Adverse reactions : תופעות לוואי

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 studies 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


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 studies 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 study (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 hemorrhage and conjunctival hemorrhage. Non-ocular adverse reactions reported in more than one patient treated with ranibizumab 0.2 mg were nasopharyngitis, anemia, 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 study.

Long-term safety in preterm infants with ROP has been studied up to the age of five years old in the RAINBOW extension study and showed no new safety signals. The safety profile of ranibizumab 0.2 mg during the extension study was consistent with that observed in the core study at 24 weeks.

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.
Any suspected adverse event should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il