 

PDT (n=143) 

Lucentis 

0.5 mg 

(n=140) 

Loss of <15 letters in 

visual acuity (%)a 

(maintenance of 

vision, primary 

endpoint) 

Month 12 62% 95% 64% 96% 

Month 24 53% 90% 66% 90% 

Gain of ≥15 letters in 

visual acuity (%)a 

Month 12 5% 34% 6% 40% 

Month 24 4% 33% 6% 41% 

Mean change in 

visual acuity (letters) 

(SD)a 

Month 12 -10.5 (16.6) +7.2 (14.4) -9.5 (16.4) +11.3 (14.6) 

Month 24 -14.9 (18.7) +6.6 (16.5) -9.8 (17.6) +10.7 (16.5) 

a p<0.01      

 



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Figure 1 Mean change in visual acuity from baseline to Month 24 in study FVF2598g 

(MARINA) and study FVF2587g (ANCHOR) 

 

 
 

Results from both trials indicated that continued ranibizumab treatment may also be of benefit in 

patients who lost ≥15 letters of best-corrected visual acuity (BCVA) in the first year of treatment. 

 

Statistically significant patient-reported visual functioning benefits were observed in both MARINA 

and ANCHOR with ranibizumab treatment over the control group as measured by the NEI VFQ-25. 

 

In study FVF3192g (PIER), 184 patients with all forms of neovascular AMD were randomised in a 

1:1:1 ratio to receive Lucentis 0.3 mg, Lucentis 0.5 mg or sham injections once a month for 

3 consecutive doses, followed by a dose administered once every 3 months. From Month 14 of the 

study, sham-treated patients were allowed to receive ranibizumab and from Month 19, more frequent 

treatments were possible. Patients treated with Lucentis in PIER received a mean of 10 total 

treatments. 

 



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After an initial increase in visual acuity (following monthly dosing), on average, patients’ visual acuity 

declined with quarterly dosing, returning to baseline at Month 12 and this effect was maintained in 

most ranibizumab-treated patients (82%) at Month 24. Limited data from sham subjects who later 

received ranibizumab suggested that early initiation of treatment may be associated with better 

preservation of visual acuity. 

 

Data from two studies (MONT BLANC, BPD952A2308 and DENALI, BPD952A2309) conducted 

post approval confirmed the efficacy of Lucentis but did not demonstrate additional effect of the 

combined administration of verteporfin (Visudyne PDT) and Lucentis compared to Lucentis 

monotherapy. 

 

Treatment of visual impairment due to CNV secondary to PM 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to CNV in PM have 

been assessed based on the 12-month data of the double-masked, controlled pivotal study F2301 

(RADIANCE). In this study 277 patients were randomised in a 2:2:1 ratio to the following arms: 

 Group I (ranibizumab 0.5 mg, dosing regimen driven by “stability” criteria defined as no change 
in BCVA compared to two preceding monthly evaluations). 

 Group II (ranibizumab 0.5 mg, dosing regimen driven by “disease activity” criteria defined as 
vision impairment attributable to intra- or subretinal fluid or active leakage due to the CNV 

lesion as assessed by optical coherence tomography and/or fluorescence angiography). 

 Group III (vPDT - patients were allowed to receive ranibizumab treatment as of Month 3). 
In Group II, which is the recommended posology (see section 4.2), 50.9% of patients required 1 or 

2 injections, 34.5% required 3 to 5 injections and 14.7% required 6 to 12 injections over the 12-month 

study period. 62.9% of Group II patients did not require injections in the second 6 months of the study. 

 

The key outcomes from RADIANCE are summarised in Table 2 and Figure 2. 

 
Table 2 Outcomes at Month 3 and 12 (RADIANCE) 

 

 Group I 

Ranibizumab 

0.5 mg 

“vision stability” 

(n=105) 

Group II 

Ranibizumab 

0.5 mg 

“disease activity” 

(n=116) 

Group III 

vPDTb 

 

 

(n=55) 

Month 3    

Mean average BCVA change from Month 1 

to Month 3 compared to baselinea (letters) 

+10.5 +10.6 +2.2 

Proportion of patients who gained: 

≥15 letters, or reached ≥84 letters in BCVA 

 

38.1% 

 

43.1% 

 

14.5% 

Month 12    

Number of injections up to Month 12: 

Mean 

Median 

 

4.6 

4.0 

 

3.5 

2.5 

 

N/A 

N/A 

Mean average BCVA change from Month 1 

to Month 12 compared to baseline (letters) 

+12.8 +12.5 N/A 

Proportion of patients who gained: 

≥15 letters, or reached ≥84 letters in BCVA 

 

53.3% 

 

51.7% 

 

N/A 
a p<0.00001 comparison with vPDT control 
b Comparative control up to Month 3. Patients randomised to vPDT were allowed to receive 

ranibizumab treatment as of Month 3 (in Group III, 38 patients received ranibizumab as of Month 3) 

 



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Figure 2 Mean change from baseline BCVA over time to Month 12 (RADIANCE) 

 

 
 

The improvement of vision was accompanied by a reduction in central retinal thickness. 
 

Patient-reported benefits were observed with ranibizumab treatment arms over vPDT (p-value <0.05) 

in terms of improvement in the composite score and several subscales (general vision, near activities, 

mental health and dependency) of the NEI VFQ-25. 

 

Treatment of visual impairment due to CNV (other than secondary to PM and wet AMD) 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to CNV have been 

assessed based on the 12-month data of the double-masked, sham-controlled pivotal study G2301 

(MINERVA). In this study 178 adult patients were randomised in a 2:1 ratio to receive: 

 ranibizumab 0.5 mg at baseline, followed by an individualised dosing regimen driven by disease 
activity as assessed by visual acuity and/or anatomical parameters (e.g. VA impairment, 

intra/sub-retinal fluid, haemorrhage or leakage); 

 sham injection at baseline, followed by an individualised treatment regimen driven by disease 
activity. 

At Month 2, all patients received open-label treatment with ranibizumab as needed. 

 

Key outcome measures from MINERVA are summarised in Table 3 and Figure 3. An improvement of 

vision was observed and was accompanied by a reduction in central subfield thickness over the 

12-month period. 

 



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The mean number of injections given over 12 months was 5.8 in the ranibizumab arm versus 5.4 in 

those patients in the sham arm who were eligible to receive ranibizumab from Month 2 onwards. In 

the sham arm 7 out of 59 patients did not receive any treatment with ranibizumab in the study eye 

during the 12-month period. 

 

Table 3 Outcomes at Month 2 (MINERVA) 

 

 Ranibizumab 

0.5 mg (n=119) 

Sham (n=59) 

Mean BCVA change from baseline to Month 2 a  9.5 letters -0.4 letters 

Patients gaining ≥15 letters from baseline or reaching 

84 letters at Month 2 

31.4% 12.3% 

Patients not losing >15 letters from baseline at 

Month 2 

99.2% 94.7% 

Reduction in CSFTb from baseline to Month 2 a 77 µm -9.8 µm 
a One-sided p<0.001 comparison with sham control 
b CSFT - central retinal subfield thickness 

 

Figure 3 Mean change from baseline BCVA over time to Month 12 (MINERVA) 

 

 
 



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When comparing ranibizumab versus sham control at Month 2, a consistent treatment effect both 

overall and across baseline aetiology subgroups was observed: 

 

Table 4 Treatment effect overall and across baseline aetiology subgroups 
 

Overall and per baseline aetiology Treatment effect over 

sham [letters] 

Patient numbers [n] 

(treatment +sham) 

Overall 9.9 178 

Angioid streaks 14.6 27 

Post-inflammatory retinochoroidopathy 6.5 28 

Central serous chorioretinopathy 5.0 23 

Idiopathic chorioretinopathy 11.4 63 

Miscellaneous aetiologiesa 10.6 37 
a encompasses different aetiologies of low frequency of occurrence not included in the other subgroups 

 

In the pivotal study G2301 (MINERVA), five adolescent patients aged 12 to 17 years with visual 

impairment secondary to CNV received open-label treatment with ranibizumab 0.5 mg at baseline 

followed by an individualised treatment regimen as for the adult population. BCVA improved from 

baseline to Month 12 in all five patients, ranging from 5 to 38 letters (mean of 16.6 letters). The 

improvement of vision was accompanied by a stabilisation or reduction in central subfield thickness 

over the 12-month period. The mean number of ranibizumab injections given in the study eye over 

12 months was 3 (ranged from 2 to 5). Overall, ranibizumab treatment was well tolerated. 

 

Treatment of visual impairment due to DME 

The efficacy and safety of Lucentis have been assessed in three randomised, controlled studies of at 

least 12 months duration. A total of 868 patients (708 active and 160 control) were enrolled in these 

studies. 

 

In the phase II study D2201 (RESOLVE), 151 patients were treated with ranibizumab (6 mg/ml, n=51, 

10 mg/ml, n=51) or sham (n=49) by monthly intravitreal injections. The mean average change in 

BCVA from Month 1 to Month 12 compared to baseline was +7.8 (±7.72) letters in the pooled 

ranibizumab-treated patients (n=102), compared to -0.1 (±9.77) letters for sham-treated patients; and 

the mean change in BCVA at Month 12 from baseline was 10.3 (±9.1) letters compared to -1.4 (±14.2) 

letters, respectively (p<0.0001 for the treatment difference). 

 

In the phase III study D2301 (RESTORE), 345 patients were randomised in a 1:1:1 ratio to receive 

ranibizumab 0.5 mg monotherapy and sham laser photocoagulation, combined ranibizumab 0.5 mg 

and laser photocoagulation or sham injection and laser photocoagulation. 240 patients, who had 

previously completed the 12-month RESTORE study, were enrolled in the open-label, multicentre 

24-month extension (RESTORE Extension) study. Patients were treated with ranibizumab 0.5 mg pro 

re nata (PRN) in the same eye as the core study (D2301 RESTORE). 

 



16 

Key outcome measures are summarised in Table 5 (RESTORE and Extension) and Figure 4 

(RESTORE). 

 

Figure 4 Mean change in visual acuity from baseline over time in study D2301 (RESTORE) 

 

 
BL=baseline; SE=standard error of mean 

* Difference in least square means, p0.0001/0.0004 based on two-sided stratified Cochran-Mantel-

Haenszel test 

 

The effect at 12 months was consistent in most subgroups. However, subjects with a baseline BCVA 

>73 letters and macular oedema with central retinal thickness <300 µm did not appear to benefit from 

treatment with ranibizumab compared to laser photocoagulation. 

 



17 

Table 5 Outcomes at Month 12 in study D2301 (RESTORE) and at Month 36 in study 

D2301-E1 (RESTORE Extension) 

 

Outcome measures at Month 12 compared 

to baseline in study D2301 (RESTORE) 

Ranibizumab 

0.5 mg 

n=115 

Ranibizumab 

0.5 mg + Laser 

n=118 

Laser 

 

n=110 

Mean average change in BCVA from 

Month 1 to Month 12a (SD) 

6.1 (6.4)a 5.9 (7.9)a 0.8 (8.6) 

Mean change in BCVA at Month 12 

(SD) 

6.8 (8.3)a 6.4 (11.8)a 0.9 (11.4) 

Gain of ≥15 letters or BCVA ≥84 letters at 

Month 12 (%) 

22.6 22.9 8.2 

Mean number of injections (Months 0-11) 7.0  6.8 7.3 (sham) 

 

Outcome measure at Month 36 compared 

to D2301 (RESTORE) baseline in study 

D2301-E1 (RESTORE Extension) 

Prior ranibizumab 

0.5 mg 

n=83 

Prior ranibizumab 

0.5 mg + laser 

n=83 

Prior laser 

 

n=74 

Mean change in BCVA at Month 24 (SD) 7.9 (9.0) 6.7 (7.9) 5.4 (9.0) 

Mean change in BCVA at Month 36 (SD) 8.0 (10.1) 6.7 (9.6) 6.0 (9.4) 

Gain of ≥15 letters or BCVA ≥84 letters at 

Month 36 (%) 
27.7 30.1 21.6 

Mean number of injections 

(Months 12-35)* 
6.8 6.0 6.5 

ap<0.0001 for comparisons of ranibizumab arms vs. laser arm. 

n in D2301-E1 (RESTORE Extension) is the number of patients with a value at both D2301 

(RESTORE) baseline (Month 0) and at the Month 36 visit. 

* The proportion of patients who did not require any ranibizumab treatment during the extension 

phase was 19%, 25% and 20% in the prior ranibizumab, prior ranibizumab + laser and prior laser 

groups, respectively. 

 

Statistically significant patient-reported benefits for most vision-related functions were observed with 

ranibizumab (with or without laser) treatment over the control group as measured by the NEI VFQ-25. 

For other subscales of this questionnaire no treatment differences could be established. 

 

The long-term safety profile of ranibizumab observed in the 24-month extension study is consistent 

with the known Lucentis safety profile. 

 

In the phase IIIb study D2304 (RETAIN), 372 patients were randomised in 1:1:1 ratio to receive: 

 ranibizumab 0.5 mg with concomitant laser photocoagulation on a treat-and-extend (TE) 
regimen, 

 ranibizumab 0.5 mg monotherapy on a TE regimen, 

 ranibizumab 0.5 mg monotherapy on a PRN regimen. 
 

In all groups, ranibizumab was administered monthly until BCVA was stable for at least three 

consecutive monthly assessments. On TE, ranibizumab was administered at treatment intervals of 

2-3 months. In all groups, monthly treatment was re-initiated upon a decrease in BCVA due to DME 

progression and continued until stable BCVA was reached again. 

 

The number of scheduled treatment visits after the initial 3 injections, was 13 and 20 for the TE and 

PRN regimens, respectively. With both TE regimens, more than 70% of patients maintained their 

BCVA with an average visit frequency of ≥2 months. 

 



18 

The key outcome measures are summarised in Table 6. 

 

Table 6 Outcomes in study D2304 (RETAIN) 

 

Outcome measure 

compared to baseline 

TE ranibizumab 

0.5 mg + laser 

n=117 

TE ranibizumab 

0.5 mg alone 

n=125 

PRN ranibizumab 

0.5 mg 

n=117 

Mean average change 

in BCVA from 

Month 1 to Month 12 

(SD) 

5.9 (5.5) a 6.1 (5.7) a 6.2 (6.0) 

Mean average change 

in BCVA from 

Month 1 to Month 24 

(SD) 

6.8 (6.0) 6.6 (7.1) 7.0 (6.4) 

Mean change in BCVA 

at Month 24 (SD) 
8.3 (8.1) 6.5 (10.9) 8.1 (8.5) 

Gain of ≥15 letters or 

BCVA ≥84 letters at 

Month 24(%) 

25.6 28.0 30.8 

Mean number of 

injections 

(months 0-23) 

12.4 12.8 10.7 

ap<0.0001 for assessment of non-inferiority to PRN 

 

In DME studies, the improvement in BCVA was accompanied by a reduction over time in mean CSFT 

in all the treatment groups. 

 

Treatment of PDR 

The clinical safety and efficacy of Lucentis in patients with PDR have been assessed in Protocol S 

which evaluated the treatment with ranibizumab 0.5 mg intravitreal injections compared with 

panretinal photocoagulation (PRP). The primary endpoint was the mean visual acuity change at year 2. 

Additionally, change in diabetic retinopathy (DR) severity was assessed based on fundus photographs 

using the DR severity score (DRSS). 

 

Protocol S was a multicentre, randomised, active-controlled, parallel-assignment, non-inferiority 

phase III study in which 305 patients (394 study eyes) with PDR with or without DME at baseline 

were enrolled. The study compared ranibizumab 0.5 mg intravitreal injections to standard treatment 

with PRP. A total of 191 eyes (48.5%) were randomised to ranibizumab 0.5 mg and 203 eyes (51.5%) 

eyes were randomised to PRP. A total of 88 eyes (22.3%) had baseline DME: 42 (22.0%) and 

46 (22.7%) eyes in the ranibizumab and PRP groups, respectively. 

 

In this study, the mean visual acuity change at year 2 was +2.7 letters in the ranibizumab group 

compared to -0.7 letters in the PRP group. The difference in least square means was 3.5 letters (95% 

CI: [0.2 to 6.7]). 

 
At year 1, 41.8% of eyes experienced a ≥2-step improvement in the DRSS when treated with 

ranibizumab (n=189) compared to 14.6% of eyes treated with PRP (n=199). The estimated difference 

between ranibizumab and laser was 27.4% (95% CI: [18.9, 35.9]). 

 



19 

Table 7 DRSS improvement or worsening of ≥2 or ≥3 steps at year 1 in Protocol S (LOCF 

Method) 

Categorised change 

from baseline 

Protocol S 

Ranibizumab 

0.5 mg 

(N=189) 

PRP 

(N=199) 

Difference in 

proportion (%), CI 

≥2-step improvement 

n (%) 79 

(41.8%) 

29 

(14.6%) 

27.4 

(18.9, 35.9) 

≥3-step improvement 

n (%) 54 

(28.6%) 

6 

(3.0%) 

25.7 

(18.9, 32.6) 

≥2-step worsening 

n (%) 3 

(1.6%) 

23 

(11.6%) 

-9.9 

(-14.7, -5.2) 

≥3-step worsening 

n (%) 1 

(0.5%) 

8 

(4.0%) 

-3.4 

(-6.3, -0.5) 

DRSS = diabetic retinopathy severity score, n = number of patients who satisfied the condition at the 

visit, N = total number of study eyes. 

 

At year 1 in the ranibizumab-treated group in Protocol S, ≥2-step improvement in DRSS was 

consistent in eyes without DME (39.9%) and with baseline DME (48.8%). 

 

An analysis of year 2 data from Protocol S demonstrated that 42.3% (n=80) of eyes in the 

ranibizumab-treated group had ≥2-step improvement in DRSS from baseline compared with 23.1% 

(n=46) of eyes in the PRP group. In the ranibizumab-treated group, ≥2-step improvement in DRSS 

from baseline was observed in 58.5% (n=24) of eyes with baseline DME and 37.8% (n=56) of eyes 

without DME. 

 

DRSS was also assessed in three separate active-controlled phase III DME studies (ranibizumab 

0.5 mg PRN vs laser) that included a total of 875 patients, of whom approximately 75% were of Asian 

origin. In a meta-analysis of these studies, 48.4% of the 315 patients with gradable DRSS scores in the 

subgroup of patients with moderately severe non-proliferative DR (NPDR) or worse at baseline 

experienced a ≥2-step improvement in the DRSS at Month 12 when treated with ranibizumab (n=192) 

vs 14.6% of patients treated with laser (n=123). The estimated difference between ranibizumab and 

laser was 29.9% (95% CI: [20.0, 39.7]). In the 405 DRSS gradable patients with moderate NPDR or 

better, a ≥2-step DRSS improvement was observed in 1.4% and 0.9% of the ranibizumab and laser 

groups, respectively. 

 

Treatment of visual impairment due to macular oedema secondary to RVO 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to macular oedema 

secondary to RVO have been assessed in the randomised, double-masked, controlled studies BRAVO 

and CRUISE that recruited subjects with BRVO (n=397) and CRVO (n=392), respectively. In both 

studies, subjects received either 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, 

patients in the sham-control arms switched to 0.5 mg ranibizumab. 

 



20 

Key outcome measures from BRAVO and CRUISE are summarised in Table 8 and Figures 5 and 6. 

 

Table 8 Outcomes at Month 6 and 12 (BRAVO and CRUISE) 

 

 BRAVO CRUISE 

 Sham/Lucentis 

0.5 mg 

(n=132) 

Lucentis 

0.5 mg 

(n=131) 

Sham/Lucentis 

0.5 mg 

(n=130) 

Lucentis 

0.5 mg 

(n=130) 

Mean change in visual acuity 

at Month 6a (letters) (SD) 

(primary endpoint) 

7.3 (13.0) 18.3 (13.2) 0.8 (16.2) 14.9 (13.2) 

Mean change in BCVA at 

Month 12 (letters) (SD) 

12.1 (14.4) 18.3 (14.6) 7.3 (15.9) 13.9 (14.2) 

Gain of ≥15 letters in visual 

acuity at Month 6a (%) 

28.8 61.1 16.9 47.7 

Gain of ≥15 letters in visual 

acuity at Month 12 (%) 

43.9 60.3 33.1 50.8 

Proportion (%) receiving 

laser rescue over 12 months 

61.4 34.4 NA NA 

ap<0.0001for both studies 

 

Figure 5 Mean change from baseline BCVA over time to Month 6 and Month 12 (BRAVO) 

 

 



21 

Figure 6 Mean change from baseline BCVA over time to Month 6 and Month 12 (CRUISE) 

 

 
In both studies, the improvement of vision was accompanied by a continuous and significant reduction 

in the macular oedema as measured by central retinal thickness. 

 

In patients with CRVO (CRUISE and extension study HORIZON): Subjects treated with sham in the 

first 6 months who subsequently received ranibizumab did not achieve comparable gains in VA by 

Month 24 (~6 letters) compared to subjects treated with ranibizumab from study start (~12 letters). 

 

Statistically significant patient-reported benefits in subscales related to near and distance activity were 

observed with ranibizumab treatment over the control group as measured by the NEI VFQ-25. 

 

The long-term (24 months) clinical safety and efficacy of Lucentis in patients with visual impairment 

due to macular oedema secondary to RVO were assessed in the BRIGHTER (BRVO) and CRYSTAL 

(CRVO) studies. In both studies, subjects received a 0.5 mg ranibizumab PRN dosing regimen driven 

by individualised stabilisation criteria. BRIGHTER was a 3-arm randomised active-controlled study 

that compared 0.5 mg ranibizumab given as monotherapy or in combination with adjunctive laser 

photocoagulation to laser photocoagulation alone. After 6 months, subjects in the laser arm could 

receive 0.5 mg ranibizumab. CRYSTAL was a single-arm study with 0.5 mg ranibizumab 

monotherapy. 

 



22 

Key outcome measures from BRIGHTER and CRYSTAL are shown in Table 9. 

 

Table 9 Outcomes at Months 6 and 24 (BRIGHTER and CRYSTAL) 

 

 BRIGHTER CRYSTAL 
 Lucentis 0.5 mg 

N=180 
Lucentis 0.5 mg 

+ Laser 

N=178 

Laser* 

N=90 
Lucentis 0.5 mg 

N=356 

Mean change in 

BCVA at 

Month 6a (letters) 

(SD) 

+14.8 

(10.7) 
+14.8 

(11.13) 
+6.0 

(14.27) 
+12.0 

(13.95) 

Mean change in 

BCVA at 

Month 24b 

(letters) (SD) 

+15.5 

(13.91) 
+17.3 

(12.61) 
+11.6 

(16.09) 
+12.1 

(18.60) 

Gain of 

≥15 letters in 

BCVA at 

Month 24 (%) 

52.8 59.6 43.3 49.2 

Mean number of 

injections (SD) 

(Months 0-23) 

11.4 

(5.81) 
11.3 (6.02) NA 13.1 (6.39) 

a p<0.0001for both comparisons in BRIGHTER at Month 6: Lucentis 0.5 mg vs Laser and 

Lucentis 0.5 mg + Laser vs Laser. 
b p<0.0001for null hypothesis in CRYSTAL that the mean change at Month 24 from baseline 

is zero. 

* Starting at Month 6 ranibizumab 0.5 mg treatment was allowed (24 patients were treated with 

laser only). 

 

In BRIGHTER, ranibizumab 0.5 mg with adjunctive laser therapy demonstrated non-inferiority versus 

ranibizumab monotherapy from baseline to Month 24 (95% CI -2.8, 1.4). 

 

In both studies, a rapid and statistically significant decrease from baseline in central retinal subfield 

thickness was observed at Month 1. This effect was maintained up to Month 24. 

 

The effect of ranibizumab treatment was similar irrespective of the presence of retinal ischaemia. In 

BRIGHTER, patients with ischaemia present (N=46) or absent (N=133) and treated with ranibizumab 

monotherapy had a mean change from baseline of +15.3 and +15.6 letters, respectively, at Month 24. 

In CRYSTAL, patients with ischaemia present (N=53) or absent (N=300) and treated with 

ranibizumab monotherapy had a mean change from baseline of +15.0 and +11.5 letters, respectively. 

 

The effect in terms of visual improvement was observed in all patients treated with 0.5 mg 

ranibizumab monotherapy regardless of their disease duration in both BRIGHTER and CRYSTAL. In 

patients with <3 months disease duration an increase in visual acuity of 13.3 and 10.0 letters was seen 

at Month 1; and 17.7 and 13.2 letters at Month 24 in BRIGHTER and CRYSTAL, respectively. The 

corresponding visual acuity gain in patients with ≥12 months disease duration was 8.6 and 8.4 letters 

in the respective studies. Treatment initiation at the time of diagnosis should be considered. 

 

The long-term safety profile of ranibizumab observed in the 24-month studies is consistent with the 

known Lucentis safety profile. 

 



23 

Paediatric population 

 

Treatment of ROP in preterm infants 

The clinical safety and efficacy of Lucentis 0.2 mg for the treatment of ROP in preterm infants have 

been assessed based on the 6-month data of the randomised, open-label, 3-arm, parallel-group 

superiority study H2301 (RAINBOW), which was designed to evaluate ranibizumab 0.2 mg and 

0.1 mg given as intravitreal injections in comparison to laser therapy. Eligible patients had one of the 

following retinal findings in each eye: 

 Zone I, stage 1+, 2+, 3 or 3+ disease, or 

 Zone II, stage 3+ disease, or 

 Aggressive posterior (AP)-ROP 
 

In this study, 225 patients were randomised in a 1:1:1 ratio to receive intravitreal ranibizumab 0.2 mg 

(n=74), 0.1 mg (n=77), or laser therapy (n=74). 

 

Treatment success, as measured by the absence of active ROP and absence of unfavourable structural 

outcomes in both eyes 24 weeks after the first study treatment, was highest with ranibizumab 0.2 mg 

(80%) compared to laser therapy (66.2%) (see Table 10). The majority of patients treated with 

ranibizumab 0.2 mg (78.1%) received a single injection per eye. 

 

Table 10 Outcomes at Week 24 (RAINBOW) 

 

 Treatment success  

Treatment n/M (%) 95% CI Comparison Odds ratio 

(OR)a 

95% CI p-valueb 

Ranibizumab 

0.2 mg 

(N=74) 

56/70 

(80.0) 

(0.6873, 

0.8861) 

Ranibizumab 

0.2 mg vs 

laser 

2.19 (0.9932, 

4.8235) 

0.0254 

Laser therapy 

(N=74) 

45/68 

(66.2) 

(0.5368, 

0.7721) 

    

CI = confidence interval, M = total number of patients with non-missing value on primary efficacy 

outcome (including imputed values), n = number of patients with absence of active ROP and 

absence of unfavourable structural outcome in both eyes 24 weeks after the first study treatment 

(including imputed values). 

If a patient died or switched study treatment before or at week 24, then the patient was considered 

as having active ROP and unfavourable structural outcomes at week 24. 
a Odds ratio is calculated by using Cochran-Mantel-Haenszel test with ROP zone at baseline 

(zone I and II; per CRF) as stratum factor. 
b p-value for pairwise comparison is one-sided. For the primary endpoint the pre-specified 

significance level for the one-sided p-value was 0.025. 

 
During the 24 weeks of the study, fewer patients in the ranibizumab 0.2 mg group switched to another 

treatment modality due to lack of response compared with the laser group (14.9% vs. 24.3%). 

Unfavourable structural outcomes were less frequently reported for ranibizumab 0.2 mg (1 patient, 

1.4%) compared with laser therapy (7 patients, 10.1%). 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Lucentis in all subsets of the paediatric population in neovascular AMD, visual impairment due to 

DME, visual impairment due to macular oedema secondary to RVO, visual impairment due to CNV 

and diabetic retinopathy (see section 4.2 for information on paediatric use). In addition the European 

Medicines Agency has waived the obligation to submit the results of studies with Lucentis in the 

following subsets of the paediatric population for ROP: term newborn infants, infants, children and 

adolescents. 

 



24 

5.2 Pharmacokinetic properties 
 

Following monthly intravitreal administration of Lucentis to patients with neovascular AMD, serum 

concentrations of ranibizumab were generally low, with maximum levels (Cmax) generally below the 

ranibizumab concentration necessary to inhibit the biological activity of VEGF by 50% (11-27 ng/ml, 

as assessed in an in vitro cellular proliferation assay). Cmax was dose proportional over the dose range 

of 0.05 to 1.0 mg/eye. Serum concentrations in a limited number of DME patients indicate that a 

slightly higher systemic exposure cannot be excluded compared to those observed in neovascular 

AMD patients. Serum ranibizumab concentrations in RVO patients were similar or slightly higher 

compared to those observed in neovascular AMD patients. 

 

Based on analysis of population pharmacokinetics and disappearance of ranibizumab from serum for 

patients with neovascular AMD treated with the 0.5 mg dose, the average vitreous elimination half-life 

of ranibizumab is approximately 9 days. Upon monthly intravitreal administration of Lucentis 

0.5 mg/eye, serum ranibizumab Cmax, attained approximately 1 day after dosing, is predicted to 

generally range between 0.79 and 2.90 ng/ml, and Cmin is predicted to generally range between 0.07 

and 0.49 ng/ml. Serum ranibizumab concentrations are predicted to be approximately 90,000-fold 

lower than vitreal ranibizumab concentrations. 

 

Patients with renal impairment: No formal studies have been conducted to examine the 

pharmacokinetics of Lucentis in patients with renal impairment. In a population pharmacokinetic 

analysis of neovascular AMD patients, 68% (136 of 200) of patients had renal impairment (46.5% 

mild [50-80 ml/min], 20% moderate [30-50 ml/min], and 1.5% severe [<30 ml/min]). In RVO 

patients, 48.2% (253 of 525) had renal impairment (36.4% mild, 9.5% moderate and 2.3% severe). 

Systemic clearance was slightly lower, but this was not clinically significant. 

 

Hepatic impairment: No formal studies have been conducted to examine the pharmacokinetics of 

Lucentis in patients with hepatic impairment. 

 

Paediatric population 

 

Following intravitreal administration of Lucentis to preterm infants with ROP at a dose of 0.2 mg (per 

eye), serum ranibizumab concentrations were higher than those observed in neovascular AMD adult 

patients receiving 0.5 mg in one eye. Based on a population pharmacokinetic analysis, the differences 

in Cmax and AUCinf were approximately 16-fold and 12-fold higher, respectively. The apparent 

systemic half-life was approximately 6 days. A PK/PD analysis showed no clear relationship between 

systemic ranibizumab concentrations and systemic VEGF concentrations. 
 

5.3 Preclinical safety data 
 

Bilateral intravitreal administration of ranibizumab to cynomolgus monkeys at doses between 

0.25 mg/eye and 2.0 mg/eye once every 2 weeks for up to 26 weeks resulted in dose-dependent ocular 

effects. 

 

Intraocularly, there were dose-dependent increases in anterior chamber flare and cells with a peak 

2 days after injection. The severity of the inflammatory response generally diminished with 

subsequent injections or during recovery. In the posterior segment, there were vitreal cell infiltration 

and floaters, which also tended to be dose-dependent and generally persisted to the end of the 

treatment period. In the 26-week study, the severity of the vitreous inflammation increased with the 

number of injections. However, evidence of reversibility was observed after recovery. The nature and 

timing of the posterior segment inflammation is suggestive of an immune-mediated antibody response, 

which may be clinically irrelevant. Cataract formation was observed in some animals after a relatively 

long period of intense inflammation, suggesting that the lens changes were secondary to severe 

inflammation. A transient increase in post-dose intraocular pressure was observed following 

intravitreal injections, irrespective of dose. 

 



25 

Microscopic ocular changes were related to inflammation and did not indicate degenerative processes. 

Granulomatous inflammatory changes were noted in the optic disc of some eyes. These posterior 

segment changes diminished, and in some instances resolved, during the recovery period. 

 

Following intravitreal administration, no signs of systemic toxicity were detected. Serum and vitreous 

antibodies to ranibizumab were found in a subset of treated animals. 

 

No carcinogenicity or mutagenicity data are available. 

 

In pregnant monkeys, intravitreal ranibizumab treatment resulting in maximal systemic exposures 

0.9-7-fold a worst case clinical exposure did not elicit developmental toxicity or teratogenicity, and 

had no effect on weight or structure of the placenta, although, based on its pharmacological effect 

ranibizumab should be regarded as potentially teratogenic and embryo-/foetotoxic. 

 

The absence of ranibizumab-mediated effects on embryo-foetal development is plausibly related 

mainly to the inability of the Fab fragment to cross the placenta. Nevertheless, a case was described 

with high maternal ranibizumab serum levels and presence of ranibizumab in foetal serum, suggesting 

that the anti-ranibizumab antibody acted as (Fc region containing) carrier protein for ranibizumab, 

thereby decreasing its maternal serum clearance and enabling its placental transfer. As the embryo-

foetal development investigations were performed in healthy pregnant animals and disease (such as 

diabetes) may modify the permeability of the placenta towards a Fab fragment, the study should be 

interpreted with caution. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

α,α-trehalose dihydrate 

Histidine hydrochloride, monohydrate 

Histidine 

Polysorbate 20 

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 
 

3 years 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Keep the vial in the outer carton in order to protect from light. 

