Ranibizumab (Lucentis) is a recombinant humanized IgG1 monoclonal antibody fragment that inhibits vascular endothelial growth factor A (VEGF-A) similar to bevacizumab.

Ranibizumab (Lucentis) Uses:

• Diabetic macular edema:

  • Ranibizumab is used in the treatment of diabetic macular edema (DME).

• Diabetic retinopathy:

  • It is also used in the management of diabetic retinopathy.

• Macular degeneration:

  • It is also used in the management of neovascular (wet) age-related macular degeneration (AMD)

• Macular edema:

  • Treatment of macular edema following retinal vein occlusion (RVO)

• Myopic choroidal neovascularization:

  • It is also used for the treatment of myopic choroidal neovascularization (mCNV).

Ranibizumab (Lucentis) Dose in Adults

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

• Intravitreal: It is used as 0.5 mg once a month (approximately every 28 days).
• Frequency can be deducted (eg, 4 to 5 injections over 9 months) after the first 3 injections or it can also be reduced after the first 4 injections to once every 3 months if monthly injections are not indicated.

Note:

• A regimen composed of 4 to 5 doses over 9 month period, is expected to maintain visual acuity and an every-3-month dosing regimen has reportedly resulted in approximately 5 letters (1 line) loss of visual acuity over 9 months, as compared to monthly dosing which may result in an additional approximately 1 to 2 letter gain.

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

• Intravitreal: It can be given as 0.3 mg once a month (approximately every 28 days).
• In studies, it can be given as  0.5 mg.

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

• Intravitreal: It is used as 0.3 mg once a month (approximately every 28 days)

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

• Intravitreal: It is used as 0.5 mg once a month approximately every 28 days.

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

• Intravitreal: it is given as 0.5 mg once every 28 days approximately every 28 days for up to 3 months.
• It can be given for retreatment also.

Use in Children:

Not indicated.

Ranibizumab Pregnancy Category: B

• Their mechanism of action can have an impact on the outcome of pregnancy.

Ranibizumab use during breastfeeding:

• It is still not known if breast milk contains it.
• Lactating women should not use Ranibizumab.

Dose in Kidney Disease:

• No renal adjustment is required.

Dose in Liver disease:

• There are no dose adjustment required however, significant exposure is expected in severe renal impairement.

As reported with AMD, RVO, and DME studies:

Common Side Effects of Ranibizumab (Lucentis):

• Cardiovascular:

  • Arterial Thromboembolism

• Central Nervous System:

  • Foreign Body Sensation Of Eye
  • Headache

• Hematologic & Oncologic:

  • Anemia

• Neuromuscular & Skeletal:

  • Arthralgia

• Ophthalmic:

  • Conjunctival Hemorrhage
  • Eye Pain
  • Vitreous Opacity
  • Increased Intraocular Pressure
  • Blurred Vision
  • Intraocular Inflammation
  • Note:
    • Cataract, Blepharitis, Dry Eye Syndrome, Eye Irritation, Increased Lacrimation, Maculopathy, Ocular Hyperemia, Eye Pruritus, And Vitreous Detachment Occurred In >10% Of Patients, But Also Occurred Either In Similar Percentages To The Control Or More Often In The Control In Some Studies.

• Respiratory:

  • Nasopharyngitis
  • Bronchitis

Less Common Side Effects of Ranibizumab (Lucentis):

• Cardiovascular:

  • Peripheral Edema
  • Atrial Fibrillation
  • Cerebrovascular Accident

• Central Nervous System:

  • Peripheral Neuropathy

• Endocrine & Metabolic:

  • Hypercholesterolemia

• Gastrointestinal:

  • Nausea
  • Constipation
  • Gastroesophageal Reflux Disease

• Genitourinary:

  • Chronic Renal Failure

• Immunologic:

  • Antibody Formation
  • Seasonal Allergy

• Infection:

  • Influenza

• Local:

  • Bleeding At Injection Site

• Ophthalmic:

  • Retinal Degeneration
  • Note:
    • Conjunctival Hyperemia, Eye Discomfort, Posterior Capsule Opacification, And Retinopathy Occurred In 1% - 10% Of the patients, But Also Occurred In Similar Percentages To The Control Or More Often In The Control In Some Of The Studies.

• Renal:

  • Renal Failure

• Respiratory:

  • Upper Respiratory Tract Infection
  • Cough
  • Sinusitis
  • Chronic Obstructive Pulmonary Disease

• Miscellaneous:

  • Wound Healing Impairment

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):

• Hypersensitivity is a serious contraindication.

Canadian labeling: Additional contraindications, but not in the US labeling

• It is a serious contraindication to have intraocular inflammation.

Warnings and precautions

• Endophthalmitis/retinal detachment:

  • Intravitreous injections can cause endophthalmitis and retina detachment.
  • When administering an injection, it is important to use aseptic techniques.
  • Acute infections should be checked on patients and reported any symptoms such as blurred vision, eye pain, redness, or photophobia immediately.

• Hypersensitivity reactions

  • Hypersensitivity reactions can occur when there is intraocular inflammation. 
  • Patients should be instructed to report any intraocular inflammation that is increasing in severity.
  • Hypersensitivity reactions are rare and can be associated with pegaptanib (a VEGF inhibitor). It should be closely monitored.
  • Anaphylaxis can be managed with the right equipment.

• Increased intraocular pressure

  • IOP can rise before and after Ranibizumab administration.
  • The usual onset occurs after approximately 60 minutes.
  • After every administration, the IOP should always be measured.

• Events that are thromboembolic:

  • Events such as stroke and VTE are increasing.
  • This medication should not be administered to patients at high risk of venous thromboembolism.

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

  • A pooled analysis of trials involving DME patients and DR patients showed a higher rate of fatalities in patients receiving ranibizumab than in those who received 1% control.
  • The overall incidence of deaths was similar to those seen in patients suffering from advanced diabetes complications.
  • However, it is possible to link fatalities with intravitreal administrations of VEGF inhibitors.

Monitoring parameters:

• Intraocular pressure prior to and 30 minutes following injection via tonometry.
• Consider checking for perfusion of the optic nerve head immediately following injection. signs of infection/inflammation for the first week following injection.
• Retinal perfusion and endophthalmitis.
• Visual acuity.

How to administer Ranibizumab (Lucentis)?

• For ophthalmic intravitreal injection only.
• Each vial or prefilled syringe should only be used for the treatment of a single eye.
• If the contralateral eye requires treatment, a new vial or prefilled syringe should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before ranibizumab is administered to the other eye.
• Adequate anesthesia and a topical broad-spectrum antimicrobial agent should be administered prior to the procedure.
• Refer to manufacturer labeling for additional detailed information.

Mechanism of action of Ranibizumab (Lucentis):

Ranibizumab, a recombinant monoclonal humanized antibody fragment, binds and inhibits human vascular growth factor A (VEGF) Ranibizumab blocks VEGF binding to its receptors, thereby suppressing neovascularization.

Absorption:

• After intravitreal injection, serum levels are low

Half-life elimination:

• Vitreous: ~9 days

International Brand Names of Ranibizumab:

• Lucentis
• Accentrix
• Patizra

Ranibizumab Brand Names in Pakistan: