Epruvy: Uses, Dosage & Side Effects

What Is Epruvy and What Is It Used For?

Epruvy contains the active substance ranibizumab, a humanised monoclonal antibody fragment produced using recombinant DNA technology in Escherichia coli. It is classified as an anti-VEGF (vascular endothelial growth factor) agent and belongs to the broader class of antineovascularisation medicines used in ophthalmology. Ranibizumab selectively binds to and neutralises VEGF-A, a signalling protein that plays a central role in the pathological processes underlying several sight-threatening retinal conditions.

VEGF-A promotes the growth of new, fragile blood vessels (a process called neovascularisation) and increases vascular permeability, leading to fluid leakage and swelling within the retina. These processes are the driving force behind progressive vision loss in conditions such as wet age-related macular degeneration (AMD), diabetic macular oedema (DME), and macular oedema secondary to retinal vein occlusion (RVO). By blocking VEGF-A, ranibizumab reduces neovascularisation, decreases vascular leakage, and helps restore or stabilise visual function.

Epruvy is authorised by the European Medicines Agency (EMA) as a biosimilar of the reference medicine Lucentis, which was first approved in the EU in 2007. As a biosimilar, Epruvy has undergone rigorous comparability studies demonstrating that it is highly similar to Lucentis in terms of quality, safety, and efficacy, with no clinically meaningful differences. The biosimilar was authorised in the EU in September 2024, manufactured by Midas Pharma GmbH.

Approved Indications

Epruvy is approved for the treatment of the following conditions in adults:

• Neovascular (wet) age-related macular degeneration (AMD) – the leading cause of severe vision loss in people over 50, characterised by the growth of abnormal blood vessels under the macula that leak fluid and blood.
• Visual impairment due to diabetic macular oedema (DME) – swelling of the central retina caused by fluid leakage from damaged blood vessels in patients with diabetes mellitus, a major cause of blindness in working-age adults.
• Proliferative diabetic retinopathy (PDR) – an advanced stage of diabetic eye disease characterised by the growth of new, fragile blood vessels on the retinal surface that can bleed and cause retinal detachment.
• Visual impairment due to macular oedema secondary to retinal vein occlusion (RVO) – including both branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), where blockage of retinal veins leads to fluid accumulation and swelling in the macula.
• Visual impairment due to choroidal neovascularisation (CNV) – abnormal blood vessel growth originating from the choroid layer beneath the retina, which may occur secondary to pathologic myopia or other causes.

Mechanism of Action

Ranibizumab is a 48-kDa humanised monoclonal antibody fragment (Fab) that was specifically engineered for ocular use. Unlike full-length antibodies, the smaller Fab fragment is designed to penetrate the retinal layers more effectively after intravitreal injection. It binds with high affinity to all biologically active isoforms of VEGF-A (including VEGF110, VEGF121 and VEGF165), preventing VEGF-A from interacting with its receptors (VEGFR-1 and VEGFR-2) on the surface of endothelial cells.

By blocking VEGF-A signalling, ranibizumab produces several therapeutic effects: it inhibits the proliferation and migration of vascular endothelial cells, reduces pathological neovascularisation, decreases vascular permeability, and suppresses the inflammatory cascade associated with retinal vascular diseases. In clinical practice, these effects translate to reduced retinal oedema, regression of abnormal blood vessels, decreased retinal haemorrhage, and ultimately improved or stabilised visual acuity.

What Should You Know Before Taking Epruvy?

Contraindications

Epruvy is contraindicated (must not be used) in the following situations:

• Hypersensitivity – Known allergy to ranibizumab or any of the excipients (trehalose dihydrate, histidine hydrochloride monohydrate, histidine, polysorbate 20, or water for injections).
• Active or suspected ocular or periocular infections – Any active infection in or around the eye, as intravitreal injection could worsen the infection or introduce pathogens.
• Active severe intraocular inflammation – Active inflammation inside the eye (uveitis or endophthalmitis) that could be exacerbated by the injection procedure.

Warnings and Precautions

Intravitreal injections, including those with Epruvy, carry inherent risks related to the procedure itself. The most serious potential complication is endophthalmitis (severe infection inside the eye), which can lead to permanent vision loss if not promptly treated. To minimise this risk, each injection must be performed under strict aseptic conditions by a qualified ophthalmologist experienced in intravitreal injections. Patients are typically monitored for the first week after each injection for signs of infection.

Temporary increases in intraocular pressure (IOP) have been observed within 60 minutes following intravitreal injection of ranibizumab. Sustained IOP elevations have also been reported with repeated injections. Intraocular pressure and optic nerve head perfusion should be monitored and managed appropriately, particularly in patients with pre-existing glaucoma. The injection should not be administered if the IOP is 30 mmHg or higher.

There is a theoretical risk of arterial thromboembolic events (ATEs), including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. Although the systemic exposure after intravitreal injection is minimal, patients with known risk factors for stroke or cardiovascular disease should be counselled about this potential risk. Clinical trial data have shown a low overall incidence of ATEs, but caution is warranted in high-risk populations.

Retinal detachment and retinal tears are uncommon but serious complications associated with intravitreal injections. Patients should be instructed to report any sudden onset of floaters, flashes of light, or visual field defects immediately, as these may indicate a retinal tear or detachment requiring urgent surgical intervention.

Pregnancy and Breastfeeding

Epruvy should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the foetus. There are no adequate and well-controlled studies of ranibizumab in pregnant women. As a VEGF inhibitor, ranibizumab has the theoretical potential to affect embryo-foetal development, since VEGF signalling plays important roles in angiogenesis during development. Animal reproductive toxicity studies with ranibizumab have been limited, and the systemic exposure following intravitreal injection is expected to be very low.

Women of childbearing potential should use effective contraception during treatment with Epruvy and for at least three months after the last intravitreal injection. If pregnancy occurs during treatment, the potential risks should be discussed with the treating ophthalmologist and obstetrician.

It is not known whether ranibizumab is excreted in human breast milk. Because many drugs are excreted in human milk and due to the potential for adverse effects in the nursing infant, a decision must be made whether to discontinue breastfeeding or to discontinue treatment, taking into account the benefit of therapy for the mother. As a precaution, breastfeeding is not recommended during treatment with Epruvy.

How Does Epruvy Interact with Other Drugs?

Because ranibizumab is administered locally by intravitreal injection, systemic drug-drug interactions are not expected to be clinically relevant. The systemic exposure following intravitreal injection of 0.5 mg ranibizumab is very low, with peak serum concentrations approximately 90,000-fold lower than those in the vitreous humour. Ranibizumab is a protein (antibody fragment) that is degraded by normal cellular catabolic pathways rather than hepatic cytochrome P450 enzymes, which further reduces the likelihood of pharmacokinetic interactions.

No formal drug-drug interaction studies have been conducted with ranibizumab. However, clinical experience and post-marketing surveillance have identified one notable interaction of clinical importance.

Major Interactions

Minor Interactions

No clinically significant minor drug interactions have been identified with ranibizumab. Due to its local administration and minimal systemic absorption, Epruvy is not expected to interact with commonly used systemic medications including antihypertensives, anticoagulants, antiplatelet agents, diabetes medications, or other ophthalmic drops used concomitantly for conditions such as glaucoma or dry eye syndrome.

Patients receiving anticoagulant therapy (such as warfarin or direct oral anticoagulants) may have a higher risk of subconjunctival or vitreous haemorrhage following the injection procedure. This is related to the bleeding risk from anticoagulation rather than a pharmacological interaction with ranibizumab itself. Ophthalmologists should assess bleeding risk before each injection and apply appropriate haemostatic measures.

What Is the Correct Dosage of Epruvy?

Epruvy is supplied as a 10 mg/mL solution for injection, with each single-use vial containing 2.3 mg of ranibizumab in 0.23 mL of solution. From each vial, the ophthalmologist draws up the required injection volume of 0.05 mL, corresponding to a dose of 0.5 mg ranibizumab. The injection is administered directly into the vitreous cavity (intravitreal injection) using a 30-gauge needle under aseptic conditions.

Adults

Dosing regimens vary depending on the indication being treated, but the fundamental principle across all indications is the same: treatment is initiated with a loading phase of regular monthly injections, followed by a maintenance phase where the interval between injections is adjusted according to individual disease activity and treatment response.

Children

The safety and efficacy of Epruvy in children and adolescents below 18 years of age have not been established. There are limited data on the use of ranibizumab in the paediatric population. In some cases, ranibizumab has been used off-label in paediatric patients with conditions such as retinopathy of prematurity (ROP), but Epruvy is not indicated for this use and dosing in children has not been defined in the product labelling.

Elderly

No dose adjustment is required for elderly patients. Ranibizumab has been extensively studied in populations where the majority of participants were over 65 years of age, particularly in the wet AMD trials. The pharmacokinetics, safety, and efficacy of ranibizumab are not significantly affected by age. However, elderly patients may have a higher baseline risk of cardiovascular events, and this should be considered when assessing the benefit-risk profile of treatment.