Prior to use, the unopened vial may be kept at room temperature (25°C) for up to 24 hours. 

 

6.5 Nature and contents of container 

 

Vial-only pack 

 

One vial (type I glass) with a stopper (chlorobutyl rubber) containing 0.23 ml sterile solution. 

 



26 

Vial + filter needle pack 

 

One vial (type I glass) with a stopper (chlorobutyl rubber) containing 0.23 ml sterile solution and 

1 blunt filter needle (18G x 1½″, 1.2 mm x 40 mm, 5 µm). 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 
 

Vial-only pack 

 

The vial is for single use only. After injection any unused product must be discarded. Any vial 

showing signs of damage or tampering must not be used. The sterility cannot be guaranteed unless the 

packaging seal remains intact. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G) 

- a 1 ml sterile syringe (including a 0.05 ml mark) and an injection needle (30G x ½″), for adult 

patients 

- a low volume high accuracy sterile syringe, provided together with an injection needle 

(30G x ½″) in the VISISURE kit, for preterm infants 

These medical devices are not included within this pack. 

 

Vial + filter needle pack 

 

The vial and filter needle are for single use only. Re-use may lead to infection or other illness/injury. 

All components are sterile. Any component with packaging showing signs of damage or tampering 

must not be used. The sterility cannot be guaranteed unless the component packaging seal remains 

intact. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, provided) 

- a 1 ml sterile syringe (including a 0.05 ml mark, not included within this pack) and an injection 

needle (30G x ½″, not included within this pack), for adult patients 

- a low volume high accuracy sterile syringe, provided together with an injection needle 

(30G x ½″) in the VISISURE kit (not included within this pack), for preterm infants 

 

To prepare Lucentis for intravitreal administration to adults, please adhere to the following 

instructions: 

 

1. Before withdrawal, the outer part of the rubber stopper of the vial should be disinfected. 

 

2. Assemble a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm) onto a 1 ml syringe using aseptic 

technique. Push the blunt filter needle into the centre of the vial stopper until the needle touches 

the bottom edge of the vial. 

 

3. Withdraw all the liquid from the vial, keeping the vial in an upright position, slightly inclined to 

ease complete withdrawal. 

 

4. Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to 

completely empty the filter needle. 

 

5. Leave the blunt filter needle in the vial and disconnect the syringe from the blunt filter needle. 

The filter needle should be discarded after withdrawal of the vial contents and should not be 

used for the intravitreal injection. 

 



27 

6. Aseptically and firmly assemble an injection needle (30G x ½″, 0.3 mm x 13 mm) onto the 

syringe. 

 

7. Carefully remove the cap from the injection needle without disconnecting the injection needle 

from the syringe. 

 

Note: Grip at the hub of the injection needle while removing the cap. 

 

8. Carefully expel the air along with the excess solution and adjust the dose to the 0.05 ml mark on 

the syringe. The syringe is ready for injection. 

 

Note: Do not wipe the injection needle. Do not pull back on the plunger. 

 

After injection, do not recap the needle or detach it from the syringe. Dispose of the used syringe 

together with the needle in a sharps disposal container or in accordance with local requirements. 

 

Use in the paediatric population 

 

To prepare Lucentis for intravitreal administration to preterm infants, please adhere to the 

instructions for use included in the VISISURE kit. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/374/002 

EU/1/06/374/004 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22 January 2007 

Date of latest renewal: 11 November 2016 

 

 

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 



28 

1. NAME OF THE MEDICINAL PRODUCT 
 

Lucentis 10 mg/ml solution for injection in pre-filled syringe 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One ml contains 10 mg ranibizumab*. One pre-filled syringe contains 0.165 ml, equivalent to 1.65 mg 

ranibizumab. The extractable volume of one pre-filled syringe is 0.1 ml. This provides a usable 

amount to deliver a single dose of 0.05 ml containing 0.5 mg ranibizumab. 

*Ranibizumab is a humanised monoclonal antibody fragment produced in Escherichia coli cells by 

recombinant DNA technology. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection. 

 

Clear, colourless to pale yellow aqueous solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Lucentis is indicated in adults for: 

 The treatment of neovascular (wet) age-related macular degeneration (AMD) 

 The treatment of visual impairment due to diabetic macular oedema (DME) 

 The treatment of proliferative diabetic retinopathy (PDR) 

 The treatment of visual impairment due to macular oedema secondary to retinal vein occlusion 
(branch RVO or central RVO) 

 The treatment of visual impairment due to choroidal neovascularisation (CNV) 
 

4.2 Posology and method of administration 

 

Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections. 

 

Posology 

 

The recommended dose for Lucentis is 0.5 mg given as a single intravitreal injection. This 

corresponds to an injection volume of 0.05 ml. The interval between two doses injected into the same 

eye should be at least four weeks. 

 

Treatment is initiated with one injection per month until maximum visual acuity is achieved and/or 

there are no signs of disease activity i.e. no change in visual acuity and in other signs and symptoms of 

the disease under continued treatment. In patients with wet AMD, DME, PDR and RVO, initially, 

three or more consecutive, monthly injections may be needed. 

 

Thereafter, monitoring and treatment intervals should be determined by the physician and should be 

based on disease activity, as assessed by visual acuity and/or anatomical parameters. 

 

If, in the physician’s opinion, visual and anatomic parameters indicate that the patient is not benefiting 

from continued treatment, Lucentis should be discontinued. 

 



29 

Monitoring for disease activity may include clinical examination, functional testing or imaging 

techniques (e.g. optical coherence tomography or fluorescein angiography). 

 

If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is 

achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise 

until signs of disease activity or visual impairment recur. The treatment interval should be extended by 

no more than two weeks at a time for wet AMD and may be extended by up to one month at a time for 

DME. For PDR and RVO, treatment intervals may also be gradually extended, however there are 

insufficient data to conclude on the length of these intervals. If disease activity recurs, the treatment 

interval should be shortened accordingly. 

 

The treatment of visual impairment due to CNV should be determined individually per patient based 

on disease activity. Some patients may only need one injection during the first 12 months; others may 

need more frequent treatment, including a monthly injection. For CNV secondary to pathologic 

myopia (PM), many patients may only need one or two injections during the first year (see 

section 5.1). 

 

Lucentis and laser photocoagulation in DME and in macular oedema secondary to BRVO 

There is some experience of Lucentis administered concomitantly with laser photocoagulation (see 

section 5.1). When given on the same day, Lucentis should be administered at least 30 minutes after 

laser photocoagulation. Lucentis can be administered in patients who have received previous laser 

photocoagulation. 

 

Lucentis and verteporfin photodynamic therapy in CNV secondary to PM 

There is no experience of concomitant administration of Lucentis and verteporfin. 

 

Special populations 

 

Hepatic impairment 

Lucentis has not been studied in patients with hepatic impairment. However, no special considerations 

are needed in this population. 

 

Renal impairment 

Dose adjustment is not needed in patients with renal impairment (see section 5.2). 

 

Elderly 

No dose adjustment is required in the elderly. There is limited experience in patients older than 

75 years with DME. 

 

Paediatric population 

The safety and efficacy of Lucentis in children and adolescents below 18 years of age have not been 

established. Available data in adolescent patients aged 12 to 17 years with visual impairment due to 

CNV are described in section 5.1. 

 

Method of administration 

 

Single-use pre-filled syringe for intravitreal use only. The pre-filled syringe contains more than the 

recommended dose of 0.5 mg. The extractable volume of the pre-filled syringe (0.1 ml) is not to be 

used in total. The excess volume should be expelled prior to injection. Injecting the entire volume of 

the pre-filled syringe could result in overdose. To expel the air bubble along with the excess medicinal 

product, slowly push the plunger until the edge below the dome of the rubber stopper is aligned with 

the black dosing line on the syringe (equivalent to 0.05 ml, i.e., 0.5 mg ranibizumab). 

 

Lucentis should be inspected visually for particulate matter and discoloration prior to administration. 

 



30 

The injection procedure should be carried out under aseptic conditions, which includes the use of 

surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent) 

and the availability of sterile paracentesis (if required). The patient’s medical history for 

hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure 

(see section 4.4). Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the 

periocular skin, eyelid and ocular surface should be administered prior to the injection, in accordance 

with local practice. 

 

For information on preparation of Lucentis, see section 6.6. 

 

The injection needle should be inserted 3.5-4.0 mm posterior to the limbus into the vitreous cavity, 

avoiding the horizontal meridian and aiming towards the centre of the globe. The injection volume of 

0.05 ml is then delivered; a different scleral site should be used for subsequent injections. Each pre-

filled syringe should only be used for the treatment of a single eye. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Patients with active or suspected ocular or periocular infections. 

 

Patients with active severe intraocular inflammation. 

 

4.4 Special warnings and precautions for use 
 

Intravitreal injection-related reactions 

 

Intravitreous injections, including those with Lucentis, have been associated with endophthalmitis, 

intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic 

cataract (see section 4.8). Proper aseptic injection techniques must always be used when administering 

Lucentis. In addition, patients should be monitored during the week following the injection to permit 

early treatment if an infection occurs. Patients should be instructed to report any symptoms suggestive 

of endophthalmitis or any of the above mentioned events without delay. 

 

Intraocular pressure increases 

 

Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of injection of 

Lucentis. Sustained IOP increases have also been identified (see section 4.8). Both intraocular pressure 

and the perfusion of the optic nerve head must be monitored and managed appropriately. 

 

Patients should be informed of the symptoms of these potential adverse reactions and instructed to 

inform their physician if they develop signs such as eye pain or increased discomfort, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in their vision, or 

increased sensitivity to light (see section 4.8). 

 

Bilateral treatment 

 

Limited data on bilateral use of Lucentis (including same-day administration) do not suggest an 

increased risk of systemic adverse events compared with unilateral treatment. 

 

Immunogenicity 

 

There is a potential for immunogenicity with Lucentis. Since there is a potential for an increased 

systemic exposure in subjects with DME, an increased risk for developing hypersensitivity in this 

patient population cannot be excluded. Patients should also be instructed to report if an intraocular 

inflammation increases in severity, which may be a clinical sign attributable to intraocular antibody 

formation. 



31 

 

Concomitant use of other anti-VEGF (vascular endothelial growth factor) 

 

Lucentis should not be administered concurrently with other anti-VEGF medicinal products (systemic 

or ocular). 

 

Withholding Lucentis 

 

The dose should be withheld and treatment should not be resumed earlier than the next scheduled 

treatment in the event of: 

 a decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared with the last 
assessment of visual acuity; 

 an intraocular pressure of ≥30 mmHg; 

 a retinal break; 

 a subretinal haemorrhage involving the centre of the fovea, or, if the size of the haemorrhage is 
≥50%, of the total lesion area; 

 performed or planned intraocular surgery within the previous or next 28 days. 
 

Retinal pigment epithelial tear 

 

Risk factors associated with the development of a retinal pigment epithelial tear after anti-VEGF 

therapy for wet AMD and potentially also other forms of CNV, include a large and/or high pigment 

epithelial retinal detachment. When initiating ranibizumab therapy, caution should be used in patients 

with these risk factors for retinal pigment epithelial tears. 

 

Rhegmatogenous retinal detachment or macular holes 

 

Treatment should be discontinued in subjects with rhegmatogenous retinal detachment or stage 3 or 4 

macular holes. 

 

Populations with limited data 

 

There is only limited experience in the treatment of subjects with DME due to type I diabetes. 

Lucentis has not been studied in patients who have previously received intravitreal injections, in 

patients with active systemic infections, or in patients with concurrent eye conditions such as retinal 

detachment or macular hole. There is limited experience of treatment with Lucentis in diabetic patients 

with an HbA1c over 108 mmol/mol (12%) and no experience in patients with uncontrolled 

hypertension. This lack of information should be considered by the physician when treating such 

patients. 

 

There are insufficient data to conclude on the effect of Lucentis in patients with RVO presenting 

irreversible ischaemic visual function loss. 

 

In patients with PM, there are limited data on the effect of Lucentis in patients who have previously 

undergone unsuccessful verteporfin photodynamic therapy (vPDT) treatment. Also, while a consistent 

effect was observed in subjects with subfoveal and juxtafoveal lesions, there are insufficient data to 

conclude on the effect of Lucentis in PM subjects with extrafoveal lesions. 

 

Systemic effects following intravitreal use 

 

Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have 

been reported following intravitreal injection of VEGF inhibitors. 

 

There are limited data on safety in the treatment of DME, macular oedema due to RVO and CNV 

secondary to PM patients with prior history of stroke or transient ischaemic attacks. Caution should be 

exercised when treating such patients (see section 4.8). 
 



32 

4.5 Interaction with other medicinal products and other forms of interaction 
 

No formal interaction studies have been performed. 

 

For the adjunctive use of verteporfin photodynamic therapy (PDT) and Lucentis in wet AMD and PM, 

see section 5.1. 

 

For the adjunctive use of laser photocoagulation and Lucentis in DME and BRVO, see sections 4.2 

and 5.1. 

 

In clinical studies for the treatment of visual impairment due to DME, the outcome with regard to 

visual acuity or central retinal subfield thickness (CSFT) in patients treated with Lucentis was not 

affected by concomitant treatment with thiazolidinediones. 

 

4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential/contraception in females 

 

Women of childbearing potential should use effective contraception during treatment. 

 

Pregnancy 

 

For ranibizumab no clinical data on exposed pregnancies are available. Studies in cynomolgus 

monkeys do not indicate direct or indirect harmful effects with respect to pregnancy or 

embryonal/foetal development (see section 5.3). The systemic exposure to ranibizumab is low after 

ocular administration, but due to its mechanism of action, ranibizumab must be regarded as potentially 

teratogenic and embryo-/foetotoxic. Therefore, ranibizumab should not be used during pregnancy 

unless the expected benefit outweighs the potential risk to the foetus. For women who wish to become 

pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the 

last dose of ranibizumab before conceiving a child. 

 

Breast-feeding 

 

It is unknown whether Lucentis is excreted in human milk. Breast-feeding is not recommended during 

the use of Lucentis. 

 

Fertility 

 

There are no data available on fertility. 

 

4.7 Effects on ability to drive and use machines 
 

The treatment procedure may induce temporary visual disturbances, which may affect the ability to 

drive or use machines (see section 4.8). Patients who experience these signs must not drive or use 

machines until these temporary visual disturbances subside. 

 

  



33 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The majority of adverse reactions reported following administration of Lucentis are related to the 

intravitreal injection procedure. 

 

The most frequently reported ocular adverse reactions following injection of Lucentis are: eye pain, 

ocular hyperaemia, increased intraocular pressure, vitritis, vitreous detachment, retinal haemorrhage, 

visual disturbance, vitreous floaters, conjunctival haemorrhage, eye irritation, foreign body sensation 

in eyes, increased lacrimation, blepharitis, dry eye and eye pruritus. 

 

The most frequently reported non-ocular adverse reactions are headache, nasopharyngitis and 

arthralgia. 

 

Less frequently reported, but more serious, adverse reactions include endophthalmitis, blindness, 
retinal detachment, retinal tear and iatrogenic traumatic cataract (see section 4.4). 

 

The adverse reactions experienced following administration of Lucentis in clinical trials are 

summarised in the table below. 

 

Tabulated list of adverse reactions# 

 

The adverse reactions are listed by system organ class and frequency using the following convention: 

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), not known (cannot be estimated from the available data). Within 

each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 

 

Infections and infestations  

Very common Nasopharyngitis 

Common Urinary tract infection* 

  

Blood and lymphatic system disorders 

Common Anaemia 

  

Immune system disorders  

Common Hypersensitivity 

  

Psychiatric disorders  

Common Anxiety 

  

Nervous system disorders  

Very common Headache 

  



34 

Eye disorders  

Very common Vitritis, vitreous detachment, retinal haemorrhage, visual 

disturbance, eye pain, vitreous floaters, conjunctival 

haemorrhage, eye irritation, foreign body sensation in eyes, 

lacrimation increased, blepharitis, dry eye, ocular hyperaemia, 

eye pruritus. 

Common Retinal degeneration, retinal disorder, retinal detachment, 

retinal tear, detachment of the retinal pigment epithelium, 

retinal pigment epithelium tear, visual acuity reduced, vitreous 

haemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, 

cataract, cataract subcapsular, posterior capsule opacification, 

punctuate keratitis, corneal abrasion, anterior chamber flare, 

vision blurred, injection site haemorrhage, eye haemorrhage, 

conjunctivitis, conjunctivitis allergic, eye discharge, photopsia, 

photophobia, ocular discomfort, eyelid oedema, eyelid pain, 

conjunctival hyperaemia. 

Uncommon Blindness, endophthalmitis, hypopyon, hyphaema, 

keratopathy, iris adhesion, corneal deposits, corneal oedema, 

corneal striae, injection site pain, injection site irritation, 

abnormal sensation in eye, eyelid irritation. 

  

Respiratory, thoracic and mediastinal disorders 

Common Cough 

  

Gastrointestinal disorders  

Common Nausea 

  
Skin and subcutaneous tissue disorders 

Common Allergic reactions (rash, urticaria, pruritus, erythema) 

  
Musculoskeletal and connective tissue disorders 

Very common Arthralgia 

  

Investigations  

Very common Intraocular pressure increased 
# Adverse reactions were defined as adverse events (in at least 0.5 percentage points of patients) 

which occurred at a higher rate (at least 2 percentage points) in patients receiving treatment with 

Lucentis 0.5 mg than in those receiving control treatment (sham or verteporfin PDT). 

* observed only in DME population 

 

Product-class-related adverse reactions 

 

In the wet AMD phase III studies, the overall frequency of non-ocular haemorrhages, an adverse event 

potentially related to systemic VEGF (vascular endothelial growth factor) inhibition, was slightly 

increased in ranibizumab-treated patients. However, there was no consistent pattern among the 

different haemorrhages. There is a theoretical risk of arterial thromboembolic events, including stroke 

and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of 

arterial thromboembolic events was observed in the Lucentis clinical trials in patients with AMD, 

DME, PDR, RVO and CNV and there were no major differences between the groups treated with 

ranibizumab compared to control. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 



35 

 

4.9 Overdose 
 

Cases of accidental overdose have been reported from the clinical studies in wet AMD and post-

marketing data. Adverse reactions associated with these reported cases were intraocular pressure 

increased, transient blindness, reduced visual acuity, corneal oedema, corneal pain, and eye pain. If an 

overdose occurs, intraocular pressure should be monitored and treated, if deemed necessary by the 

attending physician. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Ophthalmologicals, antineovascularisation agents, ATC code: S01LA04 

 

Mechanism of action 

 

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human 

vascular endothelial growth factor A (VEGF-A). It binds with high affinity to the VEGF-A isoforms 

(e.g. VEGF110, VEGF121 and VEGF165), thereby preventing binding of VEGF-A to its receptors 

VEGFR-1 and VEGFR-2. Binding of VEGF-A to its receptors leads to endothelial cell proliferation 

and neovascularisation, as well as vascular leakage, all of which are thought to contribute to the 

progression of the neovascular form of age-related macular degeneration, pathologic myopia and CNV 

or to visual impairment caused by either diabetic macular oedema or macular oedema secondary to 

RVO. 

 

Clinical efficacy and safety 

 

Treatment of wet AMD 

In wet AMD, the clinical safety and efficacy of Lucentis have been assessed in three randomised, 

double-masked, sham- or active-controlled studies of 24 months duration in patients with neovascular 

AMD. A total of 1,323 patients (879 active and 444 control) were enrolled in these studies. 

 

In study FVF2598g (MARINA), 716 patients with minimally classic or occult with no classic lesions 

were randomised in a 1:1:1 ratio to receive monthly injections of Lucentis 0.3 mg, Lucentis 0.5 mg or 

sham. 

 

In study FVF2587g (ANCHOR), 423 patients with predominantly classic CNV lesions were 

randomised in a 1:1:1 ratio to receive Lucentis 0.3 mg monthly, Lucentis 0.5 mg monthly or 

verteporfin PDT (at baseline and every 3 months thereafter if fluorescein angiography showed 

persistence or recurrence of vascular leakage). 

 



36 

Key outcome measures are summarised in Table 1 and Figure 1. 

 

Table 1 Outcomes at Month 12 and Month 24 in study FVF2598g (MARINA) and FVF2587g 

(ANCHOR) 

 

  FVF2598g (MARINA) FVF2587g (ANCHOR) 

Outcome measure Month Sham 

(n=238) 

Lucentis 

0.5 mg 

(n=240) 

Verteporfin 

PDT (n=143) 

Lucentis 

0.5 mg 

(n=140) 

Loss of <15 letters in 

visual acuity (%)a 

(maintenance of 

vision, primary 

endpoint) 

Month 12 62% 95% 64% 96% 

Month 24 53% 90% 66% 90% 

Gain of ≥15 letters in 

visual acuity (%)a 

Month 12 5% 34% 6% 40% 

Month 24 4% 33% 6% 41% 

Mean change in 

visual acuity (letters) 

(SD)a 

Month 12 -10.5 (16.6) +7.2 (14.4) -9.5 (16.4) +11.3 (14.6) 

Month 24 -14.9 (18.7) +6.6 (16.5) -9.8 (17.6) +10.7 (16.5) 

a p<0.01      

 



37 

Figure 1 Mean change in visual acuity from baseline to Month 24 in study FVF2598g 

(MARINA) and study FVF2587g (ANCHOR) 
 

 
 

Results from both trials indicated that continued ranibizumab treatment may also be of benefit in 

patients who lost ≥15 letters of best-corrected visual acuity (BCVA) in the first year of treatment. 

 

Statistically significant patient-reported visual functioning benefits were observed in both MARINA 

and ANCHOR with ranibizumab treatment over the control group as measured by the NEI VFQ-25. 

 

In study FVF3192g (PIER), 184 patients with all forms of neovascular AMD were randomised in a 

1:1:1 ratio to receive Lucentis 0.3 mg, Lucentis 0.5 mg or sham injections once a month for 

3 consecutive doses, followed by a dose administered once every 3 months. From Month 14 of the 

study, sham-treated patients were allowed to receive ranibizumab and from Month 19, more frequent 

treatments were possible. Patients treated with Lucentis in PIER received a mean of 10 total 

treatments. 

 



38 

After an initial increase in visual acuity (following monthly dosing), on average, patients’ visual acuity 

declined with quarterly dosing, returning to baseline at Month 12 and this effect was maintained in 

most ranibizumab-treated patients (82%) at Month 24. Limited data from sham subjects who later 

received ranibizumab suggested that early initiation of treatment may be associated with better 

preservation of visual acuity. 

 

Data from two studies (MONT BLANC, BPD952A2308 and DENALI, BPD952A2309) conducted 

post approval confirmed the efficacy of Lucentis but did not demonstrate additional effect of the 

combined administration of verteporfin (Visudyne PDT) and Lucentis compared to Lucentis 

monotherapy. 

 

Treatment of visual impairment due to CNV secondary to PM 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to CNV in PM have 

been assessed based on the 12-month data of the double-masked, controlled pivotal study F2301 

(RADIANCE). In this study 277 patients were randomised in a 2:2:1 ratio to the following arms: 

 Group I (ranibizumab 0.5 mg, dosing regimen driven by “stability” criteria defined as no change 
in BCVA compared to two preceding monthly evaluations). 

 Group II (ranibizumab 0.5 mg, dosing regimen driven by “disease activity” criteria defined as 
vision impairment attributable to intra- or subretinal fluid or active leakage due to the CNV 

lesion as assessed by optical coherence tomography and/or fluorescence angiography). 

 Group III (vPDT - patients were allowed to receive ranibizumab treatment as of Month 3). 
In Group II, which is the recommended posology (see section 4.2), 50.9% of patients required 1 or 

2 injections, 34.5% required 3 to 5 injections and 14.7% required 6 to 12 injections over the 12-month 

study period. 62.9% of Group II patients did not require injections in the second 6 months of the study. 

 

The key outcomes from RADIANCE are summarised in Table 2 and Figure 2. 

 
Table 2 Outcomes at Month 3 and 12 (RADIANCE) 

 

 Group I 

Ranibizumab 

0.5 mg 

“vision stability” 

(n=105) 

Group II 

Ranibizumab 

0.5 mg 

“disease activity” 

(n=116) 

Group III 

vPDTb 

 

 

(n=55) 

Month 3    

Mean average BCVA change from Month 1 

to Month 3 compared to baselinea (letters) 

+10.5 +10.6 +2.2 

Proportion of patients who gained: 

≥15 letters, or reached ≥84 letters in BCVA 

 

38.1% 

 

43.1% 

 

14.5% 

Month 12    

Number of injections up to Month 12: 

Mean 

Median 

 

4.6 

4.0 

 

3.5 

2.5 

 

N/A 

N/A 

Mean average BCVA change from Month 1 

to Month 12 compared to baseline (letters) 

+12.8 +12.5 N/A 

Proportion of patients who gained: 

≥15 letters, or reached ≥84 letters in BCVA 

 

53.3% 

 

51.7% 

 

N/A 
a p<0.00001 comparison with vPDT control 
b Comparative control up to Month 3. Patients randomised to vPDT were allowed to receive 

ranibizumab treatment as of Month 3 (in Group III, 38 patients received ranibizumab as of Month 3) 

 



39 

Figure 2 Mean change from baseline BCVA over time to Month 12 (RADIANCE) 

 

The improvement of vision was accompanied by a reduction in central retinal thickness. 
 

Patient-reported benefits were observed with ranibizumab treatment arms over vPDT (p-value <0.05) 

in terms of improvement in the composite score and several subscales (general vision, near activities, 

mental health and dependency) of the NEI VFQ-25. 

 

Treatment of visual impairment due to CNV (other than secondary to PM and wet AMD) 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to CNV have been 

assessed based on the 12-month data of the double-masked, sham-controlled pivotal study G2301 

(MINERVA). In this study 178 adult patients were randomised in a 2:1 ratio to receive: 

 ranibizumab 0.5 mg at baseline, followed by an individualised dosing regimen driven by disease 
activity as assessed by visual acuity and/or anatomical parameters (e.g. VA impairment, 

intra/sub-retinal fluid, haemorrhage or leakage); 

 sham injection at baseline, followed by an individualised treatment regimen driven by disease 
activity. 

At Month 2, all patients received open-label treatment with ranibizumab as needed. 

 

Key outcome measures from MINERVA are summarised in Table 3 and Figure 3. An improvement of 

vision was observed and was accompanied by a reduction in central subfield thickness over the 

12-month period. 

 



40 

The mean number of injections given over 12 months was 5.8 in the ranibizumab arm versus 5.4 in 

those patients in the sham arm who were eligible to receive ranibizumab from Month 2 onwards. In 

the sham arm 7 out of 59 patients did not receive any treatment with ranibizumab in the study eye 

during the 12-month period. 

 

Table 3 Outcomes at Month 2 (MINERVA) 

 

 Ranibizumab 

0.5 mg (n=119) 

Sham (n=59) 

Mean BCVA change from baseline to Month 2 a  9.5 letters -0.4 letters 

Patients gaining ≥15 letters from baseline or reaching 

84 letters at Month 2 

31.4% 12.3% 

Patients not losing >15 letters from baseline at 

Month 2 

99.2% 94.7% 

Reduction in CSFTb from baseline to Month 2 a 77 µm -9.8 µm 
a One-sided p<0.001 comparison with sham control 
b CSFT - central retinal subfield thickness 

 

Figure 3 Mean change from baseline BCVA over time to Month 12 (MINERVA) 
 

 
 



41 

When comparing ranibizumab versus sham control at Month 2, a consistent treatment effect both 

overall and across baseline aetiology subgroups was observed: 

 

Table 4 Treatment effect overall and across baseline aetiology subgroups 
 

Overall and per baseline aetiology Treatment effect over 

sham [letters] 

Patient numbers [n] 

(treatment +sham) 

Overall 9.9 178 

Angioid streaks 14.6 27 

Post-inflammatory retinochoroidopathy 6.5 28 

Central serous chorioretinopathy 5.0 23 

Idiopathic chorioretinopathy 11.4 63 

Miscellaneous aetiologiesa 10.6 37 
a encompasses different aetiologies of low frequency of occurrence not included in the other subgroups 

 

In the pivotal study G2301 (MINERVA), five adolescent patients aged 12 to 17 years with visual 

impairment secondary to CNV received open-label treatment with ranibizumab 0.5 mg at baseline 

followed by an individualised treatment regimen as for the adult population. BCVA improved from 

baseline to Month 12 in all five patients, ranging from 5 to 38 letters (mean of 16.6 letters). The 

improvement of vision was accompanied by a stabilisation or reduction in central subfield thickness 

over the 12-month period. The mean number of ranibizumab injections given in the study eye over 

12 months was 3 (ranged from 2 to 5). Overall, ranibizumab treatment was well tolerated. 

 

Treatment of visual impairment due to DME 

The efficacy and safety of Lucentis have been assessed in three randomised, controlled studies of at 

least 12 months duration. A total of 868 patients (708 active and 160 control) were enrolled in these 

studies. 

 

In the phase II study D2201 (RESOLVE), 151 patients were treated with ranibizumab (6 mg/ml, n=51, 

10 mg/ml, n=51) or sham (n=49) by monthly intravitreal injections. The mean average change in 

BCVA from Month 1 to Month 12 compared to baseline was +7.8 (±7.72) letters in the pooled 

ranibizumab-treated patients (n=102), compared to -0.1 (±9.77) letters for sham-treated patients; and 

the mean change in BCVA at Month 12 from baseline was 10.3 (±9.1) letters compared to -1.4 (±14.2) 

letters, respectively (p<0.0001 for the treatment difference). 

 

In the phase III study D2301 (RESTORE), 345 patients were randomised in a 1:1:1 ratio to receive 

ranibizumab 0.5 mg monotherapy and sham laser photocoagulation, combined ranibizumab 0.5 mg 

and laser photocoagulation or sham injection and laser photocoagulation. 240 patients, who had 

previously completed the 12-month RESTORE study, were enrolled in the open-label, multicentre 

24-month extension (RESTORE Extension) study. Patients were treated with ranibizumab 0.5 mg pro 

re nata (PRN) in the same eye as the core study (D2301 RESTORE). 

 



42 

Key outcome measures are summarised in Table 5 (RESTORE and Extension) and Figure 4 

(RESTORE). 

 

Figure 4 Mean change in visual acuity from baseline over time in study D2301 (RESTORE) 

 
BL=baseline; SE=standard error of mean 

* Difference in least square means, p0.0001/0.0004 based on two-sided stratified Cochran-Mantel-

Haenszel test 

 

The effect at 12 months was consistent in most subgroups. However, subjects with a baseline BCVA 

>73 letters and macular oedema with central retinal thickness <300 µm did not appear to benefit from 

treatment with ranibizumab compared to laser photocoagulation. 

 



43 

Table 5 Outcomes at Month 12 in study D2301 (RESTORE) and at Month 36 in study 

D2301-E1 (RESTORE Extension) 

 

Outcome measures at Month 12 compared 

to baseline in study D2301 (RESTORE) 

Ranibizumab 

0.5 mg 

n=115 

Ranibizumab 

0.5 mg + Laser 

n=118 

Laser 

 

n=110 

Mean average change in BCVA from 

Month 1 to Month 12a (SD) 

6.1 (6.4)a 5.9 (7.9)a 0.8 (8.6) 

Mean change in BCVA at Month 12 

(SD) 

6.8 (8.3)a 6.4 (11.8)a 0.9 (11.4) 

Gain of ≥15 letters or BCVA ≥84 letters at 

Month 12 (%) 

22.6 22.9 8.2 

Mean number of injections (Months 0-11) 7.0  6.8 7.3 (sham) 

 

Outcome measure at Month 36 compared 

to D2301 (RESTORE) baseline in study 

D2301-E1 (RESTORE Extension) 

Prior ranibizumab 

0.5 mg 

n=83 

Prior ranibizumab 

0.5 mg + laser 

n=83 

Prior laser 

 

n=74 

Mean change in BCVA at Month 24 (SD) 7.9 (9.0) 6.7 (7.9) 5.4 (9.0) 

Mean change in BCVA at Month 36 (SD) 8.0 (10.1) 6.7 (9.6) 6.0 (9.4) 

Gain of ≥15 letters or BCVA ≥84 letters at 

Month 36 (%) 
27.7 30.1 21.6 

Mean number of injections 

(Months 12-35)* 
6.8 6.0 6.5 

ap<0.0001 for comparisons of ranibizumab arms vs. laser arm. 

n in D2301-E1 (RESTORE Extension) is the number of patients with a value at both D2301 

(RESTORE) baseline (Month 0) and at the Month 36 visit. 

* The proportion of patients who did not require any ranibizumab treatment during the extension 

phase was 19%, 25% and 20% in the prior ranibizumab, prior ranibizumab + laser and prior laser 

groups, respectively. 

 

Statistically significant patient-reported benefits for most vision-related functions were observed with 

ranibizumab (with or without laser) treatment over the control group as measured by the NEI VFQ-25. 

For other subscales of this questionnaire no treatment differences could be established. 

 

The long-term safety profile of ranibizumab observed in the 24-month extension study is consistent 

with the known Lucentis safety profile. 

 

In the phase IIIb study D2304 (RETAIN), 372 patients were randomised in 1:1:1 ratio to receive: 

 ranibizumab 0.5 mg with concomitant laser photocoagulation on a treat-and-extend (TE) 
regimen, 

 ranibizumab 0.5 mg monotherapy on a TE regimen, 

 ranibizumab 0.5 mg monotherapy on a PRN regimen. 
 

In all groups, ranibizumab was administered monthly until BCVA was stable for at least three 

consecutive monthly assessments. On TE, ranibizumab was administered at treatment intervals of 

2-3 months. In all groups, monthly treatment was re-initiated upon a decrease in BCVA due to DME 

progression and continued until stable BCVA was reached again. 

 

The number of scheduled treatment visits after the initial 3 injections, was 13 and 20 for the TE and 

PRN regimens, respectively. With both TE regimens, more than 70% of patients maintained their 

BCVA with an average visit frequency of ≥2 months. 

 



44 

The key outcome measures are summarised in Table 6. 

 

Table 6 Outcomes in study D2304 (RETAIN) 

 

Outcome measure 

compared to baseline 

TE ranibizumab 

0.5 mg + laser 

n=117 

TE ranibizumab 

0.5 mg alone 

n=125 

PRN ranibizumab 

0.5 mg 

n=117 

Mean average change 

in BCVA from 

Month 1 to Month 12 

(SD) 

5.9 (5.5) a 6.1 (5.7) a 6.2 (6.0) 

Mean average change 

in BCVA from 

Month 1 to Month 24 

(SD) 

6.8 (6.0) 6.6 (7.1) 7.0 (6.4) 

Mean change in BCVA 

at Month 24 (SD) 
8.3 (8.1) 6.5 (10.9) 8.1 (8.5) 

Gain of ≥15 letters or 

BCVA ≥84 letters at 

Month 24(%) 

25.6 28.0 30.8 

Mean number of 

injections 

(months 0-23) 

12.4 12.8 10.7 

ap<0.0001 for assessment of non-inferiority to PRN 

 

In DME studies, the improvement in BCVA was accompanied by a reduction over time in mean CSFT 

in all the treatment groups. 

 

Treatment of PDR 

The clinical safety and efficacy of Lucentis in patients with PDR have been assessed in Protocol S 

which evaluated the treatment with ranibizumab 0.5 mg intravitreal injections compared with 

panretinal photocoagulation (PRP). The primary endpoint was the mean visual acuity change at year 2. 

Additionally, change in diabetic retinopathy (DR) severity was assessed based on fundus photographs 

using the DR severity score (DRSS). 

 

Protocol S was a multicentre, randomised, active-controlled, parallel-assignment, non-inferiority 

phase III study in which 305 patients (394 study eyes) with PDR with or without DME at baseline 

were enrolled. The study compared ranibizumab 0.5 mg intravitreal injections to standard treatment 

with PRP. A total of 191 eyes (48.5%) were randomised to ranibizumab 0.5 mg and 203 eyes (51.5%) 

eyes were randomised to PRP. A total of 88 eyes (22.3%) had baseline DME: 42 (22.0%) and 

46 (22.7%) eyes in the ranibizumab and PRP groups, respectively. 

 

In this study, the mean visual acuity change at year 2 was +2.7 letters in the ranibizumab group 

compared to -0.7 letters in the PRP group. The difference in least square means was 3.5 letters (95% 

CI: [0.2 to 6.7]). 

 

At year 1, 41.8% of eyes experienced a ≥2-step improvement in the DRSS when treated with 

ranibizumab (n=189) compared to 14.6% of eyes treated with PRP (n=199). The estimated difference 

between ranibizumab and laser was 27.4% (95% CI: [18.9, 35.9]). 

 



45 

Table 7 DRSS improvement or worsening of ≥2 or ≥3 steps at year 1 in Protocol S (LOCF 

Method) 

 

Categorised change 

from baseline 

Protocol S 

Ranibizumab 

0.5 mg 

(N=189) 

PRP 

(N=199) 

Difference in 

proportion (%), CI 

≥2-step improvement 

n (%) 79 

(41.8%) 

29 

(14.6%) 

27.4 

(18.9, 35.9) 

≥3-step improvement 

n (%) 54 

(28.6%) 

6 

(3.0%) 

25.7 

(18.9, 32.6) 

≥2-step worsening 

n (%) 3 

(1.6%) 

23 

(11.6%) 

-9.9 

(-14.7, -5.2) 

≥3-step worsening 

n (%) 1 

(0.5%) 

8 

(4.0%) 

-3.4 

(-6.3, -0.5) 

DRSS = diabetic retinopathy severity score, n = number of patients who satisfied the condition at 

the visit, N = total number of study eyes. 

 

At year 1 in the ranibizumab-treated group in Protocol S, ≥2-step improvement in DRSS was 

consistent in eyes without DME (39.9%) and with baseline DME (48.8%). 

 

An analysis of year 2 data from Protocol S demonstrated that 42.3% (n=80) of eyes in the 

ranibizumab-treated group had ≥2-step improvement in DRSS from baseline compared with 23.1% 

(n=46) of eyes in the PRP group. In the ranibizumab-treated group, ≥2-step improvement in DRSS 

from baseline was observed in 58.5% (n=24) of eyes with baseline DME and 37.8% (n=56) of eyes 

without DME. 

 

DRSS was also assessed in three separate active-controlled phase III DME studies (ranibizumab 

0.5 mg PRN vs laser) that included a total of 875 patients, of whom approximately 75% were of Asian 

origin. In a meta-analysis of these studies, 48.4% of the 315 patients with gradable DRSS scores in the 

subgroup of patients with moderately severe non-proliferative DR (NPDR) or worse at baseline 

experienced a ≥2-step improvement in the DRSS at Month 12 when treated with ranibizumab (n=192) 

vs 14.6% of patients treated with laser (n=123). The estimated difference between ranibizumab and 

laser was 29.9% (95% CI: [20.0, 39.7]). In the 405 DRSS gradable patients with moderate NPDR or 

better, a ≥2-step DRSS improvement was observed in 1.4% and 0.9% of the ranibizumab and laser 

groups, respectively. 

 

Treatment of visual impairment due to macular oedema secondary to RVO 

The clinical safety and efficacy of Lucentis in patients with visual impairment due to macular oedema 

secondary to RVO have been assessed in the randomised, double-masked, controlled studies BRAVO 

and CRUISE that recruited subjects with BRVO (n=397) and CRVO (n=392), respectively. In both 

studies, subjects received either 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, 

patients in the sham-control arms switched to 0.5 mg ranibizumab. 

 



46 

Key outcome measures from BRAVO and CRUISE are summarised in Table 8 and Figures 5 and 6. 

 

Table 8 Outcomes at Month 6 and 12 (BRAVO and CRUISE) 

 

 BRAVO CRUISE 

 Sham/Lucentis 

0.5 mg 

(n=132) 

Lucentis 

0.5 mg 

(n=131) 

Sham/Lucentis 

0.5 mg 

(n=130) 

Lucentis 

0.5 mg 

(n=130) 

Mean change in visual acuity 

at Month 6a (letters) (SD) 

(primary endpoint) 

7.3 (13.0) 18.3 (13.2) 0.8 (16.2) 14.9 (13.2) 

Mean change in BCVA at 

Month 12 (letters) (SD) 

12.1 (14.4) 18.3 (14.6) 7.3 (15.9) 13.9 (14.2) 

Gain of ≥15 letters in visual 

acuity at Month 6a (%) 

28.8 61.1 16.9 47.7 

Gain of ≥15 letters in visual 

acuity at Month 12 (%) 

43.9 60.3 33.1 50.8 

Proportion (%) receiving 

laser rescue over 12 months 

61.4 34.4 NA NA 

ap<0.0001for both studies 

 

Figure 5 Mean change from baseline BCVA over time to Month 6 and Month 12 (BRAVO) 

 

 
 



47 

Figure 6 Mean change from baseline BCVA over time to Month 6 and Month 12 (CRUISE) 

 

 
In both studies, the improvement of vision was accompanied by a continuous and significant reduction 

in the macular oedema as measured by central retinal thickness. 

 

In patients with CRVO (CRUISE and extension study HORIZON): Subjects treated with sham in the 

first 6 months who subsequently received ranibizumab did not achieve comparable gains in VA by 

Month 24 (~6 letters) compared to subjects treated with ranibizumab from study start (~12 letters). 

 

Statistically significant patient-reported benefits in subscales related to near and distance activity were 

observed with ranibizumab treatment over the control group as measured by the NEI VFQ-25. 

 

The long-term (24 months) clinical safety and efficacy of Lucentis in patients with visual impairment 

due to macular oedema secondary to RVO were assessed in the BRIGHTER (BRVO) and CRYSTAL 

(CRVO) studies. In both studies, subjects received a 0.5 mg ranibizumab PRN dosing regimen driven 

by individualised stabilisation criteria. BRIGHTER was a 3-arm randomised active-controlled study 

that compared 0.5 mg ranibizumab given as monotherapy or in combination with adjunctive laser 

photocoagulation to laser photocoagulation alone. After 6 months, subjects in the laser arm could 

receive 0.5 mg ranibizumab. CRYSTAL was a single-arm study with 0.5 mg ranibizumab 

monotherapy. 

 



48 

Key outcome measures from BRIGHTER and CRYSTAL are shown in Table 9. 

 

Table 9 Outcomes at Months 6 and 24 (BRIGHTER and CRYSTAL) 

 

 BRIGHTER CRYSTAL 
 Lucentis 0.5 mg 

N=180 
Lucentis 0.5 mg 

+ Laser 

N=178 

Laser* 

N=90 
Lucentis 0.5 mg 

N=356 

Mean change in 

BCVA at 

Month 6a (letters) 

(SD) 

+14.8 

(10.7) 
+14.8 

(11.13) 
+6.0 

(14.27) 
+12.0 

(13.95) 

Mean change in 

BCVA at 

Month 24b 

(letters) (SD) 

+15.5 

(13.91) 
+17.3 

(12.61) 
+11.6 

(16.09) 
+12.1 

(18.60) 

Gain of 

≥15 letters in 

BCVA at 

Month 24 (%) 

52.8 59.6 43.3 49.2 

Mean number of 

injections (SD) 

(months 0-23) 

11.4 

(5.81) 
11.3 (6.02) NA 13.1 (6.39) 

a p<0.0001for both comparisons in BRIGHTER at Month 6: Lucentis 0.5 mg vs Laser and 

Lucentis 0.5 mg + Laser vs Laser. 
b p<0.0001for null hypothesis in CRYSTAL that the mean change at Month 24 from baseline 

is zero. 

* Starting at Month 6 ranibizumab 0.5 mg treatment was allowed (24 patients were treated with 

laser only). 

 

In BRIGHTER, ranibizumab 0.5 mg with adjunctive laser therapy demonstrated non-inferiority versus 

ranibizumab monotherapy from baseline to Month 24 (95% CI -2.8, 1.4). 

 

In both studies, a rapid and statistically significant decrease from baseline in central retinal subfield 

thickness was observed at Month 1. This effect was maintained up to Month 24. 

 

The effect of ranibizumab treatment was similar irrespective of the presence of retinal ischaemia. In 

BRIGHTER, patients with ischaemia present (N=46) or absent (N=133) and treated with ranibizumab 

monotherapy had a mean change from baseline of +15.3 and +15.6 letters, respectively, at Month 24. 

In CRYSTAL, patients with ischaemia present (N=53) or absent (N=300) and treated with 

ranibizumab monotherapy had a mean change from baseline of +15.0 and +11.5 letters, respectively. 

 

The effect in terms of visual improvement was observed in all patients treated with 0.5 mg 

ranibizumab monotherapy regardless of their disease duration in both BRIGHTER and CRYSTAL. In 

patients with <3 months disease duration an increase in visual acuity of 13.3 and 10.0 letters was seen 

at Month 1; and 17.7 and 13.2 letters at Month 24 in BRIGHTER and CRYSTAL, respectively. The 

corresponding visual acuity gain in patients with ≥12 months disease duration was 8.6 and 8.4 letters 

in the respective studies. Treatment initiation at the time of diagnosis should be considered. 

 

The long-term safety profile of ranibizumab observed in the 24-month studies is consistent with the 

known Lucentis safety profile. 

 

  



49 

Paediatric population 

 

The safety and efficacy of ranibizumab have not yet been established in paediatric patients. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Lucentis in all subsets of the paediatric population in neovascular AMD, visual impairment due to 

DME, visual impairment due to macular oedema secondary to RVO and visual impairment due to 

CNV and diabetic retinopathy (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 
 

Following monthly intravitreal administration of Lucentis to patients with neovascular AMD, serum 

concentrations of ranibizumab were generally low, with maximum levels (Cmax) generally below the 

ranibizumab concentration necessary to inhibit the biological activity of VEGF by 50% (11-27 ng/ml, 

as assessed in an in vitro cellular proliferation assay). Cmax was dose proportional over the dose range 

of 0.05 to 1.0 mg/eye. Serum concentrations in a limited number of DME patients indicate that a 

slightly higher systemic exposure cannot be excluded compared to those observed in neovascular 

AMD patients. Serum ranibizumab concentrations in RVO patients were similar or slightly higher 

compared to those observed in neovascular AMD patients. 

 

Based on analysis of population pharmacokinetics and disappearance of ranibizumab from serum for 

patients with neovascular AMD treated with the 0.5 mg dose, the average vitreous elimination half-life 

of ranibizumab is approximately 9 days. Upon monthly intravitreal administration of Lucentis 

0.5 mg/eye, serum ranibizumab Cmax, attained approximately 1 day after dosing, is predicted to 

generally range between 0.79 and 2.90 ng/ml, and Cmin is predicted to generally range between 0.07 

and 0.49 ng/ml. Serum ranibizumab concentrations are predicted to be approximately 90,000-fold 

lower than vitreal ranibizumab concentrations. 

 

Patients with renal impairment: No formal studies have been conducted to examine the 

pharmacokinetics of Lucentis in patients with renal impairment. In a population pharmacokinetic 

analysis of neovascular AMD patients, 68% (136 of 200) of patients had renal impairment (46.5% 

mild [50-80 ml/min], 20% moderate [30-50 ml/min], and 1.5% severe [<30 ml/min]). In RVO 

patients, 48.2% (253 of 525) had renal impairment (36.4% mild, 9.5% moderate and 2.3% severe). 

Systemic clearance was slightly lower, but this was not clinically significant. 

 

Hepatic impairment: No formal studies have been conducted to examine the pharmacokinetics of 

Lucentis in patients with hepatic impairment. 

 

5.3 Preclinical safety data 
 

Bilateral intravitreal administration of ranibizumab to cynomolgus monkeys at doses between 

0.25 mg/eye and 2.0 mg/eye once every 2 weeks for up to 26 weeks resulted in dose-dependent ocular 

effects. 

 

Intraocularly, there were dose-dependent increases in anterior chamber flare and cells with a peak 

2 days after injection. The severity of the inflammatory response generally diminished with 

subsequent injections or during recovery. In the posterior segment, there were vitreal cell infiltration 

and floaters, which also tended to be dose-dependent and generally persisted to the end of the 

treatment period. In the 26-week study, the severity of the vitreous inflammation increased with the 

number of injections. However, evidence of reversibility was observed after recovery. The nature and 

timing of the posterior segment inflammation is suggestive of an immune-mediated antibody response, 

which may be clinically irrelevant. Cataract formation was observed in some animals after a relatively 

long period of intense inflammation, suggesting that the lens changes were secondary to severe 

inflammation. A transient increase in post-dose intraocular pressure was observed following 

intravitreal injections, irrespective of dose. 

 



50 

Microscopic ocular changes were related to inflammation and did not indicate degenerative processes. 

Granulomatous inflammatory changes were noted in the optic disc of some eyes. These posterior 

segment changes diminished, and in some instances resolved, during the recovery period. 

 

Following intravitreal administration, no signs of systemic toxicity were detected. Serum and vitreous 

antibodies to ranibizumab were found in a subset of treated animals. 

 

No carcinogenicity or mutagenicity data are available. 

 

In pregnant monkeys, intravitreal ranibizumab treatment resulting in maximal systemic exposures 

0.9-7-fold a worst case clinical exposure did not elicit developmental toxicity or teratogenicity, and 

had no effect on weight or structure of the placenta, although, based on its pharmacological effect 

ranibizumab should be regarded as potentially teratogenic and embryo-/foetotoxic. 

 

The absence of ranibizumab-mediated effects on embryo-foetal development is plausibly related 

mainly to the inability of the Fab fragment to cross the placenta. Nevertheless, a case was described 

with high maternal ranibizumab serum levels and presence of ranibizumab in foetal serum, suggesting 

that the anti-ranibizumab antibody acted as (Fc region containing) carrier protein for ranibizumab, 

thereby decreasing its maternal serum clearance and enabling its placental transfer. As the embryo-

foetal development investigations were performed in healthy pregnant animals and disease (such as 

diabetes) may modify the permeability of the placenta towards a Fab fragment, the study should be 

interpreted with caution. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

α,α-trehalose dihydrate 

Histidine hydrochloride, monohydrate 

Histidine 

Polysorbate 20 

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 
 

3 years 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Keep the pre-filled syringe in its sealed tray in the carton in order to protect from light. 

Prior to use, the unopened tray may be kept at room temperature (25°C) for up to 24 hours. 

 

  



51 

6.5 Nature and contents of container 

 

0.165 ml sterile solution in a pre-filled syringe (type I glass) with a bromobutyl rubber plunger stopper 

and a syringe cap consisting of a white, tamper-evident rigid seal with a grey bromobutyl rubber tip 

cap including a Luer lock adapter. The pre-filled syringe has a plunger rod and a finger grip, and is 

packed in a sealed tray. 

 

Pack size of one pre-filled syringe. 

 

6.6 Special precautions for disposal and other handling 
 

The pre-filled syringe is for single use only. The pre-filled syringe is sterile. Do not use the product if 

the packaging is damaged. The sterility of the pre-filled syringe cannot be guaranteed unless the tray 

remains sealed. Do not use the pre-filled syringe if the solution is discoloured, cloudy or contains 

particles. 

 

The pre-filled syringe contains more than the recommended dose of 0.5 mg. The extractable volume of 

the pre-filled syringe (0.1 ml) is not to be used in total. The excess volume should be expelled prior to 

injection. Injecting the entire volume of the pre-filled syringe could result in overdose. To expel the air 

bubble along with the excess medicinal product, slowly push the plunger until the edge below the 

dome of the rubber stopper is aligned with the black dosing line on the syringe (equivalent to 0.05 ml, 

i.e., 0.5 mg ranibizumab). 

 

For the intravitreal injection, a 30G x ½″ sterile injection needle should be used. 

 

To prepare Lucentis for intravitreal administration, please adhere to the instructions for use: 

 

Introduction Read all the instructions carefully before using the pre-filled syringe. 

The pre-filled syringe is for single use only. The pre-filled syringe is sterile. Do 

not use the product if the packaging is damaged. The opening of the sealed tray 

and all subsequent steps should be done under aseptic conditions. 

Note: The dose must be set to 0.05 ml. 

Pre-filled 

syringe 

description 

 

 

 

 

 

Prepare 1. Make sure that the pack contains: 

 a sterile pre-filled syringe in a sealed tray. 
2. Peel the lid off the syringe tray and, using aseptic technique, carefully 

remove the syringe. 

Syringe cap 0.05 ml dose mark Finger grip 

Plunger rod Rubber stopper Luer lock 

Figure 1 



52 

Check syringe 3. Check that: 

 the syringe cap is not detached from the 
Luer lock. 

 the syringe is not damaged. 

 the solution looks clear, colourless to pale 
yellow and does not contain any particles. 

4. If any of the above is not true, discard the 

pre-filled syringe and use a new one. 

 

Remove 

syringe cap 

5. Snap off (do not turn or twist) the syringe 

cap (see Figure 2). 

6. Dispose of the syringe cap (see Figure 3). 

 
Figure 2 

 

 
Figure 3 

Attach needle 7. Attach a 30G x ½″ sterile injection needle 

firmly onto the syringe by screwing it 

tightly onto the Luer lock (see Figure 4). 

8. Carefully remove the needle cap by 

pulling it straight off (see Figure 5). 

Note: Do not wipe the needle at any time. 

 

 
Figure 4 Figure 5 



53 

Dislodge air 

bubbles 

9. Hold the syringe upright. 

10. If there are any air bubbles, gently tap the 

syringe with your finger until the bubbles 

rise to the top (see Figure 6). 

 

 
Figure 6 

 

Set dose 11. Hold the syringe at eye level and 

carefully push the plunger until the edge 

below the dome of the rubber stopper 
is aligned with the dose mark (see 

Figure 7). This will expel the air and the 

excess solution and set the dose to 

0.05 ml. 

Note: The plunger rod is not attached to the 

rubber stopper – this is to prevent air being 

drawn into the syringe. 

 

 
Figure 7 

Inject The injection procedure should be carried out under aseptic conditions. 

12. The injection needle should be inserted 3.5-4.0 mm posterior to the limbus 

into the vitreous cavity, avoiding the horizontal meridian and aiming towards 

the centre of the globe. 

13. Inject slowly until the rubber stopper reaches the bottom of the syringe to 

deliver the volume of 0.05 ml. 

14. A different scleral site should be used for subsequent injections. 

15. After injection, do not recap the needle or detach it from the syringe. Dispose 

of the used syringe together with the needle in a sharps disposal container or 

in accordance with local requirements. 

 

 



54 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/374/003 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22 January 2007 

Date of latest renewal: 11 November 2016 

 

 

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 

  



55 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURERS RESPONSIBLE 

FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 



56 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer of the biological active substance 

 

Roche Singapore Technical Operations Pte. Ltd. 

10 Tuas Bay Link 

Singapore 637394 
Singapore 

 

Name and address of the manufacturers responsible for batch release 

 

Solution for injection 

Novartis Pharma GmbH 
Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Solution for injection in pre-filled syringe 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Alcon-Couvreur NV 

Rijksweg 14 

2870 Puurs 

Belgium 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2) 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

  



57 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 

AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

 At request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 Additional risk minimisation measures 
 

Prior to launch in each Member State the MAH shall agree the final educational material with the 

National Competent Authority. 

 

The MAH shall ensure that, following discussions and agreements with the National Competent 

Authorities in each Member State where Lucentis is marketed, at launch and after launch all 

ophthalmological clinics where Lucentis is expected to be used are provided with an up-to-date patient 

information pack. 

 

The patient information pack should be provided in both the form of patient information booklets and 

an audio-CD that contain following key elements: 

 Patient information leaflet 

 How to prepare for Lucentis treatment 

 What are the steps following treatment with Lucentis 

 Key signs and symptoms of serious adverse events including increased intraocular pressure, 
intraocular inflammation, retinal detachment & retinal tear and infectious endophthalmitis 

 When to seek urgent attention from the health care provider 
 

 

 Obligation to conduct post-authorisation measures 
 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Description Due date 

Post-authorisation efficacy study (PAES): CRFB002H2301E1 

 

In order to verify the impact of the intervention on clinical outcome or 

disease progression and to confirm previous efficacy assumptions, the 

MAH should conduct and submit the results of the ongoing 

prospective, open-label, multicentre study. 

Interim reports: 

 

IA2 

 

30-Jun-2020 

 

Final study report: 

 

30-Jun-2023 

 

  



58 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



59 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



60 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One ml contains 10 mg of ranibizumab. Vial containing 2.3 mg of ranibizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; histidine; 

polysorbate 20; water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection 

 

1x 0.23 ml vial 

Single dose for adults: 0.5 mg/0.05 ml. Excess volume to be expelled. 

Single dose for babies born prematurely: 0.2 mg/0.02 ml. Excess volume to be expelled. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravitreal use. 

Vial for single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



61 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Keep the vial in the outer carton 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 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/374/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



62 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

LABEL 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

Intravitreal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2.3 mg/0.23 ml 

 

 

6. OTHER 

 

  



63 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Lucentis 10 mg/ml solution for injection in pre-filled syringe 

ranibizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each pre-filled syringe of 0.165 ml solution contains 1.65 mg of ranibizumab (10 mg/ml). 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; histidine; 

polysorbate 20; water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection 

 

1 pre-filled syringe of 0.165 ml. 

Single dose of 0.5 mg/0.05 ml. 

Excess volume should be expelled prior to injection. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single use only. Upon opening of the sealed tray, proceed under aseptic conditions. 

Set dose to 0.05 ml dose mark. 

Read the package leaflet before use. 

Intravitreal use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 



64 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Keep the pre-filled syringe in its sealed tray in the carton to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/374/003 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



65 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

BLISTER FOIL 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Lucentis 10 mg/ml solution for injection in pre-filled syringe 

ranibizumab 

Intravitreal use 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

0.165 ml 

 

  



66 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

LABEL 

 

PRE-FILLED SYRINGE 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

Intravitreal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

0.165 ml 

 

 

6. OTHER 

 

  



67 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

VIAL + FILTER NEEDLE 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One ml contains 10 mg of ranibizumab. Vial containing 2.3 mg of ranibizumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; histidine; 

polysorbate 20; water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection 

 

1x 0.23 ml vial, 1 filter needle. 

Single dose for adults: 0.5 mg/0.05 ml. Excess volume to be expelled. 

Single dose for babies born prematurely: 0.2 mg/0.02 ml. Excess volume to be expelled. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravitreal use. 

Vial and filter needle for single use only. 

Read the package leaflet before use. 

The filter needle is not for injection. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 



68 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator (2C - 8C). 

Do not freeze. 

Keep the vial in the outer carton 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 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/06/374/004 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



69 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

LABEL 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

Intravitreal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2.3 mg/0.23 ml 

 

 

6. OTHER 

 

  



70 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



71 

Package leaflet: Information for the adult patient 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

 

ADULTS 

 

Please find information for babies born prematurely on the other side of this leaflet. 

 

Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor. 

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 

 

What is in this leaflet 
1. What Lucentis is and what it is used for 

2. What you need to know before you are given Lucentis 

3. How Lucentis is given 

4. Possible side effects 

5. How to store Lucentis 

6. Contents of the pack and other information 

 

 

1. What Lucentis is and what it is used for 

 

What Lucentis is 

Lucentis is a solution which is injected into the eye. Lucentis belongs to a group of medicines called 

antineovascularisation agents. It contains the active substance called ranibizumab. 

 

What Lucentis is used for 

Lucentis is used in adults to treat several eye diseases causing vision impairment. 

 

These diseases result from damage to the retina (light-sensitive layer at the back of the eye) caused by: 

- Growth of leaky, abnormal blood vessels. This is observed in diseases such as age-related 

macular degeneration (AMD) and proliferative diabetic retinopathy (PDR, a disease caused by 

diabetes). It may also be associated with choroidal neovascularisation (CNV) due to pathologic 

myopia (PM), angioid streaks, central serous chorioretinopathy or inflammatory CNV. 

- Macular oedema (swelling of the centre of the retina). This swelling can be caused by diabetes 

(a disease called diabetic macular oedema (DME)) or by the blockage of retinal veins of the 

retina (a disease called retinal vein occlusion (RVO)). 

 

How Lucentis works 

Lucentis specifically recognises and binds to a protein called human vascular endothelial growth 

factor A (VEGF-A) present in the eye. In excess, VEGF-A causes abnormal blood vessel growth and 

swelling in the eye which can lead to impairment of vision in diseases like AMD, DME, PDR, RVO, 

PM and CNV. By binding to VEGF-A, Lucentis can block its actions and prevent this abnormal 

growth and swelling. 

 

In these diseases, Lucentis can help to stabilise and in many cases improve your vision. 

 

 

  



72 

2. What you need to know before you are given Lucentis 

 

You must not receive Lucentis 

- If you are allergic to ranibizumab or any of the other ingredients of this medicine (listed in 

section 6). 

- If you have an infection in or around your eye. 

- If you have pain or redness (severe intraocular inflammation) in your eye. 

 

Warnings and precautions 

Talk to your doctor before you are given Lucentis. 

- Lucentis is given as an injection into the eye. Occasionally, an infection in the internal portion 

of the eye, pain or redness (inflammation), detachment or tear of one of the layers in the back of 

the eye (retinal detachment or tear and retinal pigment epithelial detachment or tear), or 

clouding of the lens (cataract) may occur after Lucentis treatment. It is important to identify and 

treat such an infection or retinal detachment as soon as possible. Please tell your doctor 

immediately if you develop signs such as eye pain or increased discomfort, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in your vision or 

increased sensitivity to light. 

- In some patients the eye pressure may increase for a short period directly after the injection. 

This is something you may not notice, therefore your doctor may monitor this after each 

injection. 

- Inform your doctor if you have a prior history of eye conditions or eye treatments, or if you 

have had a stroke or experienced transient signs of stroke (weakness or paralysis of limbs or 

face, difficulty speaking or understanding). This information will be taken into account to 

evaluate if Lucentis is the appropriate treatment for you. 

 

Please see section 4 (“Possible side effects”) for more detailed information on side effects that could 

occur during Lucentis therapy. 

 

Children and adolescents (below 18 years of age) 

Except for retinopathy of prematurity, the use of Lucentis in children and adolescents has not been 

established and is therefore not recommended. For the treatment of babies born prematurely with 

retinopathy of prematurity (ROP) please see the other side of this leaflet. 

 

Other medicines and Lucentis 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding 
- Women who could become pregnant must use effective contraception during treatment and for 

at least three further months after the last injection of Lucentis. 

- There is no experience of using Lucentis in pregnant women. Lucentis should not be used 
during pregnancy unless the potential benefit outweighs the potential risk to the unborn child. If 

you are pregnant, think you may be pregnant or planning to become pregnant, discuss this with 

your doctor before treatment with Lucentis. 

- Lucentis is not recommended during breast-feeding because it is not known whether Lucentis 
passes into human milk. Ask your doctor or pharmacist for advice before Lucentis treatment. 

 

Driving and using machines 

After Lucentis treatment you may experience some temporary vision blurring. If this happens, do not 

drive or use machines until this resolves. 

 

 



73 

3. How Lucentis is given 

 

Lucentis is administered as a single injection into your eye by your eye doctor under a local 

anaesthetic. The usual dose of an injection is 0.05 ml (which contains 0.5 mg of active substance). The 

interval between two doses injected into the same eye should be at least four weeks. All injections will 

be administered by your eye doctor. 

 

Before the injection, your doctor will wash your eye carefully to prevent infection. Your doctor will 

also give you a local anaesthetic to reduce or prevent any pain you might have with the injection. 

 

The treatment is started with one injection of Lucentis per month. Your doctor will monitor the 

condition of your eye and, depending on how you respond to the treatment, will decide if and when 

you need to receive further treatment. 

 

Detailed instructions for use are given at the end of the leaflet under “How to prepare and administer 

Lucentis”. 

 

Elderly (age 65 years and over) 

Lucentis can be used for people of 65 years of age and over without dose adjustment. 

 

Before stopping Lucentis treatment 

If you are considering stopping Lucentis treatment, please go to your next appointment and discuss 

this with your doctor. Your doctor will advise you and decide how long you should be treated with 

Lucentis. 

 

If you have any further questions on the use of this medicine, ask your doctor. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The side effects associated with the administration of Lucentis are either due to the medicine itself or 

the injection procedure and mostly affect the eye. 

 

The most serious side effects are described below: 

Common serious side effects (may affect up to 1 in 10 people): Detachment or tear of the layer in the 

back of the eye (retinal detachment or tear), resulting in flashes of light with floaters progressing to a 

temporary loss of sight, or a clouding of the lens (cataract). 

Uncommon serious side effects (may affect up to 1 in 100 people): Blindness, infection of the eyeball 

(endophthalmitis) with inflammation of the inside of the eye. 

 

The symptoms you might experience are pain or increased discomfort in your eye, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in your vision or increased 

sensitivity to light. Please tell your doctor immediately if you develop any of these side effects. 

 

The most frequently reported side effects are described below: 

Very common side effects (may affect more than 1 in 10 people) 

Visual side effects include: Inflammation of the eye, bleeding in the back of the eye (retinal bleeding), 

visual disturbances, eye pain, small particles or spots in your vision (floaters), bloodshot eye, eye 

irritation, a feeling of having something in the eye, increased tear production, inflammation or 

infection of the eyelid margins, dry eye, redness or itching of the eye and increased eye pressure. 

Non-visual side effects include: Sore throat, nasal congestion, runny nose, headache and joint pain. 

 



74 

Other side effects which may occur following Lucentis treatment are described below: 

Common side effects 
Visual side effects include: Decreased sharpness of vision, swelling of a section of the eye (uvea, 

cornea), inflammation of the cornea (front part of eye), small marks on the surface of the eye, blurred 

vision, bleeding at the site of injection, bleeding in the eye, discharge from the eye with itching, 

redness and swelling (conjunctivitis), light sensitivity, eye discomfort, swelling of the eyelid, eyelid 

pain. 

Non-visual side effects include: Urinary tract infection, low red blood cells count (with symptoms 

such as tiredness, breathlessness, dizziness, pale skin), anxiety, cough, nausea, allergic reactions like 

rash, hives, itching and skin reddening. 

 

Uncommon side effects 
Visual side effects include: Inflammation and bleeding in the front part of the eye, sac of pus on the 

eye, changes of the central part of the eye surface, pain or irritation at the site of injection, abnormal 

sensation in the eye, irritation of the eyelid. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 

By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Lucentis 
 

- Keep this medicine out of the sight and reach of children. 

