Ranibizumab

Usage

Ranibizumab is prescribed for the treatment of neovascular (wet) age-related macular degeneration (NVAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy (DR), and myopic choroidal neovascularization (mCNV). It is a vascular endothelial growth factor (VEGF) inhibitor, specifically classified as an anti-angiogenic agent. Ranibizumab works by binding to and inhibiting vascular endothelial growth factor A (VEGF-A), a protein that promotes the growth of new blood vessels. By inhibiting VEGF-A, ranibizumab reduces the formation of abnormal blood vessels in the eye, which are responsible for the vision loss associated with these conditions.

Alternate Names

Ranibizumab is also known internationally by the same name. Popular brand names include Lucentis, Byooviz, and Susvimo (the latter being an intravitreal implant).

How It Works

Pharmacodynamics: Ranibizumab exerts its therapeutic effect by binding with high affinity to all isoforms of human VEGF-A, thereby preventing VEGF-A from binding to its receptors (VEGFR-1 and VEGFR-2) on the surface of endothelial cells. This inhibition of VEGF-A signaling suppresses neovascularization and vascular leakage, leading to a reduction in macular edema and stabilization or improvement of vision.

Pharmacokinetics: Following intravitreal injection, ranibizumab reaches peak serum concentrations within 1 to 3 days. Its systemic half-life is approximately 9 days. Due to its large molecular weight, systemic exposure is minimal after intravitreal administration. Ranibizumab is primarily eliminated through target-mediated drug disposition, involving binding to VEGF-A and subsequent degradation within the eye. Some systemic elimination also occurs via proteolytic degradation. Ranibizumab is not extensively metabolized by CYP enzymes. The elimination pathways are largely ocular, not renal or hepatic.

Mode of Action: Ranibizumab acts by binding directly to VEGF-A, preventing the interaction of VEGF-A with its receptors. This receptor blockade inhibits downstream signaling pathways that promote angiogenesis, vascular permeability, and inflammation.

Dosage

Standard Dosage

Adults:

The standard dosage for most indications is 0.5 mg (0.05 mL of a 10 mg/mL solution) administered as an intravitreal injection. For diabetic macular edema and diabetic retinopathy, the recommended dose is 0.3 mg. Injections are typically given once a month. The Susvimo implant delivers a consistent dose and is typically refilled every six months.

Children:

For retinopathy of prematurity (ROP) in preterm infants, the recommended dose is 0.2 mg (0.02 mL of a 10 mg/mL solution) administered as a single intravitreal injection. Up to three injections per eye may be given within six months if disease activity persists. For other indications, the safety and efficacy of ranibizumab in children and adolescents have not been established.

Special Cases:

• Elderly Patients: No dose adjustment is required in elderly patients.

• Patients with Renal Impairment: No dose adjustment is required.

• Patients with Hepatic Dysfunction: No dose adjustment is required.

• Patients with Comorbid Conditions: Close monitoring is recommended for patients with comorbid conditions, particularly those with diabetes, cardiovascular disease, or a history of thromboembolic events.

Clinical Use Cases

Ranibizumab is not indicated for systemic use. Its administration is restricted to intravitreal injection by qualified ophthalmologists. Therefore, it is not applicable for clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose adjustments are not typically needed for renal or hepatic impairment or in the elderly. For patients with suboptimal response after initial monthly injections, the physician may consider more frequent dosing or switching to monthly dosing for an enhanced treatment effect.

Side Effects

Common Side Effects:

Conjunctival hemorrhage, eye pain, blurred vision, floaters, increased intraocular pressure, eye irritation (itching, tearing, redness).

Rare but Serious Side Effects:

Endophthalmitis, retinal detachment, retinal tear, iatrogenic traumatic cataract, serious intraocular inflammation.

Long-Term Effects:

The long-term effects of ranibizumab are still being studied, but potential complications from chronic use may include geographic atrophy, cataracts, and glaucoma.

Adverse Drug Reactions (ADR):

Any severe allergic reaction (anaphylaxis), severe intraocular inflammation, sudden vision loss.

Contraindications

• Ocular or periocular infections.
• Active intraocular inflammation.
• Hypersensitivity to ranibizumab or any of its excipients.

Drug Interactions

No formal drug interaction studies have been performed. Concomitant use with verteporfin photodynamic therapy (PDT) should be approached cautiously due to the risk of intraocular inflammation.

Pregnancy and Breastfeeding

• Pregnancy: Ranibizumab is potentially teratogenic. Women of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose. If pregnancy occurs during treatment, discuss the potential risks with a physician.

• Breastfeeding: Ranibizumab may be present in human milk at low levels. Due to the potential for absorption and effects on the infant, breastfeeding is not recommended during treatment and for a period after the last dose as determined by a physician in consultation with the mother.

Drug Profile Summary

• Mechanism of Action: Inhibits VEGF-A, suppressing neovascularization and vascular leakage.

• Side Effects: Conjunctival hemorrhage, eye pain, blurred vision, serious intraocular inflammation (rare).

• Contraindications: Ocular/periocular infections, active intraocular inflammation, hypersensitivity.

• Drug Interactions: Limited data, caution with verteporfin.

• Pregnancy & Breastfeeding: Avoid use during pregnancy and breastfeeding.

• Dosage: 0.5 mg monthly intravitreal injection (0.3 mg for DME and DR; 0.2 mg for ROP).

• Monitoring Parameters: Visual acuity, intraocular pressure, signs of infection or inflammation.

Popular Combinations

Ranibizumab is typically used as monotherapy. In some cases, it may be used in combination with laser photocoagulation, although this approach is less common now with the availability of effective anti-VEGF agents.

Precautions

Pre-screening for ocular infections and inflammation is essential. Monitor for signs of endophthalmitis or retinal detachment. Ensure the injection procedure follows strict aseptic technique. Patients should be educated about potential side effects and instructed to report any changes in vision immediately.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ranibizumab?

A: The standard dosage for adults is 0.5 mg via intravitreal injection once a month. The dose for DME and DR is 0.3 mg, and for ROP in infants, it’s 0.2 mg as a single injection.

Q2: How is Ranibizumab administered?

A: Ranibizumab is administered via intravitreal injection by a qualified ophthalmologist. The Susvimo implant is surgically inserted and requires refills approximately every six months.

Q3: What are the common side effects of Ranibizumab?

A: Common side effects include conjunctival hemorrhage, eye pain, blurred vision, floaters, and increased intraocular pressure.

Q4: What are the serious side effects of Ranibizumab?

A: Rare but serious side effects include endophthalmitis, retinal detachment, and retinal tears. Patients should be monitored closely for these complications.

Q5: Can Ranibizumab be used during pregnancy or breastfeeding?

A: Ranibizumab is contraindicated during pregnancy due to its potential teratogenic effects. Breastfeeding is also not recommended while on Ranibizumab treatment.

Q6: How often should patients be monitored during treatment?

A: Patients should be monitored regularly, especially during the initial phase of treatment, with assessments of visual acuity, intraocular pressure, and for any signs of infection or inflammation. The frequency of monitoring depends on the patient’s specific condition and response to treatment.

Q7: What is the difference between Lucentis and Susvimo?

A: Lucentis is administered as monthly intravitreal injections, while Susvimo is an intravitreal implant that delivers a consistent dose of ranibizumab and is refilled every six months.

Q8: Is there a risk of developing resistance to Ranibizumab?

A: While uncommon, some patients may experience a decreased response to Ranibizumab over time. The physician may consider adjusting the dosing frequency or exploring alternative treatment options in such cases.

Q9: Are there any contraindications for using Ranibizumab?

A: Ranibizumab is contraindicated in patients with active or suspected ocular/periocular infections, active intraocular inflammation, or hypersensitivity to the drug.

This information is current as of February 17, 2025, and is intended for qualified Indian doctors. Medical practices and guidelines are subject to change, and it’s always crucial to consult with the latest research and updated recommendations.