Lucentis Adverse Reactions

Summary of the safety profile: Wet AMD population: A total of 1,315 patients constituted the safety population in the three controlled phase III studies for wet AMD (FVF2598g (MARINA), FVF2587g (ANCHOR) and FVF3192g (PIER)) with 24 months exposure to Lucentis and 440 patients were treated with the recommended dose of 0.5 mg.
Serious adverse events related to the injection procedure included endophthalmitis, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract (see Precautions).
Other serious ocular events observed among Lucentis-treated patients included intraocular inflammation and increased intraocular pressure (see Precautions).
The adverse events listed as follows in Table 16 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 injection, as defined in Pharmacology: Pharmacodynamics under Actions or verteporfin photodynamic therapy (PDT)) in the pooled data of the three controlled wet AMD studies. These were therefore considered potential adverse drug reactions. The safety data described as follows also include all adverse events suspected to be at least potentially related to the injection procedure or medicinal product in the 440 wAMD patients treated with 0.5 mg Lucentis.
DME population: The safety of Lucentis was studied in a one-year sham-controlled trial (RESOLVE) and in a one-year laser-controlled trial (RESTORE) conducted respectively in 102 and 235 ranibizumab-treated patients with visual impairment due to DME (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The event of urinary tract infection, in the common frequency category, met the adverse reaction criteria for the Table 16 as follows; otherwise ocular and non-ocular events in the RESOLVE and RESTORE trials were reported with a frequency and severity similar to those seen in the wet AMD trials.
DR population: The safety of Lucentis was studied for up to 24-months in Protocol S and the clinical trials RESTORE, REVEAL, and REFINE, including 395 ranibizumab-treated patients with moderately severe to severe NPDR or PDR (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Ocular and non-ocular events observed were consistent with what would be expected in a diabetic patient population with DR, or have been reported with a frequency and severity similar to those seen in previous clinical trials with Lucentis.
RVO population: The safety of Lucentis was studied in two 12-month trials (BRAVO and CRUISE) conducted respectively in 264 and 261 ranibizumab-treated patients with visual impairment due to macular edema secondary to BRVO and CRVO, respectively (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Ocular and non-ocular events in the BRAVO and CRUISE trials were reported with a frequency and severity similar to those seen in the wet-AMD trials.
CNV population: The safety of Lucentis was studied in a 12-month clinical trial (MINERVA), which included 171 ranibizumab-treated patients with visual impairment due to CNV (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The safety profile in these patients was consistent with that seen in previous clinical trials with Lucentis.
PM population: The safety of Lucentis was studied in the 12-month clinical trial (RADIANCE), which included 224 ranibizumab-treated patients with visual impairment due to CNV secondary to PM (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Ocular and non-ocular events in this trial were reported with a frequency and severity similar to those seen in the wet-AMD trials.
Tabulated summary of adverse drug reactions from clinical trials: The adverse drug reactions from clinical trials (Table 16) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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). (See Table 16.)

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A meta-analysis of pooled safety data from completed, randomized, double masked global studies showed a higher incidence rate of non-serious, non-ocular wound infection/inflammation in DME patients treated with ranibizumab 0.5 mg (1.85/100 patient years) compared to control (0.27/100 patient years). The relationship to ranibizumab remains unknown.
Retinopathy of Prematurity (ROP) population: The safety of Lucentis 0.2 mg was studied in the 6-month clinical trial (RAINBOW), which included 73 ranibizumab-treated preterm infants with ROP (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Ocular events observed in the RAINBOW trial were consistent with those seen in adults treated with ranibizumab 0.5 mg. In general, the non-ocular events in this trial were consistent with what would be expected for this patient population with multiple comorbidities due to prematurity.
Long-term safety in preterm infants with ROP has been established up to the age of five years in the RAINBOW extension study and showed no new safety signals. The safety profile of ranibizumab 0.2 mg during the RAINBOW extension study was consistent with that observed in the RAINBOW core study at 24 weeks.