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Indications/Uses
Ranibizumab (Lucentis) is indicated in adults for: treatment of neovascular (wet) age-related macular degeneration (AMD); treatment of proliferative diabetic retinopathy (PDR); treatment of visual impairment due to choroidal neovascularization (CNV); treatment of visual impairment due to choroidal neovascularization (CNV) secondary to pathologic myopia (PM); treatment of visual impairment due to diabetic macular edema (DME); treatment of visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO).
Ranibizumab (Lucentis) is indicated in preterm infants for: treatment of retinopathy of prematurity (ROP) (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Ranibizumab (Lucentis) is indicated in preterm infants for: treatment of retinopathy of prematurity (ROP) (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Dosage/Direction for Use
Dosage regimen: Single-use vial (adults and preterm infants) for intravitreal use only. Use of more than one injection from a vial can lead to product contamination and subsequent ocular infection.
Ranibizumab (Lucentis) must be administered by a qualified ophthalmologist experienced in intravitreal injections.
The recommended dose 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 in to the same eye should not be shorter than one month.
The recommended dose for ranibizumab (Lucentis) in preterm infants is 0.2 mg given as a single intravitreal injection. This corresponds to an injection volume of 0.02 mL. Treatment of ROP is initiated with a single dose & can be given bilaterally on the same day. Further treatment may be administered if there are signs of disease activity. The interval between two doses injected into the same eye should not be shorter than one month.
General target population: Treatment of wet AMD, DME, PDR, macular edema secondary to RVO, CNV, or CNV secondary to PM: 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.
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 anatomic parameters.
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, for example, the treatment intervals can be extended stepwise until signs of disease activity or visual impairment recur. The treatment interval should be extended by two weeks at a time for wet AMD and central RVO (CRVO), or by one month at a time for DME and branch RVO (BRVO). 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. In the treatment of visual impairment due to CNV secondary to PM, many patients may only need one or two injections during the first year, while some patients may need more frequent treatment (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Concomitant Use with Laser Photocoagulation in DME and branch RVO: Ranibizumab (Lucentis) has been used concomitantly with laser photocoagulation in clinical studies (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). When given on the same day, it should be administered at least 30 minutes after laser photocoagulation. The drug product can be administered in patients who have received previous laser photocoagulation.
Treatment of ROP in preterm infants: Treatment in preterm infants is initiated with a single injection. Further treatment may be administered if there are signs of disease activity.
Special populations: Hepatic impairment: There are no studies in patients with hepatic impairment. However, as systemic exposure is negligible, no special measures are considered necessary in this population.
Renal impairment: Dose adjustment is not needed in patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Pediatric patients (below 18 years): Not recommended for use in children and adolescents due to insufficient data on safety and efficacy in these sub-populations. Limited data on adolescent patients aged 12 to 17 years with visual impairment due to CNV is available (see Pharmacology: Pharmacodynamics: Clinical Studies: Pediatric patients under Actions).
Geriatric patients (65 years and above): No dose adjustment is required in the elderly.
Method of administration: As with all medicinal products for parenteral use, ranibizumab (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). Sterile paracentesis equipment should be available as a precautionary measure. The patient's medical history for hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure (see Contraindications). Adequate anesthesia and a broad-spectrum topical to disinfect the periocular skin, eyelid and ocular surface microbicide should be administered prior to the injection.
For information on preparation of ranibizumab (Lucentis), see Instructions for Use and Handling under Cautions for Usage.
In adults, the injection needle should be inserted 3.5 to 4.0 mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and aiming towards the center of the globe. The injection volume of 0.05 mL is then delivered; the scleral site should be rotated for subsequent injections.
In preterm infants, the injection needle should be inserted 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.
Ranibizumab (Lucentis) must be administered by a qualified ophthalmologist experienced in intravitreal injections.
The recommended dose 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 in to the same eye should not be shorter than one month.
The recommended dose for ranibizumab (Lucentis) in preterm infants is 0.2 mg given as a single intravitreal injection. This corresponds to an injection volume of 0.02 mL. Treatment of ROP is initiated with a single dose & can be given bilaterally on the same day. Further treatment may be administered if there are signs of disease activity. The interval between two doses injected into the same eye should not be shorter than one month.
General target population: Treatment of wet AMD, DME, PDR, macular edema secondary to RVO, CNV, or CNV secondary to PM: 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.
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 anatomic parameters.
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, for example, the treatment intervals can be extended stepwise until signs of disease activity or visual impairment recur. The treatment interval should be extended by two weeks at a time for wet AMD and central RVO (CRVO), or by one month at a time for DME and branch RVO (BRVO). 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. In the treatment of visual impairment due to CNV secondary to PM, many patients may only need one or two injections during the first year, while some patients may need more frequent treatment (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Concomitant Use with Laser Photocoagulation in DME and branch RVO: Ranibizumab (Lucentis) has been used concomitantly with laser photocoagulation in clinical studies (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). When given on the same day, it should be administered at least 30 minutes after laser photocoagulation. The drug product can be administered in patients who have received previous laser photocoagulation.
Treatment of ROP in preterm infants: Treatment in preterm infants is initiated with a single injection. Further treatment may be administered if there are signs of disease activity.
Special populations: Hepatic impairment: There are no studies in patients with hepatic impairment. However, as systemic exposure is negligible, no special measures are considered necessary in this population.
Renal impairment: Dose adjustment is not needed in patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Pediatric patients (below 18 years): Not recommended for use in children and adolescents due to insufficient data on safety and efficacy in these sub-populations. Limited data on adolescent patients aged 12 to 17 years with visual impairment due to CNV is available (see Pharmacology: Pharmacodynamics: Clinical Studies: Pediatric patients under Actions).
Geriatric patients (65 years and above): No dose adjustment is required in the elderly.
Method of administration: As with all medicinal products for parenteral use, ranibizumab (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). Sterile paracentesis equipment should be available as a precautionary measure. The patient's medical history for hypersensitivity reactions should be carefully evaluated prior to performing the intravitreal procedure (see Contraindications). Adequate anesthesia and a broad-spectrum topical to disinfect the periocular skin, eyelid and ocular surface microbicide should be administered prior to the injection.
For information on preparation of ranibizumab (Lucentis), see Instructions for Use and Handling under Cautions for Usage.
In adults, the injection needle should be inserted 3.5 to 4.0 mm posterior to the limbus into the vitreous cavity, avoiding the horizontal meridian and aiming towards the center of the globe. The injection volume of 0.05 mL is then delivered; the scleral site should be rotated for subsequent injections.
In preterm infants, the injection needle should be inserted 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.
Overdosage
Cases of accidental overdose (injection of volumes greater than the recommended 0.05 mL dose) have been reported from the clinical studies in wet AMD and post-marketing data. Adverse reactions most frequently associated with these reported cases were increased intraocular pressure and eye pain. If an overdose occurs, intraocular pressure should be monitored and treated, if deemed necessary by the attending physician.
In clinical trials doses up to 2 mg of ranibizumab in an injection volume of 0.05 mL to 0.10 mL have been administered to patients with wet AMD and DME. The type and frequency of ocular and systemic adverse events were consistent with those reported for the 0.5 mg (in 0.05 mL) ranibizumab (Lucentis) dose.
In clinical trials doses up to 2 mg of ranibizumab in an injection volume of 0.05 mL to 0.10 mL have been administered to patients with wet AMD and DME. The type and frequency of ocular and systemic adverse events were consistent with those reported for the 0.5 mg (in 0.05 mL) ranibizumab (Lucentis) dose.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Patients with active or suspected ocular or periocular infections.
Patients with active intraocular inflammation.
Patients with active or suspected ocular or periocular infections.
Patients with active intraocular inflammation.
Special Precautions
Intravitreal injection-related reactions: Intravitreal injections, including those with ranibizumab (Lucentis), have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract (see Adverse Reactions). Proper aseptic injection techniques must always be used during administration. 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 previously mentioned events without delay.
In adults, transient increases in intraocular pressure (IOP) have been seen within 60 minutes of injection (see Adverse Reactions). Sustained IOP increases have also been reported. Both intraocular pressure and perfusion of the optic nerve head must be monitored and managed appropriately.
Arterial thromboembolic events: There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF (vascular endothelial growth factor) inhibitors. In the wet AMD Phase III studies, the overall frequency of arterial thromboembolic events was similar between ranibizumab and control. A numerically higher stroke rate was observed in patients treated with ranibizumab 0.5 mg compared to ranibizumab 0.3 mg or control, however, the differences were not statistically significant. The difference in stroke rates may be greater in patients with known risk factors for stroke, including history of prior stroke or transient ischemic attack. Therefore, these patients should be carefully evaluated by their physicians as to whether ranibizumab treatment is appropriate and whether the benefit outweighs the potential risk.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity with ranibizumab (Lucentis).
Bilateral treatment: Available data do not suggest an increased risk of systemic adverse events with bilateral treatment.
Patient populations with limited data: There are no studies in patients with active systemic infections or in patients with concurrent eye conditions such as retinal detachment or macular hole.
Driving and using machines: The treatment procedure may induce temporary visual disturbances, which may affect the ability to drive or use machines (see Adverse Reactions). Patients who experience these signs must not drive or use machines until these temporary visual disturbances subside.
In adults, transient increases in intraocular pressure (IOP) have been seen within 60 minutes of injection (see Adverse Reactions). Sustained IOP increases have also been reported. Both intraocular pressure and perfusion of the optic nerve head must be monitored and managed appropriately.
Arterial thromboembolic events: There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF (vascular endothelial growth factor) inhibitors. In the wet AMD Phase III studies, the overall frequency of arterial thromboembolic events was similar between ranibizumab and control. A numerically higher stroke rate was observed in patients treated with ranibizumab 0.5 mg compared to ranibizumab 0.3 mg or control, however, the differences were not statistically significant. The difference in stroke rates may be greater in patients with known risk factors for stroke, including history of prior stroke or transient ischemic attack. Therefore, these patients should be carefully evaluated by their physicians as to whether ranibizumab treatment is appropriate and whether the benefit outweighs the potential risk.
Immunogenicity: As with all therapeutic proteins, there is a potential for immunogenicity with ranibizumab (Lucentis).
Bilateral treatment: Available data do not suggest an increased risk of systemic adverse events with bilateral treatment.
Patient populations with limited data: There are no studies in patients with active systemic infections or in patients with concurrent eye conditions such as retinal detachment or macular hole.
Driving and using machines: The treatment procedure may induce temporary visual disturbances, which may affect the ability to drive or use machines (see Adverse Reactions). Patients who experience these signs must not drive or use machines until these temporary visual disturbances subside.
Use In Pregnancy & Lactation
Pregnancy: Risk Summary: For ranibizumab, no clinical data on exposed pregnancies are available.
A study in cynomolgus monkeys does not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/fetal development (see Animal data as follows). 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-/fetotoxic. Therefore, ranibizumab should not be used during pregnancy unless the expected benefit outweighs the potential risk to the fetus. 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.
Animal Data: In pregnant monkeys, IVT administration of ranibizumab did not elicit developmental toxicity or teratogenicity, and had no effect on the weight or structure of the placenta. However due to restrictions dictated by the IVT route of administration, the doses used in the study did not reach maternal toxicity, but achieved a multiple (up to 100-fold) with respect to human systemic exposure.