- Do not use this medicine after the expiry date which is stated on the carton and vial label after 
EXP. The expiry date refers to the last day of that month. 

- Store in a refrigerator (2°C – 8°C). Do not freeze. 

- Prior to use, the unopened vial may be kept at room temperature (25°C) for up to 24 hours. 

- Keep the vial in the outer carton in order to protect from light. 

- Do not use any pack that is damaged. 

 

 

6. Contents of the pack and other information 

 

What Lucentis contains 

- The active substance is ranibizumab. Each ml contains 10 mg ranibizumab. Each vial contains 

2.3 mg ranibizumab in 0.23 ml solution. This provides a suitable amount to deliver a single dose 

of 0.05 ml containing 0.5 mg ranibizumab. 

- The other ingredients are α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; 

histidine; polysorbate 20; water for injections. 

 

What Lucentis looks like and contents of the pack 

Lucentis is a solution for injection in a vial (0.23 ml). The solution is clear, colourless to pale yellow 

and aqueous. 

 

Two different pack types are available: 

 

Vial-only pack 

Pack containing one glass vial of ranibizumab with chlorobutyl rubber stopper. The vial is for single 

use only. 

 

Vial + filter needle pack 

Pack containing one glass vial of ranibizumab with chlorobutyl rubber stopper and one blunt filter 

needle (18G x 1½″, 1.2 mm x 40 mm, 5 micrometres) for withdrawal of the vial contents. All 

components are for single use only. 

 



75 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 



76 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 



77 

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE 

PROFESSIONALS ONLY: 
 

Please also refer to section 3 “How Lucentis is given”. 

 

How to prepare and administer Lucentis to adults 

 

Single-use vial for intravitreal use only 

 

Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections. 

 

In wet AMD, in CNV, in PDR and in visual impairment due to DME or to macular oedema secondary 

to RVO the recommended dose for Lucentis is 0.5 mg given as a single intravitreal injection. This 

corresponds to an injection volume of 0.05 ml. The interval between two doses injected into the same 

eye should be at least four weeks. 

 

Treatment is initiated with one injection per month until maximum visual acuity is achieved and/or 

there are no signs of disease activity i.e. no change in visual acuity and in other signs and symptoms of 

the disease under continued treatment. In patients with wet AMD, DME, PDR and RVO, initially, 

three or more consecutive, monthly injections may be needed. 

 

Thereafter, monitoring and treatment intervals should be determined by the physician and should be 

based on disease activity, as assessed by visual acuity and/or anatomical parameters. 

 

If, in the physician’s opinion, visual and anatomical parameters indicate that the patient is not 

benefiting from continued treatment, Lucentis should be discontinued. 

 

Monitoring for disease activity may include clinical examination, functional testing or imaging 

techniques (e.g. optical coherence tomography or fluorescein angiography). 

 

If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is 

achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise 

until signs of disease activity or visual impairment recur. The treatment interval should be extended by 

no more than two weeks at a time for wet AMD and may be extended by up to one month at a time for 

DME. For PDR and RVO, treatment intervals may also be gradually extended, however there are 

insufficient data to conclude on the length of these intervals. If disease activity recurs, the treatment 

interval should be shortened accordingly. 

 

The treatment of visual impairment due to CNV should be determined individually per patient based 

on disease activity. Some patients may only need one injection during the first 12 months; others may 

need more frequent treatment, including a monthly injection. For CNV secondary to pathologic 

myopia (PM), many patients may only need one or two injections during the first year. 

 

Lucentis and laser photocoagulation in DME and macular oedema secondary to BRVO 

There is some experience of Lucentis administered concomitantly with laser photocoagulation. When 

given on the same day, Lucentis should be administered at least 30 minutes after laser 

photocoagulation. Lucentis can be administered in patients who have received previous laser 

photocoagulation. 

 

Lucentis and verteporfin photodynamic therapy in CNV secondary to PM 

There is no experience of concomitant administration of Lucentis and verteporfin. 

 

Lucentis should be inspected visually for particulate matter and discoloration prior to administration. 

 



78 

The injection procedure should be carried out under aseptic conditions, which includes the use of 

surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent) 

and the availability of sterile paracentesis (if required). The patient’s medical history for 

hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure. 

Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid 

and ocular surface should be administered prior to the injection, in accordance with local practice. 

 

Vial-only pack 

The vial is for single use only. After injection any unused product must be discarded. Any vial 

showing signs of damage or tampering must not be used. The sterility cannot be guaranteed unless the 

packaging seal remains intact. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G) 

- a 1 ml sterile syringe (including a 0.05 ml mark) 

- an injection needle (30G x ½″). 

These medical devices are not included within the Lucentis pack. 

 

Vial + filter needle pack 

All components are sterile and for single use only. Any component with packaging showing signs of 

damage or tampering must not be used. The sterility cannot be guaranteed unless the component 

packaging seal remains intact. Re-use may lead to infection or other illness/injury. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, provided) 

- a 1 ml sterile syringe (including a 0.05 ml mark, not included within the Lucentis pack) 

- an injection needle (30G x ½″; not included within the Lucentis pack) 

 

To prepare Lucentis for intravitreal administration to adult patients, please adhere to the following 

instructions: 

 

 

 
 

1. Before withdrawal, the outer part of the rubber stopper of 

the vial should be disinfected. 

 

2. Assemble a 5 µm filter needle (18G x 1½″, 

1.2 mm x 40 mm, 5 µm) onto a 1 ml syringe using aseptic 

technique. Push the blunt filter needle into the centre of the 

vial stopper until the needle touches the bottom edge of the 

vial. 

 

3. Withdraw all the liquid from the vial, keeping the vial in 

an upright position, slightly inclined to ease complete 

withdrawal. 

 

 
 

4. Ensure that the plunger rod is drawn sufficiently back 

when emptying the vial in order to completely empty the 

filter needle. 

 

5. Leave the blunt filter needle in the vial and disconnect 

the syringe from the blunt filter needle. The filter needle 

should be discarded after withdrawal of the vial contents 

and should not be used for the intravitreal injection. 



79 

 

 

6. Aseptically and firmly assemble an injection needle 

(30G x ½″, 0.3 mm x 13 mm) onto the syringe. 

 

7. Carefully remove the cap from the injection needle 

without disconnecting the injection needle from the syringe. 

 

Note: Grip at the hub of the injection needle while 

removing the cap. 

 

8. Carefully expel the air along with the excess solution 

from the syringe and adjust the dose to the 0.05 ml mark on 

the syringe. The syringe is ready for injection. 

 

Note: Do not wipe the injection needle. Do not pull back on 

the plunger. 

 

The injection needle should be inserted 3.5-4.0 mm posterior to the limbus into the vitreous cavity, 

avoiding the horizontal meridian and aiming towards the centre of the globe. The injection volume of 

0.05 ml is then delivered; a different scleral site should be used for subsequent injections. 

 

After injection, do not recap the needle or detach it from the syringe. Dispose of the used syringe 

together with the needle in a sharps disposal container or in accordance with local requirements. 

 

 

0.05 ml 



80 

Package leaflet: Information for the patient 

 

Lucentis 10 mg/ml solution for injection in pre-filled syringe 

ranibizumab 

 

 

Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor. 

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 

 

What is in this leaflet 
1. What Lucentis is and what it is used for 

2. What you need to know before you are given Lucentis 

3. How Lucentis is given 

4. Possible side effects 

5. How to store Lucentis 

6. Contents of the pack and other information 

 

 

1. What Lucentis is and what it is used for 

 

What Lucentis is 

Lucentis is a solution which is injected into the eye. Lucentis belongs to a group of medicines called 

antineovascularisation agents. It contains the active substance called ranibizumab. 

 

What Lucentis is used for 

Lucentis is used in adults to treat several eye diseases causing vision impairment. 

 

These diseases result from damage to the retina (light-sensitive layer at the back of the eye) caused by: 

- Growth of leaky, abnormal blood vessels. This is observed in diseases such as age-related 

macular degeneration (AMD) and proliferative diabetic retinopathy (PDR, a disease caused by 

diabetes). It may also be associated with choroidal neovascularisation (CNV) due to pathologic 

myopia (PM), angioid streaks, central serous chorioretinopathy or inflammatory CNV. 

- Macular oedema (swelling of the centre of the retina). This swelling can be caused by diabetes 

(a disease called diabetic macular oedema (DME)) or by the blockage of retinal veins of the 

retina (a disease called retinal vein occlusion (RVO)). 

 

How Lucentis works 

Lucentis specifically recognises and binds to a protein called human vascular endothelial growth 

factor A (VEGF-A) present in the eye. In excess, VEGF-A causes abnormal blood vessel growth and 

swelling in the eye which can lead to impairment of vision in diseases like AMD, DME, PDR, RVO, 

PM and CNV. By binding to VEGF-A, Lucentis can block its actions and prevent this abnormal 

growth and swelling. 

 

In these diseases, Lucentis can help to stabilise and in many cases improve your vision. 

 

 

  



81 

2. What you need to know before you are given Lucentis 

 

You must not receive Lucentis 

- If you are allergic to ranibizumab or any of the other ingredients of this medicine (listed in 

section 6). 

- If you have an infection in or around your eye. 

- If you have pain or redness (severe intraocular inflammation) in your eye. 

 

Warnings and precautions 

Talk to your doctor before you are given Lucentis. 

- Lucentis is given as an injection into the eye. Occasionally, an infection in the internal portion 

of the eye, pain or redness (inflammation), detachment or tear of one of the layers in the back of 

the eye (retinal detachment or tear and retinal pigment epithelial detachment or tear), or 

clouding of the lens (cataract) may occur after Lucentis treatment. It is important to identify and 

treat such an infection or retinal detachment as soon as possible. Please tell your doctor 

immediately if you develop signs such as eye pain or increased discomfort, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in your vision or 

increased sensitivity to light. 

- In some patients the eye pressure may increase for a short period directly after the injection. 

This is something you may not notice, therefore your doctor may monitor this after each 

injection. 

- Inform your doctor if you have a prior history of eye conditions or eye treatments, or if you 

have had a stroke or experienced transient signs of stroke (weakness or paralysis of limbs or 

face, difficulty speaking or understanding). This information will be taken into account to 

evaluate if Lucentis is the appropriate treatment for you. 

 

Please see section 4 (“Possible side effects”) for more detailed information on side effects that could 

occur during Lucentis therapy. 

 

Children and adolescents (below 18 years of age) 

The use of Lucentis in children and adolescents has not been established and is therefore not 

recommended. 

 

Other medicines and Lucentis 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding 
- Women who could become pregnant must use effective contraception during treatment and for 

at least three further months after the last injection of Lucentis. 

- There is no experience of using Lucentis in pregnant women. Lucentis should not be used 
during pregnancy unless the potential benefit outweighs the potential risk to the unborn child. If 

you are pregnant, think you may be pregnant or planning to become pregnant, discuss this with 

your doctor before treatment with Lucentis. 

- Lucentis is not recommended during breast-feeding because it is not known whether Lucentis 
passes into human milk. Ask your doctor or pharmacist for advice before Lucentis treatment. 

 

Driving and using machines 

After Lucentis treatment you may experience some temporary vision blurring. If this happens, do not 

drive or use machines until this resolves. 

 

 



82 

3. How Lucentis is given 

 

Lucentis is administered as a single injection into your eye by your eye doctor under a local 

anaesthetic. The usual dose of an injection is 0.05 ml (which contains 0.5 mg of active substance). The 

pre-filled syringe contains more than the recommended dose of 0.5 mg. The extractable volume is not 

to be used in total. The excess volume should be expelled prior to injection. Injecting the entire 

volume of the pre-filled syringe could result in overdose. 

 

The interval between two doses injected into the same eye should be at least four weeks. All injections 

will be administered by your eye doctor. 

 

Before the injection, your doctor will wash your eye carefully to prevent infection. Your doctor will 

also give you a local anaesthetic to reduce or prevent any pain you might have with the injection. 

 

The treatment is started with one injection of Lucentis per month. Your doctor will monitor the 

condition of your eye and, depending on how you respond to the treatment, will decide if and when 

you need to receive further treatment. 

 

Detailed instructions for use are given at the end of the leaflet under “How to prepare and administer 

Lucentis”. 

 

Elderly (age 65 years and over) 

Lucentis can be used for people of 65 years of age and over without dose adjustment. 

 

Before stopping Lucentis treatment 

If you are considering stopping Lucentis treatment, please go to your next appointment and discuss 

this with your doctor. Your doctor will advise you and decide how long you should be treated with 

Lucentis. 

 

If you have any further questions on the use of this medicine, ask your doctor. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The side effects associated with the administration of Lucentis are either due to the medicine itself or 

the injection procedure and mostly affect the eye. 

 

The most serious side effects are described below: 

Common serious side effects (may affect up to 1 in 10 people): Detachment or tear of the layer in the 

back of the eye (retinal detachment or tear), resulting in flashes of light with floaters progressing to a 

temporary loss of sight, or a clouding of the lens (cataract). 

Uncommon serious side effects (may affect up to 1 in 100 people): Blindness, infection of the eyeball 

(endophthalmitis) with inflammation of the inside of the eye. 

 

The symptoms you might experience are pain or increased discomfort in your eye, worsening eye 

redness, blurred or decreased vision, an increased number of small particles in your vision or increased 

sensitivity to light. Please tell your doctor immediately if you develop any of these side effects. 

 

The most frequently reported side effects are described below: 

Very common side effects (may affect more than 1 in 10 people) 

Visual side effects include: Inflammation of the eye, bleeding in the back of the eye (retinal bleeding), 

visual disturbances, eye pain, small particles or spots in your vision (floaters), bloodshot eye, eye 

irritation, a feeling of having something in the eye, increased tear production, inflammation or 

infection of the eyelid margins, dry eye, redness or itching of the eye and increased eye pressure. 

Non-visual side effects include: Sore throat, nasal congestion, runny nose, headache and joint pain. 



83 

 

Other side effects which may occur following Lucentis treatment are described below: 

Common side effects 
Visual side effects include: Decreased sharpness of vision, swelling of a section of the eye (uvea, 

cornea), inflammation of the cornea (front part of eye), small marks on the surface of the eye, blurred 

vision, bleeding at the site of injection, bleeding in the eye, discharge from the eye with itching, 

redness and swelling (conjunctivitis), light sensitivity, eye discomfort, swelling of the eyelid, eyelid 

pain. 

Non-visual side effects include: Urinary tract infection, low red blood cells count (with symptoms 

such as tiredness, breathlessness, dizziness, pale skin), anxiety, cough, nausea, allergic reactions like 

rash, hives, itching and skin reddening. 

 

Uncommon side effects 
Visual side effects include: Inflammation and bleeding in the front part of the eye, sac of pus on the 

eye, changes of the central part of the eye surface, pain or irritation at the site of injection, abnormal 

sensation in the eye, irritation of the eyelid. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 

leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 

By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Lucentis 
 

- Keep this medicine out of the sight and reach of children. 

- Do not use this medicine after the expiry date which is stated on the carton and pre-filled 
syringe label after EXP. The expiry date refers to the last day of that month. 

- Store in a refrigerator (2°C – 8°C). Do not freeze. 

- Prior to use, the sealed tray may be kept at room temperature (25°C) for up to 24 hours. 
- Keep the pre-filled syringe in its unopened tray in the carton in order to protect from light. 

- Do not use any pack that is damaged. 

 

 

6. Contents of the pack and other information 

 

What Lucentis contains 

- The active substance is ranibizumab. Each ml contains 10 mg ranibizumab. One pre-filled 

syringe contains 0.165 ml, equivalent to 1.65 mg ranibizumab. This provides a usable amount to 

deliver a single dose of 0.05 ml containing 0.5 mg ranibizumab. 

- The other ingredients are α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; 

histidine; polysorbate 20; water for injections. 

 

What Lucentis looks like and contents of the pack 

Lucentis is a solution for injection in a pre-filled syringe. The pre-filled syringe contains 0.165 ml of a 

sterile, clear, colourless to pale yellow aqueous solution. The pre-filled syringe contains more than the 

recommended dose of 0.5 mg. The extractable volume is not to be used in total. The excess volume 

should be expelled prior to injection. Injecting the entire volume of the pre-filled syringe could result 

in overdose. 

 

Pack size of one pre-filled syringe, packed in a sealed tray. The pre-filled syringe is for single use 

only. 

 



84 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Alcon Couvreur NV 

Rijksweg 14 

2870 Puurs 

Belgium 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 



85 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 



86 

The following information is intended for healthcare professionals only: 

 

Please also refer to section 3 “How Lucentis is given”. 

 

How to prepare and administer Lucentis 

 

Single-use pre-filled syringe for intravitreal use only 

 

Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections. 

 

In wet AMD, in CNV, in PDR and in visual impairment due to DME or to macular oedema secondary 

to RVO the recommended dose for Lucentis is 0.5 mg given as a single intravitreal injection. This 

corresponds to an injection volume of 0.05 ml. The interval between two doses injected into the same 

eye should be at least four weeks. 

 

Treatment is initiated with one injection per month until maximum visual acuity is achieved and/or 

there are no signs of disease activity i.e. no change in visual acuity and in other signs and symptoms of 

the disease under continued treatment. In patients with wet AMD, DME, PDR and RVO, initially, 

three or more consecutive, monthly injections may be needed. 

 

Thereafter, monitoring and treatment intervals should be determined by the physician and should be 

based on disease activity, as assessed by visual acuity and/or anatomical parameters. 

 

If, in the physician’s opinion, visual and anatomical parameters indicate that the patient is not 

benefiting from continued treatment, Lucentis should be discontinued. 

 

Monitoring for disease activity may include clinical examination, functional testing or imaging 

techniques (e.g. optical coherence tomography or fluorescein angiography). 

 

If patients are being treated according to a treat-and-extend regimen, once maximum visual acuity is 

achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise 

until signs of disease activity or visual impairment recur. The treatment interval should be extended by 

no more than two weeks at a time for wet AMD and may be extended by up to one month at a time for 

DME. For PDR and RVO, treatment intervals may also be gradually extended, however there are 

insufficient data to conclude on the length of these intervals. If disease activity recurs, the treatment 

interval should be shortened accordingly. 

 

The treatment of visual impairment due to CNV should be determined individually per patient based 

on disease activity. Some patients may only need one injection during the first 12 months; others may 

need more frequent treatment, including a monthly injection. For CNV secondary to pathologic 

myopia (PM), many patients may only need one or two injections during the first year. 

 

Lucentis and laser photocoagulation in DME and macular oedema secondary to BRVO 

There is some experience of Lucentis administered concomitantly with laser photocoagulation. When 

given on the same day, Lucentis should be administered at least 30 minutes after laser 

photocoagulation. Lucentis can be administered in patients who have received previous laser 

photocoagulation. 

 

Lucentis and verteporfin photodynamic therapy in CNV secondary to PM 

There is no experience of concomitant administration of Lucentis and verteporfin. 

 

Lucentis should be inspected visually for particulate matter and discoloration prior to administration. 

 

The injection procedure should be carried out under aseptic conditions, which includes the use of 

surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent) 

and the availability of sterile paracentesis (if required). The patient’s medical history for 

hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure. 



87 

Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid 

and ocular surface should be administered prior to the injection, in accordance with local practice. 

 

The pre-filled syringe is for single use only. The pre-filled syringe is sterile. Do not use the product if 

the packaging is damaged. The sterility of the pre-filled syringe cannot be guaranteed unless the tray 

remains sealed. Do not use the pre-filled syringe if the solution is discoloured, cloudy or contains 

particles. 

 

The pre-filled syringe contains more than the recommended dose of 0.5 mg. The extractable volume of 

the pre-filled syringe (0.1 ml) is not to be used in total. The excess volume should be expelled prior to 

injection. Injecting the entire volume of the pre-filled syringe could result in overdose. To expel the air 

bubble along with the excess medicinal product, slowly push the plunger until the edge below the 

dome of the rubber stopper is aligned with the black dosing line on the syringe (equivalent to 0.05 ml, 

i.e., 0.5 mg ranibizumab). 

 

For the intravitreal injection, a 30G x ½″ sterile injection needle should be used. 

 

To prepare Lucentis for intravitreal administration, please adhere to the instructions for use: 

 

Introduction Read all the instructions carefully before using the pre-filled syringe. 

The pre-filled syringe is for single use only. The pre-filled syringe is sterile. Do 

not use the product if the packaging is damaged. The opening of the sealed tray 

and all subsequent steps should be done under aseptic conditions. 

Note: The dose must be set to 0.05 ml. 

Pre-filled 

syringe 

description 

 

 

 

 

 

Prepare 1. Make sure that the pack contains: 

 a sterile pre-filled syringe in a sealed tray. 
2. Peel the lid off the syringe tray and, using aseptic technique, carefully 

remove the syringe. 

Check syringe 3. Check that: 

 the syringe cap is not detached from the 
Luer lock. 

 the syringe is not damaged. 

 the solution looks clear, colourless to pale 
yellow and does not contain any particles. 

4. If any of the above is not true, discard the 

pre-filled syringe and use a new one. 

 

Syringe cap 0.05 ml dose mark Finger grip 

Plunger rod Rubber stopper Luer lock 

Figure 1 



88 

Remove 

syringe cap 

5. Snap off (do not turn or twist) the syringe 

cap (see Figure 2). 

6. Dispose of the syringe cap (see Figure 3). 

 
Figure 2 

 

 
Figure 3 

Attach needle 7. Attach a 30G x ½″ sterile injection needle 

firmly onto the syringe by screwing it 

tightly onto the Luer lock (see Figure 4). 

8. Carefully remove the needle cap by 

pulling it straight off (see Figure 5). 

Note: Do not wipe the needle at any time. 

 

Figure 4 Figure 5 



89 

Dislodge air 

bubbles 

9. Hold the syringe upright. 

10. If there are any air bubbles, gently tap the 

syringe with your finger until the bubbles 

rise to the top (see Figure 6). 

 

 
Figure 6 

 

Set dose 11. Hold the syringe at eye level and 

carefully push the plunger until the edge 

below the dome of the rubber stopper 
is aligned with the dose mark (see 

Figure 7). This will expel the air and the 

excess solution and set the dose to 

0.05 ml. 

Note: The plunger rod is not attached to the 

rubber stopper – this is to prevent air being 

drawn into the syringe. 

 

 
Figure 7 

Inject The injection procedure should be carried out under aseptic conditions. 

12. The injection needle should be inserted 3.5-4.0 mm posterior to the limbus 

into the vitreous cavity, avoiding the horizontal meridian and aiming towards 

the centre of the globe. 

13. Inject slowly until the rubber stopper reaches the bottom of the syringe to 

deliver the volume of 0.05 ml. 

14. A different scleral site should be used for subsequent injections. 

15. After injection, do not recap the needle or detach it from the syringe. Dispose 

of the used syringe together with the needle in a sharps disposal container or 

in accordance with local requirements. 

 



90 

Package leaflet: Information for guardians of babies born prematurely 

 

Lucentis 10 mg/ml solution for injection 

ranibizumab 

 

BABIES BORN PREMATURELY 

 

Please find information for adults on the other side of this leaflet. 

 

Read all of this leaflet carefully before your baby is given this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your baby’s doctor. 

- If your baby gets any side effects, talk to your baby’s doctor. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 
1. What Lucentis is and what it is used for 

2. What you need to know before your baby is given Lucentis 

3. How Lucentis is given 

4. Possible side effects 

5. How to store Lucentis 

6. Contents of the pack and other information 

 

 

1. What Lucentis is and what it is used for 

 

What Lucentis is 

Lucentis is a solution which is injected into the eye. Lucentis belongs to a group of medicines called 

antineovascularisation agents. It contains the active substance called ranibizumab. 

 

What Lucentis is used for 
Lucentis is used in babies born prematurely to treat retinopathy of prematurity (ROP), a disease 

causing vision impairment due to damage to the back of the eye (the retina) caused by abnormal 

growth of blood vessels. 

 

How Lucentis works 

Lucentis specifically recognises and binds to a protein called human vascular endothelial growth 

factor A (VEGF-A) present in the eye. In excess, VEGF-A causes abnormal blood vessel growth in the 

eye. Lucentis can block its actions and prevent this abnormal growth. 

 

 

2. What you need to know before your baby is given Lucentis 

 

Your baby must not receive Lucentis 

- If your baby is allergic to ranibizumab or any of the other ingredients of this medicine (listed in 

section 6). 

- If your baby has an infection in or around the eye. 

- If your baby has pain or redness (severe intraocular inflammation) in the eye. 

 

  



91 

Warnings and precautions 

Talk to your baby’s doctor before your baby is given Lucentis. 

- Lucentis is given as an injection into the eye. Occasionally, an infection in the internal portion 

of the eye, pain or redness (inflammation), detachment or tear of one of the layers in the back of 

the eye (retinal detachment or tear and retinal pigment epithelial detachment or tear), or 

clouding of the lens (cataract) may occur after Lucentis treatment. It is important to identify and 

treat such an infection or retinal detachment as soon as possible. Please tell the doctor 

immediately if your baby develops signs such as eye pain or worsening eye redness. 
- In some patients the eye pressure may increase for a short period directly after the injection. 

Your baby’s doctor may monitor this after each injection. 

 

Please see section 4 (“Possible side effects”) for more detailed information on side effects that could 

occur during Lucentis therapy. 

 

Other medicines and Lucentis 

Tell your baby’s doctor if your baby is receiving, has recently received or might receive any other 

medicines. 

 

 

3. How Lucentis is given 

 

Lucentis will be administered by an eye doctor as a single injection into your baby’s eyes, usually 

under local anaesthetic. The usual dose of an injection is 0.02 ml (which contains 0.2 mg of active 

substance). The interval between two doses injected into the same eye should be at least four weeks. 

All injections will be administered by the eye doctor. 

 

Before the injection, your baby’s doctor will wash your baby’s eyes carefully to prevent infection. The 

doctor will also give your baby a local anaesthetic to reduce or prevent any pain. 

 

The treatment is started with one injection of Lucentis in each eye (some babies may only need 

treatment in one eye). The doctor will monitor the condition of your baby’s eye(s) and, depending on 

how your baby responds to the treatment, will decide if and when further treatment is needed. 

 

Detailed instructions for use are given at the end of the leaflet under “How to prepare and administer 

Lucentis”. 

 

Before stopping Lucentis treatment 

If you are considering stopping Lucentis treatment for your baby, please go to your next appointment 

and discuss this with your baby’s doctor. Your baby’s doctor will advise you and decide how long 

your baby should be treated with Lucentis. 

 

If you have any further questions on the use of this medicine, ask your baby’s doctor. 

 

 

  



92 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The side effects associated with the administration of Lucentis are due either to the medicine itself or 

to the injection procedure and mostly affect the eye. 

 

The most common side effects in babies born prematurely are described below: 

 

Visual side effects include: Bleeding in the back of the eye (retinal bleeding), bleeding in the eye or at 

the site of injection, and bloodshot eye (conjunctival bleeding). 

 

Non-visual side effects include: Sore throat, nasal congestion and runny nose, low red blood cell 

counts (with symptoms such as tiredness, breathlessness, pale skin), cough, urinary tract infection, 

allergic reactions like rash and skin reddening. 

 

Additional side effects that have been observed with Lucentis in adults are listed below. These 

side effects may also occur in babies born prematurely. 

 

The most serious side effects in adults are described below: 

Common serious side effects (may affect up to 1 in 10 people): Detachment or tear of the layer in the 

back of the eye (retinal detachment or tear) progressing to a temporary loss of sight, or a clouding of 

the lens (cataract). 

Uncommon serious side effects (may affect up to 1 in 100 people): Blindness, infection of the eyeball 

(endophthalmitis) with inflammation of the inside of the eye. 

 

It is important to identify and treat serious side effects such as infection of the eyeball or retinal 

detachment as soon as possible. Please tell the doctor immediately if your baby develops signs 

such as eye pain or worsening eye redness. 

 

Other side effects in adults are described below: 

Very common side effects (may affect more than 1 in 10 people) 

Visual side effects include: Inflammation of the eye, visual disturbances, eye pain, small particles or 

spots in your vision (floaters), eye irritation, a feeling of having something in the eye, increased tear 

production, inflammation or infection of the eyelid margins, dry eye, redness or itching of the eye and 

increased eye pressure. 

Non-visual side effects include: Headache and joint pain. 

 

Common side effects 

Visual side effects include: Decreased sharpness of vision, swelling of a section of the eye (uvea, 

cornea), inflammation of the cornea (front part of eye), small marks on the surface of the eye, blurred 

vision, discharge from the eye with itching, redness and swelling (conjunctivitis), light sensitivity, eye 

discomfort, swelling of the eyelid, eyelid pain. 

Non-visual side effects include: Anxiety, nausea. 

 

Uncommon side effects 

Visual side effects include: Inflammation and bleeding in the front part of the eye, sac of pus on the 

eye, changes of the central part of the eye surface, pain or irritation at the site of injection, abnormal 

sensation in the eye, irritation of the eyelid. 
 

If you have any questions about any side effects, ask your baby’s doctor. 

 



93 

Reporting of side effects 

If you observe any side effects in your baby, talk to your baby`s doctor. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Lucentis 
 

- Keep this medicine out of the sight and reach of children. 

- Do not use this medicine after the expiry date which is stated on the carton and vial label after 
EXP. The expiry date refers to the last day of that month. 

- Store in a refrigerator (2°C – 8°C). Do not freeze. 

- Prior to use, the unopened vial may be kept at room temperature (25°C) for up to 24 hours. 

- Keep the vial in the outer carton in order to protect from light. 

- Do not use any pack that is damaged. 

 

 

6. Contents of the pack and other information 

 

What Lucentis contains 

- The active substance is ranibizumab. Each ml contains 10 mg ranibizumab. Each vial contains 

2.3 mg ranibizumab in 0.23 ml solution. This provides a suitable amount to deliver a single dose 

of 0.02 ml containing 0.2 mg ranibizumab. 

- The other ingredients are α,α-trehalose dihydrate; histidine hydrochloride, monohydrate; 

histidine; polysorbate 20; water for injections. 

 

What Lucentis looks like and contents of the pack 

Lucentis is a solution for injection in a vial (0.23 ml). The solution is clear, colourless to pale yellow 

and aqueous. 

 

Two different pack types are available: 

 

Vial-only pack 

Pack containing one glass vial of ranibizumab with chlorobutyl rubber stopper. The vial is for single 

use only. 

 

Vial + filter needle pack 

Pack containing one glass vial of ranibizumab with chlorobutyl rubber stopper and one blunt filter 

needle (18G x 1½″, 1.2 mm x 40 mm, 5 micrometres) for withdrawal of the vial contents. All 

components are for single use only. 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 



94 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA „Novartis Baltics“ Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



95 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 



96 

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE 

PROFESSIONALS ONLY: 

 

Please also refer to section 3 “How Lucentis is given”. 

 

How to prepare and administer Lucentis to preterm infants 

 

Single-use vial for intravitreal use only. 

 

Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections in 

preterm infants. 

 

For treatment of preterm infants use the low volume high accuracy syringe provided together 

with an injection needle (30G x ½″) in the VISISURE kit. 
 

For preterm infants the recommended dose for Lucentis is 0.2 mg given as a single intravitreal 

injection. This corresponds to an injection volume of 0.02 ml. In preterm infants treatment of 

retinopathy of prematurity (ROP) is initiated with a single injection per eye and may be given 

bilaterally on the same day. In total up to three injections per eye may be administered within six 

months of treatment initiation if there are signs of disease activity. Most patients (78%) in the 

conducted clinical study received one injection per eye. The administration of more than three 

injections per eye has not been studied. The interval between two doses injected into the same eye 

should be at least four weeks. 

 

Lucentis should be inspected visually for particulate matter and discoloration prior to administration. 

 

The injection procedure should be carried out under aseptic conditions, which includes the use of 

surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent) 

and the availability of sterile paracentesis (if required). The patient’s medical history for 

hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure. 

Adequate anaesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid 

and ocular surface should be administered prior to the injection, in accordance with local practice. 

 

Vial-only pack 

The vial is for single use only. After injection any unused product must be discarded. Any vial 

showing signs of damage or tampering must not be used. The sterility cannot be guaranteed unless the 

packaging seal remains intact. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G); not included within the Lucentis pack 

- a low volume high accuracy sterile syringe (supplied separately inside the VISISURE kit) 

- an injection needle (30G x ½″); (supplied separately inside the VISISURE kit) 

 

  



97 

Vial + filter needle pack 

All components are sterile and for single use only. Any component with packaging showing signs of 

damage or tampering must not be used. The sterility cannot be guaranteed unless the component 

packaging seal remains intact. Re-use may lead to infection or other illness/injury. 

 

For preparation and intravitreal injection the following medical devices for single use are needed: 

- a 5 µm filter needle (18G x 1½″, 1.2 mm x 40 mm, provided) 

- a low volume high accuracy sterile syringe (supplied separately inside the VISISURE kit) 

- an injection needle (30G x ½″) (supplied separately inside the VISISURE kit) 

 

To prepare Lucentis for intravitreal administration to preterm infants please adhere to the instructions 

for use in the VISISURE kit. 

 

The injection needle should be inserted into the eye 1.0 to 2.0 mm posterior to the limbus, with the 

needle pointing towards the optic nerve. The injection volume of 0.02 ml is then delivered. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET