Ranibizumab (Monograph)

Brand name: Lucentis
Drug class: EENT Drugs, Miscellaneous
VA class: OP900
Chemical name: Disulfide with human-mouse monoclonal rhuFAB V2 light chain anti-(human vascular endothelial growth factor) Fab fragment (human-mouse monoclonal rhuFAB V2 γ1-chain) immunoglobulin G1
Molecular formula: C₂₁₅₈H₃₂₈₂N₅₆₂O₆₈₁ S₁₂
CAS number: 347396-82-1

Medically reviewed by Drugs.com on Jan 22, 2024. Written by ASHP.

Introduction

Recombinant humanized immunoglobulin G₁ kappa (IgG₁ kappa) monoclonal antibody fragment; a vascular endothelial growth factor A (VEGF-A) antagonist.

Uses for Ranibizumab

Neovascular Age-related Macular Degeneration

Treatment of neovascular (wet) age-related macular degeneration.

Macular Edema Following Retinal Vein Occlusion

Treatment of macular edema following retinal vein occlusion.

Diabetic Macular Edema

Treatment of diabetic macular edema.

Diabetic Retinopathy in Patients with Diabetic Macular Edema

Treatment of diabetic retinopathy (proliferative or nonproliferative) in patients with diabetic macular edema.

Ranibizumab Dosage and Administration

Administration

Ophthalmic Administration

Administer by intravitreal injection only into the affected eye(s).

Commercially available as single-use vials containing 0.3 or 0.5 mg of the drug for intravitreal injection. Prior to intravitreal administration, withdraw entire contents of the appropriate strength ranibizumab vial a sterile 5-µm, 19-gauge filter needle (provided by manufacturer) into a 1-mL tuberculin syringe using aseptic technique. Next, replace filter needle with a sterile 30-gauge, ½-inch needle (provided by manufacturer) for intravitreal injection. To obtain appropriate dose (0.3 or 0.5 mg), expel contents in tuberculin syringe until plunger tip is aligned with the line that marks 0.05 mL on the syringe.

Inject under controlled aseptic conditions (including use of sterile gloves, sterile drape, a sterile eyelid speculum [or equivalent]) following adequate anesthesia and administration of a broad-spectrum anti-infective agent.

Monitor patients for elevation of IOP prior to and 30 minutes following intravitreal injection using tonometry. Monitoring may include evaluation of optic nerve head perfusion immediately after injection. Monitor patients for any manifestations of endophthalmitis. (See Advice to Patients.)

Each vial should be used only for treatment of a single eye. If contralateral eye requires treatment, use a new vial; change sterile field, syringe, gloves, drape, eyelid speculum, and filter and injection needles before administering to the other eye.

Dosage

Adults

Neovascular Age-related Macular Degeneration

Ophthalmic

Intravitreal injection: 0.5 mg (0.05 mL of a solution containing 10 mg/mL) into the affected eye(s) once every month (approximately every 28 days).

After the first several months of therapy, may reduce dosing frequency to decrease treatment burden; however, less frequent dosing regimens are not as effective as continuous monthly dosing and patients should be evaluated regularly.

After the first 3 monthly injections, may reduce to as-needed dosing with regular clinical assessment; while a regimen averaging 4–5 injections over the following 9 months is expected to maintain visual acuity, continuous monthly dosing can result in additional gains (by 1–2 letters).

After the first 4 monthly injections, may reduce dosing frequency to one injection every 3 months; compared with continuous monthly dosing, such a regimen has been shown to result in an approximate 5-letter (1-line) loss of visual acuity over 9 months.

Macular Edema Following Retinal Vein Occlusion

Ophthalmic

Intravitreal injection: 0.5 mg (0.05 mL of a solution containing 10 mg/mL) into the affected eye(s) once every month (approximately every 28 days).

Diabetic Macular Edema

Ophthalmic

Intravitreal injection: 0.3 mg (0.05 mL of a solution containing 6 mg/mL) into the affected eye(s) once every month (approximately every 28 days).

Diabetic Retinopathy in Patients with Diabetic Macular Edema

Ophthalmic

Intravitreal injection: 0.3 mg (0.05 mL of a solution containing 6 mg/mL) into the affected eye(s) once every month (approximately every 28 days).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No dosage adjustment required. (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Ranibizumab

Contraindications

• Ocular or periocular infections.

• Known hypersensitivity (e.g., severe intraocular inflammation) to ranibizumab or any ingredient in the formulation.

Warnings/Precautions

Endophthalmitis and Other Serious Ocular Effects

Intravitreal injections, including those with ranibizumab, associated with endophthalmitis and retinal detachments. Always use proper aseptic injection technique. (See Ophthalmic Administration under Dosage and Administration.) Monitor patients closely for signs of endophthalmitis (e.g., redness, sensitivity to light, pain, changes in vision) during the week following injection to permit early treatment. (See Advice to Patients.)

Traumatic cataract and tearing of retinal pigment epithelium also reported.

Increased IOP

Increased IOP observed both before and after (60 minutes after) intravitreal injection. Monitor IOP and perfusion of optic nerve head and manage appropriately.

Thromboembolic Events

Potential risk of arterial thromboembolic events following intravitreal injection of VEGF antagonists. Arterial thromboembolic events (i.e., nonfatal stroke, nonfatal MI, vascular death [including deaths from unknown causes]) reported at low rates (0.8–10.8%). Patients with diabetic macular edema and diabetic retinopathy had higher rates, but were typical of this patient population.

Potentially higher rate of stroke associated with the 0.5- versus 0.3-mg dose in patients with neovascular age-related macular degeneration; additional postmarketing surveillance and clinical studies are being conducted to further evaluate this finding.

Fatal Events

In clinical studies in patients with diabetic macular edema and diabetic retinopathy, fatal events occurred more frequently with ranibizumab than sham treatment. Although the fatality rate was low and included causes typical of patients with advanced diabetic complications, a potential relationship to the drug cannot be excluded.

Immunogenicity

Development of anti-ranibizumab antibodies reported. Clinical relevance unclear, but iritis or vitritis noted in some patients with neovascular age-related macular degeneration who had the highest levels of immunoreactivity.

Specific Populations

Pregnancy

Category C.

Studies not conducted in pregnant women; it is not known whether ranibizumab can cause fetal harm when administered during pregnancy. Use only if potential benefits justify potential risk to fetus. Adverse effects on embryofetal development or reproductive capacity possible due to the drug's mechanism as a VEGF antagonist.

Lactation

Not known whether ranibizumab is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established.

Adult Use

Safety and efficacy not established in adults <50 years of age.

Geriatric Use

No substantial differences in efficacy or systemic exposure (after correcting for Cl_cr) relative to younger adults.

Hepatic Impairment

Pharmacokinetics not studied; dosage adjustment not expected to be necessary.

Renal Impairment

Increased ranibizumab exposure observed in patients with renal impairment; however, changes not considered to be clinically important. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Conjunctival hemorrhage, eye pain, vitreous floaters, increased IOP, intraocular inflammation.

Drug Interactions

No formal drug interaction studies to date.

Photodynamic Therapy with Verteporfin

Serious intraocular inflammation reported; most cases occurred when ranibizumab was administered approximately 7 days after verteporfin photodynamic therapy in patients with neovascular age-related macular degeneration.

Ranibizumab Pharmacokinetics

Absorption

Bioavailability

Following monthly intravitreal injection, peak serum concentrations attained were substantially below that necessary to inhibit the biologic activity of VEGF-A by 50%. Serum concentrations predicted to be approximately 90,000 times lower than vitreal concentrations.

Peak serum concentrations predicted to be reached approximately 1 day after monthly intravitreal administration of 0.5 mg per eye.

Elimination

Half-Life

Estimated average vitreous half-life: Approximately 9 days.

Stability

Storage

Ophthalmic

2–8°C. Do not freeze; protect from light. Store in original carton until use.

Actions

• Binds to active forms of human VEGF-A, including cleaved form (VEGF₁₁₀), and inhibits their biologic activity.

• VEGF-A induces neovascularization (angiogenesis) and increases vascular permeability, which appears to play a role in the pathogenesis and progression of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

• Binding to VEGF-A prevents VEGF-A from binding to VEGF receptors (i.e., VEGFR-1, VEGFR-2) on the surface of endothelial cells, reducing endothelial cell proliferation, angiogenesis, and vascular permeability.

• Shown to reduce foveal retinal thickening and vascular permeability associated with age-related macular degeneration; however, foveal retinal thickness data did not provide information useful in influencing treatment decisions, and the area of vascular permeability was not correlated with visual acuity.

Advice to Patients

• Risk of developing endophthalmitis. Importance of patients informing ophthalmologist immediately if change in vision occurs or if treated eye becomes red, sensitive to light, or painful.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., ocular or periocular infections).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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