Missed Dose

If a scheduled injection appointment is missed, the patient should contact their ophthalmologist as soon as possible to reschedule. Delaying treatment may allow disease activity to resume, potentially leading to worsening vision. The ophthalmologist will assess the current disease status at the next visit and determine whether to resume the previous injection schedule or reinitiate a loading phase, depending on how much time has elapsed and the degree of any disease reactivation.

Overdose

Cases of accidental overdose have been reported in clinical trials and post-marketing experience, primarily involving injection of volumes greater than the recommended 0.05 mL. Overdose may result in increased intraocular pressure due to the larger volume within the vitreous cavity. In the event of overdose, intraocular pressure should be monitored and treated as clinically indicated. The ophthalmologist may perform anterior chamber paracentesis (removal of a small amount of aqueous humour) to reduce the pressure if necessary. No specific antidote for ranibizumab overdose exists, and management is supportive.

What Are the Side Effects of Epruvy?

The safety profile of Epruvy is expected to be equivalent to that of the reference medicine Lucentis, based on comprehensive biosimilarity studies. The most frequently reported adverse reactions in clinical trials of ranibizumab are ocular events associated with the intravitreal injection procedure or the pharmacological activity of the drug. The following side effects have been documented in controlled clinical trials and post-marketing surveillance.

Most side effects are mild to moderate in severity and resolve without specific treatment within a few days after the injection. However, some adverse events can be sight-threatening and require immediate medical attention. Patients should be informed about the signs and symptoms of serious complications before starting treatment.

The risk of endophthalmitis is estimated at approximately 0.02–0.05% per injection when proper aseptic technique is used. Symptoms typically develop within the first few days after injection and include severe eye pain, worsening redness, sensitivity to light, and rapidly declining vision. Endophthalmitis is a medical emergency requiring immediate treatment with intravitreal antibiotics.

Arterial thromboembolic events have been observed at a low incidence in clinical trials of anti-VEGF agents. In the pivotal ranibizumab trials (MARINA and ANCHOR), the overall stroke rate was approximately 0.7–1.2% per year, compared with 0.5–0.7% in the control groups. While the absolute risk increase is small, patients with pre-existing cardiovascular risk factors should be informed.

How Should You Store Epruvy?

Epruvy is a biological medicine that requires specific storage conditions to maintain its potency, sterility and stability. Proper storage is essential to ensure the medicine remains effective and safe for use.

The recommended storage conditions for Epruvy are as follows:

• Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Freezing: Do not freeze. If the solution has been frozen, it must be discarded and not used.
• Light protection: Store the vial in the original outer carton to protect from light.
• Shelf life: Refer to the expiry date printed on the carton and vial label. Do not use after the expiry date.
• After opening: Epruvy is supplied in single-use vials. Any unused solution must be discarded after the injection. The vial is not designed for multiple uses.

In practice, Epruvy is stored and handled by the ophthalmology clinic or hospital pharmacy. The medicine is typically brought to room temperature prior to injection but should not be left out of the refrigerator for extended periods. If the medicine is removed from the refrigerator, it may be stored at room temperature (up to 25°C / 77°F) for up to 24 hours before use, provided the vial has not been opened.

As with all injectable medicines, the solution should be visually inspected before administration. It should appear clear to slightly opalescent, colourless to pale yellow. If particles, cloudiness, or discolouration are observed, the vial must not be used.

What Does Epruvy Contain?

Epruvy is formulated as a sterile, preservative-free solution for intravitreal injection. The formulation is designed to maintain the stability and biological activity of the ranibizumab antibody fragment during storage and administration.

Active Substance

Ranibizumab is the active substance in Epruvy. It is a humanised monoclonal antibody fragment (Fab) with a molecular weight of approximately 48 kilodaltons. Ranibizumab is produced by recombinant DNA technology using an Escherichia coli expression system. Each vial contains 2.3 mg of ranibizumab in 0.23 mL of solution, providing a concentration of 10 mg/mL. The recommended injection dose of 0.5 mg is delivered in 0.05 mL of this solution.

Excipients (Inactive Ingredients)

• Trehalose dihydrate – A stabiliser that protects the protein from denaturation during storage.
• Histidine hydrochloride monohydrate – A buffering agent that helps maintain the pH of the solution at approximately 5.5.
• Histidine – Works in conjunction with histidine hydrochloride as part of the buffer system.
• Polysorbate 20 – A surfactant that prevents aggregation and adsorption of the protein to the vial surface.
• Water for injections – The solvent used to prepare the sterile solution.

The solution does not contain any preservatives, antimicrobial agents, or latex. Each vial is designed for single use only. Patients with known allergies to any of the above excipients should inform their ophthalmologist before treatment. Polysorbate 20 is a non-ionic surfactant commonly used in biological formulations and is generally well tolerated, though rare hypersensitivity reactions have been reported.