The absence of ranibizumab-mediated effects on embryo-fetal development is plausibly related to the inability of the antigen-binding fragment (Fab) to cross the placenta due to the absence of an Fc region. Nevertheless, a case was described with high maternal ranibizumab serum levels and presence of ranibizumab in fetal serum, suggesting that the anti-ranibizumab antibody acted as a (Fc region containing) carrier protein for ranibizumab, thereby decreasing its maternal serum clearance and enabling its placental transfer. The embryo-fetal development investigations were performed in healthy pregnant animals and disease (such as diabetes) may modify the permeability of the placenta towards a Fab fragment.
Lactation: There are no data available on the presence of ranibizumab in human milk, the effects of ranibizumab on the breastfed infant or the effects of ranibizumab on milk production/excretion. As a precautionary measure, breast-feeding is not recommended during the use of ranibizumab (Lucentis).
Females and males of reproductive potential Contraception: Females of reproductive potential should use effective contraception during treatment with ranibizumab.
Infertility: There is no fertility data available.
A study in cynomolgus monkeys does not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/fetal development (see Animal data as follows). 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-/fetotoxic. Therefore, ranibizumab should not be used during pregnancy unless the expected benefit outweighs the potential risk to the fetus. 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.
Animal Data: In pregnant monkeys, IVT administration of ranibizumab did not elicit developmental toxicity or teratogenicity, and had no effect on the weight or structure of the placenta. However due to restrictions dictated by the IVT route of administration, the doses used in the study did not reach maternal toxicity, but achieved a multiple (up to 100-fold) with respect to human systemic exposure.
The absence of ranibizumab-mediated effects on embryo-fetal development is plausibly related to the inability of the antigen-binding fragment (Fab) to cross the placenta due to the absence of an Fc region. Nevertheless, a case was described with high maternal ranibizumab serum levels and presence of ranibizumab in fetal serum, suggesting that the anti-ranibizumab antibody acted as a (Fc region containing) carrier protein for ranibizumab, thereby decreasing its maternal serum clearance and enabling its placental transfer. The embryo-fetal development investigations were performed in healthy pregnant animals and disease (such as diabetes) may modify the permeability of the placenta towards a Fab fragment.
Lactation: There are no data available on the presence of ranibizumab in human milk, the effects of ranibizumab on the breastfed infant or the effects of ranibizumab on milk production/excretion. As a precautionary measure, breast-feeding is not recommended during the use of ranibizumab (Lucentis).
Females and males of reproductive potential Contraception: Females of reproductive potential should use effective contraception during treatment with ranibizumab.
Infertility: There is no fertility data available.
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 ranibizumab (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 treated patients included intraocular inflammation and increased intraocular pressure (see Precautions).
The adverse events listed in Table 15 occurred at a higher rate (at least 2 percentage points) in patients receiving treatment with ranibizumab (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 ranibizumab (Lucentis).
DME population: The safety of ranibizumab (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 in Table 15 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 ranibizumab (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 15 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.
RVO population: The safety of ranibizumab (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 ranibizumab (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.
PM population: The safety of ranibizumab (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 15) 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 15.)
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 treated patients included intraocular inflammation and increased intraocular pressure (see Precautions).
The adverse events listed in Table 15 occurred at a higher rate (at least 2 percentage points) in patients receiving treatment with ranibizumab (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 ranibizumab (Lucentis).
DME population: The safety of ranibizumab (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 in Table 15 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 ranibizumab (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 15 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.
RVO population: The safety of ranibizumab (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 ranibizumab (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.
PM population: The safety of ranibizumab (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 15) 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 15.)
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 ranibizumab (Lucentis) 0.2 mg was studied in the6-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.
Retinopathy of Prematurity (ROP) population: The safety of ranibizumab (Lucentis) 0.2 mg was studied in the6-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.
Caution For Usage
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with medicinal products.
Instructions for Use and Handling: Vials (adult and preterm infants): Vials are for single use only (see Dosage & Administration). After injection any unused product must be discarded.
The vial is sterile. Do not use the vial if the packaging is damaged. The sterility of the vial cannot be guaranteed unless the packaging seal remains intact. Do not use the vial if the solution is discolored, cloudy, or contains particulates.
For preparation and intravitreal injection, the following single-use medical devices are needed: a 5 micrometer filter needle (18G), a 1 mL sterile syringe, an injection needle (30G x 1/2 inch).
The 1 mL sterile syringe and the injection needle are not supplied in this pack which only contains the vial and the filter needle.
To prepare ranibizumab (Lucentis) for intravitreal administration, adhere to the following instructions: 1. Before withdrawal, the outer part of the rubber stopper of the vial should be disinfected.
2. Assemble the 5 micrometer filter needle (provided) onto the 1 mL syringe (provided) using aseptic technique. Push the blunt filter needle into the center 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.
6. Aseptically and firmly assemble the injection needle onto the syringe.
7. Carefully remove the cap from the injection needle without disconnecting the injection needle from the syringe.
Note: Grip at the yellow hub of the injection needle while removing the cap.
8. Carefully expel the air from the syringe and adjust the dose to the appropriate mark on the syringe. The dose for adults is 0.05 mL. The dose for preterm infants is 0.02 mL. 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.
Any unused product or waste material should be disposed of in accordance with local requirements.
Instructions for Use and Handling: Vials (adult and preterm infants): Vials are for single use only (see Dosage & Administration). After injection any unused product must be discarded.
The vial is sterile. Do not use the vial if the packaging is damaged. The sterility of the vial cannot be guaranteed unless the packaging seal remains intact. Do not use the vial if the solution is discolored, cloudy, or contains particulates.
For preparation and intravitreal injection, the following single-use medical devices are needed: a 5 micrometer filter needle (18G), a 1 mL sterile syringe, an injection needle (30G x 1/2 inch).
The 1 mL sterile syringe and the injection needle are not supplied in this pack which only contains the vial and the filter needle.
To prepare ranibizumab (Lucentis) for intravitreal administration, adhere to the following instructions: 1. Before withdrawal, the outer part of the rubber stopper of the vial should be disinfected.
2. Assemble the 5 micrometer filter needle (provided) onto the 1 mL syringe (provided) using aseptic technique. Push the blunt filter needle into the center 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.
6. Aseptically and firmly assemble the injection needle onto the syringe.
7. Carefully remove the cap from the injection needle without disconnecting the injection needle from the syringe.
Note: Grip at the yellow hub of the injection needle while removing the cap.
8. Carefully expel the air from the syringe and adjust the dose to the appropriate mark on the syringe. The dose for adults is 0.05 mL. The dose for preterm infants is 0.02 mL. 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.
Any unused product or waste material should be disposed of in accordance with local requirements.
Storage
Store in a refrigerator (2°C to 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.
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.
Action
Pharmacology: Mechanism of action (MOA): Ranibizumab is a humanized 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.
Pharmacodynamics: Binding of VEGF-A to its receptors leads to endothelial cell proliferation and neovascularization, as well as vascular leakage, which are thought to contribute to the progression of the neovascular form of age-related macular degeneration, to the development of CNV secondary to pathologic myopia, or to the macular edema causing visual impairment in diabetes and retinal vein occlusion.
Pharmacodynamics: Binding of VEGF-A to its receptors leads to endothelial cell proliferation and neovascularization, as well as vascular leakage, which are thought to contribute to the progression of the neovascular form of age-related macular degeneration, to the development of CNV secondary to pathologic myopia, or to the macular edema causing visual impairment in diabetes and retinal vein occlusion.
MedsGo Class
Other Eye Preparations
Features
Brand
Lucentis
Full Details
Dosage Strength
10 mg / ml
Drug Ingredients
- Ranibizumab
Drug Packaging
Solution for Injection 2ml x 1's
Generic Name
Ranibizumab
Dosage Form
Solution For Inejction
Registration Number
BR-1072
Drug Classification
Prescription Drug (RX)