Ranibizumab is a medication used in the treatment of various eye conditions, most notably age-related macular degeneration (AMD). It belongs to a class of drugs known as anti-VEGF (vascular endothelial growth factor) agents. AMD is a progressive eye disease that affects the macula, the part of the retina responsible for central vision. Ranibizumab works by inhibiting the activity of VEGF, a protein that promotes the growth of abnormal blood vessels in the eye, which can lead to vision loss in AMD patients. By blocking VEGF, ranibizumab helps to reduce the growth of these abnormal blood vessels and slow the progression of the disease, thereby preserving vision in affected individuals.

Similar to bevacizumab, ranibizumab (Lucentis) is a recombinant humanized IgG1 monoclonal antibody fragment that blocks VEGF-A, or vascular endothelial growth factor.

Ranibizumab (Lucentis) Uses:

• Diabetic retinopathy:
  • Additionally, it is employed in the treatment of diabetic retinopathy.
• Diabetic macular edema:
  • Diabetic macular edema is treated with ranibizumab (DME).
• Macular degeneration:
  • Additionally, it is employed in the treatment of wet neovascular age-related macular degeneration (AMD)
• Myopic choroidal neovascularization:
  • Additionally, it is employed in the management of myopic choroidal neovascularization (mCNV).
• Macular edema:
  • Macular edema treatment after retinal vein blockage (RVO)

Ranibizumab (Lucentis) Dose in Adults

Ranibizumab (Lucentis) Dose in the therapy of Age-related macular degeneration (AMD), neovascular (wet):

• For treating age-related macular degeneration (AMD), specifically the neovascular or "wet" type, the typical dose of ranibizumab is 0.5 milligrams.
• It's given directly into the eye, which is called intravitreal injection.
• Initially, it's usually given once a month, roughly every 28 days.
• After the first three injections, the frequency may decrease.
• For example, it might be reduced to 4 or 5 injections over 9 months.
• Alternatively, after the first 4 injections, it could be given once every 3 months if getting monthly injections is difficult.

Note:

• The goal is to find a balance between maintaining vision and reducing the number of injections.
• A regimen with 4 to 5 doses over 9 months is expected to keep vision stable.
• However, if injections are given every 3 months instead of monthly, there might be a slight loss of vision over 9 months, about 1 line on an eye chart.
• Monthly injections could result in a small gain in vision, about 1 to 2 letters on an eye chart.

Ranibizumab (Lucentis) Dose in the therapy of Diabetic retinopathy (DR):

• In the treatment of diabetic retinopathy (DR), the typical dose of ranibizumab is 0.3 milligrams.
• Similar to its use in AMD, it's administered via intravitreal injection, directly into the eye.
• The usual frequency is once a month, which is approximately every 28 days.
• This consistent monthly dosing helps in managing the progression of diabetic retinopathy by targeting abnormal blood vessel growth in the eye.

Ranibizumab (Lucentis) Dose in the therapy of diabetic macular edema (DME):

• In the treatment of diabetic macular edema (DME), ranibizumab is typically administered via intravitreal injection directly into the eye.
• The standard dose is 0.3 milligrams, given once a month, which translates to approximately every 28 days.
• However, in clinical trials, monthly doses of 0.5 milligrams were also studied as potential treatment options for DME.

Ranibizumab (Lucentis) Dose in the therapy of Myopic choroidal neovascularization (mCNV):

• In the treatment of myopic choroidal neovascularization (mCNV), the standard dose of ranibizumab is 0.5 milligrams.
• It's given via intravitreal injection directly into the eye.
• Typically, it's administered once a month, which is approximately every 28 days.
• This treatment regimen is usually continued for up to 3 months.
• If necessary, further injections may be given after this initial period, depending on the patient's response to treatment and the progression of the condition.

Ranibizumab (Lucentis) Dose in the therapy of Macular edema following retinal vein occlusion (RVO):

• In the treatment of macular edema following retinal vein occlusion (RVO), the standard dose of ranibizumab is 0.5 milligrams.
• As with other conditions, it's administered via intravitreal injection, directly into the eye.
• The typical frequency is once a month, which is approximately every 28 days.
• This consistent monthly dosing helps in managing macular edema by reducing swelling and improving vision in patients with retinal vein occlusion.

Use in Children:

Not indicated.

Ranibizumab Pregnancy Category: B

• Because of how it works, ranibizumab could potentially cause problems during pregnancy, but there's not a lot of information available about using it during pregnancy.
• This means doctors might not know for sure how safe it is for pregnant women.
• A study by Jouve in 2015 mentioned this lack of information about using ranibizumab during pregnancy.

Ranibizumab use during breastfeeding:

• It's uncertain whether ranibizumab can pass into breast milk.
• The manufacturer suggests being careful when giving ranibizumab to women who are breastfeeding.
• This caution is because there isn't enough information available to confirm its safety during breastfeeding.

Dose in Kidney Disease:

• There's no need to change the dosage of ranibizumab for people with kidney problems.

Dose in Liver disease:

• The manufacturer's instructions don't include any adjustments to the dosage of ranibizumab for people with liver problems.

As reported with AMD, RVO, and DME studies:

Common Side Effects of Ranibizumab (Lucentis):

• Cardiovascular:
  • Arterial Thromboembolism
• Hematologic & Oncologic:
  • Anemia
• Central Nervous System:
  • Headache
  • Foreign Body Sensation Of Eye
• Neuromuscular & Skeletal:
  • Arthralgia
• Ophthalmic:
  • Increased Intraocular Pressure
  • Blurred Vision
  • Conjunctival Hemorrhage
  • Eye Pain
  • Vitreous Opacity
  • Intraocular Inflammation
  • Note:
    • Cataracts, blepharitis, dry eye syndrome, eye irritation, increased tearing, maculopathy, ocular hyperemia, eye pruritus, and vitreous detachment occurred in more than 10% of patients, however in some studies these also occurred in similar or higher percentages in control group.
• Respiratory:
  • Nasopharyngitis
  • Bronchitis

Less Common Side Effects of Ranibizumab (Lucentis):

• Cardiovascular:
  • Cerebrovascular Accident
  • Peripheral Edema
  • Atrial Fibrillation
• Endocrine & Metabolic:
  • Hypercholesterolemia
• Central Nervous System:
  • Peripheral Neuropathy
• Gastrointestinal:
  • Gastroesophageal Reflux Disease
  • Nausea
  • Constipation
• Immunologic:
  • Antibody Formation
  • Seasonal Allergy
• Genitourinary:
  • Chronic Renal Failure
• Local:
  • Bleeding At the Injection Site
• Infection:
  • Influenza
• Ophthalmic:
  • Retinal Degeneration
  • Note:
    • In 1% to 10% of patients, conjunctival hyperemia, eye discomfort, posterior capsule opacification, and retinopathy occurred; however, in some studies, these symptoms also occurred at similar or higher rates in the control group.
• Renal:
  • Renal Failure
• Miscellaneous:
  • Wound Healing Impairment
• Respiratory:
  • Sinusitis
  • Upper Respiratory Tract Infection
  • Cough
  • Chronic Obstructive Pulmonary Disease

As Reported with Choroidal Neovascularization Secondary To Pathologic Myopia (Not In US Labeling):

Common Side Effects of Ranibizumab (Lucentis):

• Ophthalmic:
  • Conjunctival Hemorrhage
• Respiratory:
  • Nasopharyngitis

Less Common Side Effects of Ranibizumab (Lucentis):

• Cardiovascular:
  • Hypertension
• Central Nervous System:
  • Headache
  • Migraine
• Endocrine & Metabolic:
  • Diabetes Mellitus
• Gastrointestinal:
  • Abdominal Pain
  • Nausea
  • Toothache
  • Vomiting
• Genitourinary:
  • Urinary Tract Infection
  • Bacteriuria
• Infection:
  • Influenza
• Local:
  • Bleeding At Injection Site
• Neuromuscular & Skeletal:
  • Back Pain
  • Herniated Disk
  • Limb Pain
  • Osteoporosis
• Ophthalmic:
  • Punctate Keratitis
  • Vitreous Opacity
  • Dry Eye Syndrome
  • Eye Pain
  • Increased Intraocular Pressure
  • Blepharitis
  • Conjunctivitis
  • Eyelid Edema
  • Retinal Hole Without Detachment
• Respiratory:
  • Upper Respiratory Tract Infection
  • Pharyngitis

Contraindications to Ranibizumab (Lucentis):

• Ranibizumab shouldn't be used if someone is allergic to it or any part of its formulation, or if they have an ocular (eye) or periocular (around the eye) infection.
• In Canada, there's an additional contraindication not mentioned in the US labeling: it shouldn't be used if there's active inflammation inside the eye.
• This means that if someone has ongoing inflammation within their eye, ranibizumab treatment shouldn't be started until the inflammation is under control.

Cautions and alerts

Endophthalmitis/retinal detachment:

• Intravitreal injections of ranibizumab can sometimes lead to serious complications like endophthalmitis (inflammation within the eye) and retinal detachments.
• It's crucial for healthcare providers to use proper sterile techniques during injections to minimize this risk.
• Patients who receive these injections should be closely monitored for signs of infection, such as eye pain, redness, sensitivity to light, or blurry vision.

Hypersensitivity reactions

• Some individuals may experience hypersensitivity reactions to ranibizumab, which can manifest as severe inflammation within the eye.
• Patients should be instructed to report any intraocular inflammation that worsens in severity.
• Although rare, hypersensitivity reactions such as anaphylaxis have been linked with another VEGF inhibitor called pegaptanib, occurring shortly after its use.
• Therefore, patients receiving ranibizumab injections should be closely monitored for any signs of hypersensitivity.

Increased intraocular pressure

• Before and after receiving an intravitreal injection of ranibizumab, there's a possibility that the pressure inside the eye may rise.
• This increase in intraocular pressure usually happens within 60 minutes after the injection.
• To ensure the patient's safety, it's important to check their intraocular pressure both before and after the injection.
• If the pressure is elevated, appropriate steps should be taken to manage it.
• This monitoring helps in preventing potential complications associated with increased intraocular pressure.

Events that are thromboembolic:

• There's a risk of thromboembolic events, like stroke, being increased after receiving intravitreal injections of VEGF inhibitors such as ranibizumab.
• It's important to be cautious when using these medications in patients with known risk factors for thromboembolic events, such as a history of stroke or transient ischemic attack (TIA).

Diabetic macular edema and diabetic retinopathy are both known as DME.

• In a pooled analysis of trials involving patients with diabetic macular edema (DME) and diabetic retinopathy (DR), there was a higher occurrence of fatal events in those treated with ranibizumab compared to the control group.
• Specifically, about 3% of patients treated with 0.3 mg of ranibizumab experienced fatal events within the first 2 years, whereas only 1% of the control group did.
• While the overall incidence of fatalities was similar to what's typically seen in patients with advanced diabetic complications, it's important to note that a potential link between fatal events and the intravitreal administration of VEGF inhibitors, like ranibizumab, cannot be completely ruled out.

Monitoring parameters:

Monitoring After Ranibizumab Injection

• Intraocular Pressure: Check the pressure inside the eye before and 30 minutes after the injection using tonometry.
• Optic Nerve Head Perfusion: Consider examining the blood flow to the optic nerve head right after the injection.
• Signs of Infection/Inflammation: Keep an eye out for any signs of infection or inflammation during the first week after the injection.
• Retinal Perfusion: Monitor the blood flow in the retina to ensure proper circulation.
• Endophthalmitis: Watch for any signs or symptoms of endophthalmitis, which is inflammation within the eye.
• Visual Acuity: Keep track of changes in visual acuity to gauge the effectiveness of the treatment.

How to administer Ranibizumab (Lucentis)?

For Intravitreal Injection

• Single Eye Treatment: Use each vial or prefilled syringe of ranibizumab for treating only one eye.
• New Equipment for Contralateral Eye: If the other eye also needs treatment, use a new vial or prefilled syringe. Change all sterile equipment including syringe, gloves, drapes, eyelid speculum, filter, and injection needles before administering ranibizumab to the other eye.
• Anesthesia and Antimicrobial Agent: Ensure adequate anesthesia and apply a topical broad-spectrum antimicrobial agent before the procedure.
• Refer to Manufacturer Labeling: For additional detailed instructions and safety information, consult the manufacturer's labeling.

Mechanism of action of Ranibizumab (Lucentis):

• Ranibizumab is a type of medication made from human proteins.
• It's a specialized part of an antibody that's been engineered in the lab.
• This medication works by attaching to and blocking a protein in the body called vascular endothelial growth factor A (VEGF-A).
• By doing this, ranibizumab stops VEGF-A from attaching to its usual targets, slowing down the growth of new blood vessels in the eye.
• This helps to slow down vision loss, particularly in conditions where abnormal blood vessel growth can cause damage to the retina, like age-related macular degeneration.

Absorption:

• After receiving an intravitreal injection, only small amounts of ranibizumab are found in the bloodstream, indicating low absorption into the systemic circulation.
• This means that most of the medication remains localized within the eye, where it's needed.

Half-life elimination:

• In terms of elimination, ranibizumab has a half-life of approximately 9 days in the vitreous humor, the gel-like substance that fills the back portion of the eye.
• This means that it takes about 9 days for half of the medication to be cleared from the vitreous.

International Brand Names of Ranibizumab:

• Lucentis
• Accentrix
• Patizra

Ranibizumab Brand Names in Pakistan: