Vabysmo^® (Solution) Instructions for Use

Marketing Authorization Holder

F. Hoffmann-La Roche, Ltd (Switzerland)

Contact Information

F. Hoffmann-La Roche Ltd. (Switzerland)

ATC Code

S01LA09 (Faricimab)

Active Substance

Faricimab (Rec.INN registered by WHO)

Dosage Form

Vabysmo®

Solution for intraocular administration 120 mg/1 ml: fl. 0.24 ml in a kit with a filter needle

Dosage Form, Packaging, and Composition

Solution for intraocular administration as a clear to opalescent, colorless to brownish-yellow liquid.

* this amount is sufficient to withdraw a single dose of 0.05 ml of solution, which contains 6 mg of faricimab.

Excipients: L-histidine, 30% acetic acid, L-methionine, sodium chloride, D-sucrose, polysorbate 20, water for injections.

0.24 ml – colorless glass vials (1) in a kit with 1 filter needle and an information leaflet – cardboard boxes.

Clinical-Pharmacological Group

Drug used for vascular eye diseases. Anti-neovascularization drug

Pharmacotherapeutic Group

Drugs used in ophthalmology; drugs used for diseases of the uvea; agents preventing neovascularization

Pharmacological Action

Mechanism of action

Faricimab is a humanized bispecific antibody belonging to the immunoglobulin G1 (IgG1) class, which acts by inhibiting two different pathways, neutralizing both Ang-2 and vascular endothelial growth factor A (VEGF-A).

Ang-2 reduces vascular stability, promoting endothelial destabilization, pericyte loss, and pathological angiogenesis, thereby increasing transudation and inflammation. It also increases the sensitivity of blood vessels to VEGF-A activity, leading to their further destabilization. Ang-2 and VEGF-A exhibit synergistic action in increasing vascular permeability and stimulating neovascularization.

Dual inhibition of Ang-2 and VEGF-A by faricimab reduces vascular permeability and inflammation, suppresses pathological angiogenesis, and restores vascular stability.

Pharmacodynamic effects

In 6 phase III clinical studies, a decrease in mean concentrations of free Ang-2 and free VEGF-A in the eye was observed from day 7 of treatment compared to baseline.

nAMD

In phase III studies in patients with nAMD (TENAYA, LUCERNE studies), objective, pre-specified treatment efficacy criteria based on visual function and anatomical parameter assessments, as well as the treating physician’s clinical assessment at disease activity assessment time points (week 20 and week 24), were used for treatment decisions.

When using Vabysmo^® from baseline to week 48, a reduction in mean central subfield thickness (CST) was observed, which was comparable to that with aflibercept. The mean reduction in CST from baseline to the primary endpoint visits (average at week 40-48) was -137 µm and -137 µm for Vabysmo^® administered up to every 16 weeks (up to once/16 weeks), compared to -129 µm and -131 µm for aflibercept in the TENAYA and LUCERNE studies, respectively. The mean reduction in CST was maintained throughout the 2nd year of treatment.

In the TENAYA and LUCERNE studies at week 48, reductions in intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) with Vabysmo^® and aflibercept were comparable and maintained through the 2nd year of treatment (week 104-108).

At week 48, the change in total choroidal neovascularization (CNV) area and the reduction in CNV area from baseline were also comparable between the Vabysmo^® treatment group and the aflibercept group in the TENAYA and LUCERNE studies, respectively.

DME

In phase III studies in patients with DME (YOSEMITE and RHINE), anatomical parameters related to macular edema were part of the disease activity assessment determining treatment decisions.

The mean reduction in CST from baseline at the primary endpoint visits (average at weeks 48-56) was numerically greater in patients treated with Vabysmo^® compared to aflibercept, and was 207 µm and 197 µm in patients receiving Vabysmo^® once/8 weeks and adjustable-dose Vabysmo^® up to once/16 weeks, compared to 170 µm in patients in the aflibercept once/8 weeks group in the YOSEMITE study; in the RHINE study, the results were 196 µm, 188 µm, and 170 µm, respectively. Sequential reductions in CST were observed throughout the treatment. In both studies, absence of IRF and DME (defined as achieving CST less than 325 µm) was achieved in a greater proportion of patients in both Vabysmo^® groups compared to the aflibercept groups.

Macular edema following RVO

In phase III studies in patients with branch retinal vein occlusion (BRVO; BALATON) and central retinal vein occlusion/hemiretinal vein occlusion (CRVO/HRVO; COMINO), a reduction in mean CST from baseline to week 24 was observed with Vabysmo^® administered every 4 weeks (once/4 weeks) and was comparable to that with aflibercept once/4 weeks. In the BALATON and COMINO studies, the reduction in mean CST from baseline to week 24 was 311.4 µm with Vabysmo^® compared to 304.4 µm with aflibercept and 461.6 µm with Vabysmo^® once/4 weeks compared to 448.8 µm with aflibercept once/4 weeks, respectively. The reduction in CST was maintained up to week 72, when patients were switched to treatment with Vabysmo^® in an adjustable dosing regimen up to once/16 weeks.

The proportion of patients in the Vabysmo^® and aflibercept groups who had absence of IRF, absence of SRF, and absence of macular edema (defined as a reduction in CST below 325 µm) over time up to week 24 was comparable in both studies. These results were maintained up to week 72, when patients were switched to treatment with Vabysmo^® in an adjustable dosing regimen up to once/16 weeks.

In the BALATON study at week 24, the proportion of patients without macular edema was 95.3% of patients receiving Vabysmo^® once/4 weeks, compared to 93.9% of patients receiving aflibercept once/4 weeks; the proportion of patients without IRF was 72.5% in the Vabysmo^® once/4 weeks treatment group compared to 66% in the aflibercept once/4 weeks treatment group. The proportion of patients without SRF reached 91.3% in the Vabysmo^® once/4 weeks group and 90.3% in the aflibercept once/4 weeks group.

In the COMINO study, the proportion of patients who did not have macular edema at week 24 was 93.7% in the Vabysmo^® once/4 weeks group and 92% in the aflibercept once/4 weeks group. The proportion of patients without IRF was 76.2% of patients receiving Vabysmo^® once/4 weeks, compared to 70.8% of patients receiving aflibercept once/4 weeks; the proportion of patients without SRF was 96.4% in the Vabysmo^® once/4 weeks treatment group and 93.4% in the aflibercept once/4 weeks treatment group.

Clinical efficacy and safety

Treatment of nAMD

The safety and efficacy of Vabysmo^® in patients with nAMD were evaluated in two randomized, multicenter, 2-year, double-masked, non-inferiority studies with an active comparator – TENAYA and LUCERNE. A total of 1329 patients were enrolled in these studies, of which 1135 (85%) patients completed the studies at week 112. A total of 1326 patients received at least one dose of the drug (664 patients received Vabysmo^®). Patient age ranged from 50 to 99 years, with a mean of 75.9 years.

In both studies, patients were randomized in a 1:1 ratio to one of two treatment groups

• Vabysmo^®, 6 mg, up to once/16 weeks, after the first four monthly doses;
• Aflibercept, 2 mg, once/8 weeks after the first three monthly doses.

After the first four monthly doses (weeks 0, 4, 8, and 12), patients randomized to the Vabysmo^® group received a dose once/16 weeks, every 12 weeks (once/12 weeks) or once/8 weeks based on disease activity assessment at weeks 20 and 24 using objective, pre-specified treatment efficacy criteria based on visual function and anatomical parameter assessments, as well as the treating physician’s clinical assessment. These fixed dosing intervals were maintained in patients until week 60 without additional therapy. From week 60, patients in the Vabysmo^® group switched to an adjustable dose of the drug, where the dosing interval could be increased in 4-week increments (up to once/16 weeks) or decreased in 8-week increments (to once/8 weeks) based on pre-specified treatment efficacy criteria using visual function and anatomical parameter assessments. Patients receiving aflibercept maintained a once/8 week dosing interval throughout the study period. The duration of both studies was 112 weeks.

The primary efficacy endpoint was the change in BCVA from baseline based on the average at weeks 40, 44, and 48, measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In both studies, during the 1st year of treatment, patients receiving Vabysmo^® up to once/16 weeks showed a comparable mean change in BCVA from baseline to patients receiving aflibercept once/8 weeks. Significant visual improvement from baseline was observed at week 112 in both treatment groups. Detailed results of both studies are presented in Table 1, Fig. 1 and Fig. 2 below.

The proportion of patients at each of the different dosing intervals at week 48 in the TENAYA and LUCERNE studies, respectively, was

• Once/16 weeks: 46%, 45%
• Once/12 weeks: 34%, 33%
• Once/8 weeks: 20%, 22%

The proportion of patients at each of the different dosing intervals at week 112 in the TENAYA and LUCERNE studies, respectively, was

• Once/16 weeks: 59%, 67%
• Once/12 weeks: 15%, 14%
• Once/8 weeks: 26%, 19%

Table 1. Efficacy outcomes at the primary endpoint visits of the 1st year^a and 2nd year^b of treatment in the TENAYA and LUCERNE studies

Fig. 5. Mean change in visual acuity from baseline up to week 72 in the BALATON study

Treatment with Vabysmo^® 6 mg in an adjustable regimen up to once/16 weeks was initiated at week 24, although not all patients received Vabysmo^® at week 24.

Fig. 6. Mean change in visual acuity from baseline up to week 72 in the COMINO study

Treatment with Vabysmo^® 6 mg in an adjustable regimen up to once/16 weeks was initiated at week 24, although not all patients received Vabysmo^® at week 24.

Preclinical safety data

Carcinogenicity

Carcinogenicity studies to determine the carcinogenic potential of Vabysmo^® have not been conducted.

Genotoxicity

Studies to determine the mutagenic potential of Vabysmo^® have not been conducted.

Impairment of Fertility

While the antibody components against VEGF and Ang-2 may carry a potential theoretical risk to reproductive function based on the mechanism of action, systemic exposure due to intraocular administration suggests that this risk may be very small. In a 6-month study of Vabysmo^® in cynomolgus monkeys, no effects on fertility were observed.

Reproductive toxicity

Inhibition of VEGF has been demonstrated to cause malformations, embryo-fetal resorption, and reduced fetal weight. Inhibition of VEGF has also been shown to affect follicle development, corpus luteum function, and fertility. Specific studies on the effects of Ang-2 inhibition on pregnancy are lacking. Based on preclinical information, inhibition of Ang-2 may lead to effects comparable to VEGF inhibition. Systemic exposure after intraocular administration of Vabysmo^® is very low.

In a 6-month study of Vabysmo^® in cynomolgus monkeys, no effects on reproductive organs were observed. In an embryo-fetal development study conducted in pregnant female cynomolgus monkeys administered 5 weekly intravenous injections of Vabysmo^®, starting on day 20 of gestation at doses of 1 mg/kg or 3 mg/kg, no effects on pregnancy course or on the fetus were observed. In monkeys at the maximum dose that did not cause observable adverse effects (dose 3 mg/kg), serum exposure (C_max) was more than 500 times higher than in humans at a dose of 6 mg with intraocular administration once every 4 weeks.

Pharmacokinetics

Absorption

Vabysmo^® is administered by intraocular injection to exert a local effect on the eye. Clinical studies of other routes of administration have not been conducted.

Based on population pharmacokinetic analysis (including patients with nAMD and DME, N=2246), the C_max of free (unbound to VEGF-A and Ang-2) faricimab in plasma is estimated to be reached approximately 2 days after administration. In patients with nAMD and DME, the estimated mean (±SD) C_max in plasma is 0.23 (0.07) µg/ml and 0.22 (0.07) µg/ml, respectively.

After repeated administrations, the mean minimum concentrations of free faricimab in plasma are estimated to be 0.002-0.003 µg/ml when administered once/8 weeks.

In the dose range of 0.5-6 mg, faricimab demonstrated dose-proportional pharmacokinetics (based on C_max and area under the concentration-time curve). No accumulation of faricimab in the vitreous humor or plasma was observed after monthly administration.

Pharmacokinetic analysis in patients with nAMD, DME, and macular edema following RVO (N=2977) showed that the pharmacokinetics of faricimab in patients with nAMD, DME, and macular edema following RVO are comparable.

Distribution

The C_max of free faricimab in plasma is predicted to be approximately 600 and 6000 times lower than in the aqueous humor and vitreous humor, respectively, and below the binding affinity for VEGF and Ang-2. Consequently, systemic pharmacodynamic effects are unlikely, which is further supported by the absence of significant changes in free VEGF and Ang-2 plasma concentrations after faricimab treatment in clinical studies.

Population pharmacokinetic analysis demonstrated an effect of age and body weight on the pharmacokinetics of faricimab in the eye or systemic pharmacokinetics, respectively. Both effects were not considered clinically significant; dose adjustment is not required.

No substantial decrease in Ang-2 or VEGF-A plasma concentrations was observed.

Metabolism

The metabolism of faricimab has not been directly studied, as monoclonal antibodies are primarily eliminated by catabolism.

Elimination

The estimated mean apparent systemic T_1/2 of faricimab after intraocular administration is 7.5 days.

Pharmacokinetics in special patient groups

Elderly patients. In six phase III clinical studies, ~58% (1496/2571) of patients randomized to the Vabysmo^® treatment group were aged ≥65 years. Population pharmacokinetic analysis showed an effect of age on the pharmacokinetics of faricimab. This effect is not considered clinically significant.

Renal impairment. A formal pharmacokinetic study in patients with renal impairment has not been conducted.

Hepatic impairment. A formal pharmacokinetic study in patients with hepatic impairment has not been conducted.

Race. The systemic pharmacokinetics of Vabysmo^® are not dependent on race.

Gender. No clinically significant effect of gender on the systemic pharmacokinetics of Vabysmo^® has been shown.

Children. The efficacy and safety of Vabysmo^® in children and adolescents have not been established.

Indications

Adult patients from 18 years of age

• Neovascular (wet) age-related macular degeneration (nAMD);
• Diabetic macular edema (DME);
• Macular edema following retinal vein occlusion (RVO).

ICD codes

Dosage Regimen

Vabysmo^® should be administered by a qualified physician experienced in performing intraocular injections. Each vial should be used for administration into one eye only.

nAMD

The recommended dosing regimen for Vabysmo^® is 6 mg (0.05 ml of solution), administered by intravitreal injection every 4 weeks (loading dose). This treatment regimen is intended for the first 4 doses of the drug.

After the 3-month initial treatment period, the subsequent treatment regimen will be based on anatomical features and visual function characteristics that determine the course of the disease. Assessment of the response to therapy is recommended at week 20 after the first injection (8 weeks after the 4th loading dose) with a possible re-assessment at week 24 after the first injection (12 weeks after the 4th loading dose), allowing for individualization of the treatment regimen depending on the presence or absence of signs of disease activity. In the absence of disease progression, intravitreal injections of Vabysmo^® are recommended every 16 weeks, and if signs of progression appear – every 8 or 12 weeks. Follow-up time points for patient assessment are determined at the physician’s discretion based on the patient’s complaints and general condition; monthly examinations are not provided.

DME

The recommended dosing regimen for Vabysmo^® is 6 mg (0.05 ml of solution), administered by intravitreal injection every 4 weeks. This treatment regimen is intended for the first 4 doses of the drug.

After the initial treatment period, the treatment regimen can be individualized according to the “treat-and-extend” approach based on the assessment of anatomical parameters of the disease course and visual function characteristics. The interval between drug administrations can be changed from 4 to 16 weeks with an interval change step of 4 weeks.

If disease activity changes, a re-evaluation of the drug administration frequency is necessary; reducing the interval by 4 weeks or 8 weeks is possible if needed. Follow-up time points for patient assessment are determined at the physician’s discretion based on the patient’s complaints and general condition; monthly examinations are not provided.

Macular edema following RVO

The recommended dosing regimen for Vabysmo^® is 6 mg (0.05 ml of solution), administered by intravitreal injection every 4 weeks. This treatment regimen is intended for the first 3 or more doses of the drug.

After the initial treatment period, the treatment regimen can be individualized according to the “treat-and-extend” approach based on the assessment of anatomical parameters of the disease course and visual function characteristics. The interval between administrations can be changed from 4 to 16 weeks with an interval change step of 4 weeks. Follow-up time points for patient assessment are determined at the physician’s discretion based on the patient’s complaints and general condition; monthly examinations are not provided.

Duration of treatment

Vabysmo^® is intended for long-term therapy.

Delayed administration or missed dose

If administration is delayed or a dose is missed, the patient should be re-examined at the next possible visit and continue therapy at the physician’s discretion.

If the assessment results of anatomical features and visual function characteristics determining the disease course show that further treatment of the patient is not beneficial, therapy with Vabysmo^® should be discontinued.

Special patient groups

Elderly patients

In six phase III clinical studies, approximately 58% (1496/2571) of patients randomized to the Vabysmo^® treatment group were aged ≥ 65 years. Population pharmacokinetic analysis showed an effect of age on the pharmacokinetics of faricimab. This effect is not considered clinically significant. No dose adjustment is required in patients aged ≥ 65 years (see section “Pharmacokinetics”).

Patients with renal impairment

No specific studies have been conducted on the use of Vabysmo^® in patients with renal impairment. In a pharmacokinetic analysis conducted among patients from four phase III clinical studies, 64% of whom had renal impairment (mild – 38%, moderate – 23%, and severe – 2%), no differences in the systemic pharmacokinetics of faricimab after intravitreal administration of Vabysmo^® were identified.

No dose adjustment is required in patients with renal impairment.

Patients with hepatic impairment

No specific studies have been conducted on the use of Vabysmo^® in patients with hepatic impairment. However, this patient population does not require special attention since the drug is metabolized via proteolysis and is not dependent on liver function.

No dose adjustment is required in patients with hepatic impairment.

Other special patient populations

No specific dose adjustment based on gender or race is required.

Children

The efficacy and safety of Vabysmo^® in children and adolescents under 18 years of age have not been established. No data are available.

Method of administration

For intraocular use only.

Before administration, Vabysmo^® should be inspected visually for particulate matter or discoloration.

Immediately after intraocular injection, patients should be monitored for increased intraocular pressure (IOP). Appropriate monitoring may include checking optic nerve head perfusion or tonometry. If necessary, sterile equipment for paracentesis should be available.

After intraocular injection, patients should be instructed to report any symptoms suggestive of endophthalmitis immediately (e.g., vision loss, eye pain, redness of the eye, photophobia, blurred vision).

Preparation for administration

Vabysmo^® is a sterile, preservative-free, clear to opalescent, colorless to brownish-yellow liquid.

Do not shake.

The vial contains more than the recommended dose of 6 mg. The vial fill volume (0.24 ml) should not be used completely. The excess volume should be discarded before injection. Injection of the entire vial volume leads to overdose. The injection dose should be set at the 0.05 ml mark, which corresponds to 6 mg of faricimab.

After removal from the refrigerator and before administration, the Vabysmo^® vial should be visually inspected. If particles, cloudiness, or discoloration are visible, the vial must not be used.

The contents of the vial are sterile and intended for single use only. Do not use the drug if any component of the packaging, the vial and/or the filter needle is damaged, opened, or if the expiration date has passed.

When preparing Vabysmo^® for administration, proper aseptic technique must always be observed.

It should be ensured that the injection is performed immediately after dose preparation.

Instructions for disposal of unused or expired drug

Environmental release of medicinal products should be minimized. The drug should not be disposed of via wastewater or household waste.

The following recommendations for the use and disposal of syringes and consumables must be strictly adhered to:

• Needles and syringes must never be reused;
• Used needles and syringes should be placed in a puncture-resistant container.

All remaining medicinal product and waste should be disposed of in accordance with established procedures.

Adverse Reactions

In total, the safety population in six phase III clinical studies included 4489 patients (2567 patients received Vabysmo^®: 664 patients with nAMD, 1262 patients with DME, and 641 with macular edema following RVO).

In phase III clinical studies, the most frequently reported reactions were cataract (10%), conjunctival hemorrhage (7%), vitreous detachment (4%), increased IOP (4%), vitreous floaters (4%), eye pain (3%), and retinal pigment epithelium tear (only in nAMD) (3%).

The most serious adverse reactions were cataract (9.7%), uveitis (0.5%), endophthalmitis (0.4%), vitritis (0.4%), retinal tear (0.2%), rhegmatogenous retinal detachment (0.1%), and traumatic cataract (<0.1%).

The safety data presented below include all adverse reactions from the pooled data of six phase III clinical studies in patients with nAMD, DME, and macular edema following RVO, for which there is a reasonable possibility of a causal relationship with the injection procedure or the drug.

Adverse reactions observed during clinical studies are grouped according to the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class. The following categories are used to describe the frequency of adverse reactions: 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).

Table 5. Summary of adverse reactions in patients treated with Vabysmo^® in phase III clinical studies

Description of selected adverse reactions

After intravitreal administration of VEGF inhibitors, there is a theoretical risk of arterial thromboembolic events, including stroke and myocardial infarction. In clinical studies of Vabysmo^® in patients with nAMD, DME, and macular edema following RVO, a low frequency of arterial thromboembolic events was observed. No notable differences were observed between patient groups receiving Vabysmo^® and the comparator drug for all indications.

Immunogenicity

There is a potential for an immune response to the administration of Vabysmo^®. After drug administration up to 112 weeks in nAMD, 100 weeks in DME, and 72 weeks in macular edema following RVO, anti-faricimab antibodies were detected in 13.8% of patients with nAMD, 9.6% of patients with DME, and 14.4% of patients with macular edema following RVO, respectively. The clinical significance of these antibodies and their impact on drug safety are currently unclear. Among patients who tested positive for anti-faricimab antibodies, cases of intraocular inflammation were more frequent, although the overall frequency of a positive test for anti-faricimab antibodies and intraocular inflammation in the entire study population was about 1%. No relationship was found between drug efficacy, its pharmacokinetics, and the presence of anti-faricimab antibodies.

Retinal pigment epithelium tear

Retinal pigment epithelium tear is a complication of retinal pigment epithelium detachment in patients with nAMD and is one of the most common complications of therapy with VEGF inhibitors, including faricimab. This phenomenon occurred more frequently during studies in the initial treatment period in patients receiving Faricimab (2.9%) compared to aflibercept, its severity ranged from mild to moderate, and no effect on visual acuity was noted.

Post-marketing experience

Rare spontaneous cases of retinal vasculitis and/or retinal occlusive vasculitis have been reported, as with other intraocular therapies.

Eye disorders: rare – retinal vasculitis, retinal occlusive vasculitis.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Ocular or periocular infection;
• Active intraocular inflammation;
• Hypersensitivity to faricimab or to any of the excipients.

Use in Pregnancy and Lactation

Women of childbearing potential (contraception in men and women)

Women of childbearing potential should use reliable methods of contraception during treatment with Vabysmo^® and for at least 3 months after the last dose of Vabysmo^®.

Pregnancy

Information on the use of faricimab in pregnant women is limited or absent. Systemic exposure to Vabysmo^® after intravitreal administration is extremely low.

In a study of the drug’s effect on pregnancy conducted in pregnant cynomolgus monkeys, no data were obtained on direct or indirect effects of the drug on embryofetal development, or on the reproductive system as a whole. As a precaution, the use of Vabysmo^® in pregnant women is not recommended, except in cases where the benefit of the drug to the mother outweighs the risk to the fetus and child.

Breastfeeding period

It is unknown whether Vabysmo^® or its metabolites are excreted in human breast milk. No studies have been conducted to assess the effect of Vabysmo^® on breast milk production or to determine its presence in breast milk. Since many drugs are excreted in breast milk, caution should be exercised when prescribing Vabysmo^® to a nursing woman. A decision should be made either to discontinue breastfeeding or to discontinue Vabysmo^® therapy, taking into account the benefit of breastfeeding for the child’s development and growth and the benefit of therapy for the woman, as well as the potential adverse effects of Vabysmo^® on the child.

Fertility

Studies of reproductive function or fertility have not been conducted. In a 6-month study of Vabysmo^® in cynomolgus monkeys, no effects on reproductive organs or fertility were observed.

Use in Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment.

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment.

Pediatric Use

The use of the drug in children and adolescents under 18 years of age is contraindicated (the efficacy and safety of the drug in this category of patients have not been studied).

Geriatric Use

No dose adjustment is required in patients aged ≥65 years (see section “Pharmacokinetics”).

Special Precautions

To improve the traceability of biological medicinal products, the trade name and batch number of the administered drug should be clearly recorded.

Reactions associated with intraocular injection

Intraocular injection, including of Vabysmo^®, has been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear, and iatrogenic traumatic cataract.

Proper aseptic technique must always be observed when administering Vabysmo^®. Patients should be instructed to report any symptoms, such as pain, vision loss, photophobia, blurred vision, floaters, or redness, suggestive of endophthalmitis or any of the aforementioned events immediately to ensure prompt and appropriate treatment.

Within 60 minutes after intraocular injection, including of Vabysmo^®, a temporary increase in IOP has been observed. Transient IOP elevation above 21 mmHg in some cases persisted for 2 or more consecutive visits. Special precautions should be taken in patients with poorly controlled glaucoma (Vabysmo^® should not be administered if IOP ≥30 mmHg). In all cases, IOP and optic nerve head perfusion should be monitored and treatment administered if necessary.

Systemic Effects

Following intravitreal administration, systemic adverse events, including arterial thromboses, have been reported. There is a theoretical risk that these may be associated with VEGF inhibition. In clinical studies of faricimab in patients with nAMD, DME, and macular edema due to RVO, a low frequency of new arterial thromboembolic events was observed.

Immunogenicity

Development of an immune reaction to Vabysmo^® is possible due to its nature as a protein-based medicinal product. Patients should be instructed to report any signs or symptoms of intraocular inflammation, such as vision loss, eye pain, increased sensitivity to light, floaters, or increased eye redness, as these may be clinical signs of hypersensitivity.

Bilateral Therapy

The safety and efficacy of Vabysmo^® when administered simultaneously in both eyes have not been studied.

Concomitant Use with Other Anti-VEGF Antibodies

Data on the concomitant use of Vabysmo^® with other anti-VEGF medicinal products in the same eye are not available.

Treatment Interruption

Treatment should be interrupted in patients:

• With rhegmatogenous retinal detachment, stage 3 or 4 macular hole, or retinal tear; treatment should not be resumed until full recovery;
• With a treatment-related decrease in best-corrected visual acuity (BCVA) of ≥30 letters compared to the last visual acuity assessment; therapy should not be resumed before the next scheduled administration;
• Who have undergone or are scheduled for intraocular surgery within the previous or subsequent 28 days; treatment should not be resumed before the next scheduled administration.

Retinal Pigment Epithelium Tear

Risk factors associated with the development of a retinal pigment epithelium tear following anti-VEGF therapy for nAMD include large and/or superiorly located pigment epithelial detachment. Caution should be exercised when initiating therapy with Vabysmo^® in patients with risk factors for retinal pigment epithelium tear.

Patient Populations with Limited Data

Experience in treating patients with DME with a glycated hemoglobin (HbA1c) level >10%, patients at high risk of proliferative diabetic retinopathy (DR), or patients with nAMD, DME, and macular edema due to RVO with active systemic infections is limited. There is no experience with Vabysmo^® in patients with diabetes mellitus or macular edema due to RVO and uncontrolled arterial hypertension. When treating such patients, the physician should take into account the lack of relevant information.

Effect on Ability to Drive and Use Machines

Vabysmo^® may have a minor influence on the ability to drive and use machines due to possible temporary visual disturbances after the intraocular injection and the accompanying ocular examinations. Patients should not drive or use machines until visual function has sufficiently recovered.

Overdose

Doses exceeding the recommended ones have not been studied. Overdose with a volume greater than recommended may increase IOP.

In case of overdose, IOP should be monitored and, if deemed necessary by the physician, appropriate treatment should be initiated.

Drug Interactions

Interaction studies have not been performed.

Due to the lack of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Storage Conditions

The medicinal product should be stored in the original package (carton to protect from light), in a place out of the reach of children, at a temperature between 2°C (35.6°F) and 8°C (46.4°F). Do not freeze. Do not shake.

Shelf Life

The shelf life is 2 years 6 months. The medicinal product should not be used after the expiry date.

Before use, the unopened vial may be kept at room temperature from 20°C (68°F) to 25°C (77°F) for up to 24 hours.

It should be ensured that the injection is administered immediately after dose preparation.

Dispensing Status

The medicinal product is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.