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Ranibizumab

Pronunciation

(ra ni BIZ oo mab)

Index Terms

  • rhuFabV2

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intraocular [preservative free]:

Lucentis: 0.3 mg/0.05 mL (0.05 mL); 0.5 mg/0.05 mL (0.05 mL)

Brand Names: U.S.

  • Lucentis

Pharmacologic Category

  • Angiogenesis Inhibitor
  • Monoclonal Antibody
  • Ophthalmic Agent
  • Vascular Endothelial Growth Factor (VEGF) Inhibitor

Pharmacology

Ranibizumab is a recombinant humanized monoclonal antibody fragment which binds to and inhibits human vascular endothelial growth factor A (VEGF-A). Ranibizumab inhibits VEGF from binding to its receptors and thereby suppressing neovascularization and slowing vision loss.

Absorption

Low levels are detected in the serum following intravitreal injection.

Half-Life Elimination

Vitreous: ~9 days

Use: Labeled Indications

Diabetic retinopathy: Treatment of diabetic retinopathy (nonproliferative diabetic retinopathy [NPDR]), proliferative diabetic retinopathy [PDR]) in patients with diabetic macular edema (DME)

Macular degeneration: Treatment of neovascular (wet) age-related macular degeneration (AMD)

Macular edema: Treatment of macular edema following retinal vein occlusion (RVO); diabetic macular edema (DME)

Choroidal neovascularization secondary to pathologic myopia: Canadian labeling: Additional use (not in US labeling): Treatment of visual impairment due to choroidal neovascularization (CNV) secondary to pathologic myopia

Contraindications

Hypersensitivity to ranibizumab or any component of the formulation; ocular or periocular infection

Canadian labeling: Additional contraindications (not in U.S. labeling): Active intraocular inflammation

Dosing: Adult

Age-related macular degeneration (AMD): Intravitreal:

U.S. labeling: 0.5 mg once a month (approximately every 28 days). Frequency may be reduced (eg, 4 to 5 injections over 9 months) after the first 3 injections or may be reduced after the first 4 injections to once every 3 months if monthly injections are not feasible.

Canadian labeling: 0.5 mg once a month. Frequency may be reduced after the first 3 injections to once every 3 months if monthly injections are not feasible.

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

Choroidal neovascularization secondary to pathologic myopia: Intravitreal: Canadian labeling: Initial: 0.5 mg; may repeat 0.5 mg dose at monthly intervals if clinically indicated.

Diabetic macular edema (DME): Intravitreal:

U.S. labeling: 0.3 mg once a month (approximately every 28 days)

Canadian labeling: 0.5 mg once a month until achievement of stable visual acuity for 3 consecutive months. Upon discontinuation, may resume monthly therapy if monitoring identifies a loss of visual acuity.

Diabetic retinopathy (DR): Adults: Intravitreal: 0.3 mg once a month (approximately every 28 days)

Macular edema following retinal vein occlusion (RVO): Intravitreal: 0.5 mg once a month (approximately every 28 days). Note: Canadian labeling recommends continuing therapy until achievement of stable visual acuity for 3 consecutive months; upon discontinuation, may resume monthly therapy if monitoring identifies a loss of visual acuity.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. However, significant systemic exposure is not expected.

Administration

For ophthalmic intravitreal injection only. Remove contents from vial using a 5 micron 19-gauge filter needle attached to a tuberculin syringe. Discard filter needle and replace with a sterile 30 gauge 1/2 inch needle for injection (do not use filter needle for intravitreal injection). Adequate anesthesia and a topical broad-spectrum antimicrobial agent should be administered prior to the procedure. Canadian labeling recommends administering ranibizumab at least 30 minutes after laser photocoagulation therapy when administered on the same day.

Storage

Store in original carton under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. Do not freeze.

Drug Interactions

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Adverse Reactions

As reported with AMD, RVO, and DME studies:

>10%:

Cardiovascular: Arterial thromboembolism (AMD trials during first year: 2%; DME trials at 3 years: 11%)

Central nervous system: Foreign body sensation of eye (7% to 16%), headache (6% to 12%)

Hematologic & oncologic: Anemia (4% to 11%)

Neuromuscular & skeletal: Arthralgia (2% to 11%)

Ophthalmic: Conjunctival hemorrhage (47% to 74%), eye pain (17% to 35%), vitreous opacity (7% to 27%), increased intraocular pressure (7% to 24%), blurred vision (5% to 18%), intraocular inflammation (1% to 18%)

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 (5% to 16%), bronchitis (6% to 11%)

1% to 10%:

Cardiovascular: Peripheral edema (6%), atrial fibrillation (1% to 5%), cerebrovascular accident (AMD trials during 2 years: 3%; DME trials at 3 years: 2%)

Central nervous system: Peripheral neuropathy (1% to 5%)

Endocrine & metabolic: Hypercholesterolemia (3% to 7%)

Gastrointestinal: Nausea (9% to 10%), constipation (8%), gastroesophageal reflux disease (1% to 6%)

Genitourinary: Chronic renal failure (6%)

Immunologic: Antibody formation (1% to 9%), seasonal allergy (8%)

Infection: Influenza (3% to 7%)

Local: Bleeding at injection site (1% to 5%)

Ophthalmic: Retinal degeneration (1% to 8%)

Note: Conjunctival hyperemia, eye discomfort, posterior capsule opacification, and retinopathy occurred in 1% to 10% of patients, but also occurred in similar percentages to the control or more often in the control in some of the studies.

Renal: Renal failure (7%)

Respiratory: Upper respiratory tract infection (9%), cough (5% to 9%), sinusitis (3% to 8%), chronic obstructive pulmonary disease (3% to 6%)

Miscellaneous: Wound healing impairment (1%)

All indications: <1% (Limited to important or life-threatening): Anterior chamber inflammation, corneal edema, corneal erosion, coronary artery occlusion, decreased visual acuity, endophthalmitis, epithelial keratopathy, eye discharge (lid margin), hypoglycemia, iatrogenic traumatic cataracts, intestinal obstruction, photophobia, retinal pigment epithelium tear, rhegmatogenous retinal detachments, urticaria

As reported with choroidal neovascularization secondary to pathologic myopia (not in U.S. labeling):

>10%:

Ophthalmic: Conjunctival hemorrhage (11%)

Respiratory: Nasopharyngitis (11%)

1% to 10%:

Cardiovascular: Hypertension (3%)

Central nervous system: Headache (8%), migraine (2%)

Endocrine & metabolic: Diabetes mellitus (2%)

Gastrointestinal: Abdominal pain (3%), nausea (2%), toothache (2%), vomiting (2%)

Genitourinary: Urinary tract infection (3%), bacteriuria (2%)

Infection: Influenza (2%)

Local: Bleeding at injection site (4%)

Neuromuscular & skeletal: Back pain (2%), herniated disk (2%), limb pain (2%), osteoporosis (2%)

Ophthalmic: Punctate keratitis (8%), vitreous opacity (5%), dry eye syndrome (4%), eye pain (4%), increased intraocular pressure (3%), blepharitis (2%), conjunctivitis (2%), eyelid edema (2%), retinal hole without detachment (2%)

Respiratory: Upper respiratory tract infection (3%), pharyngitis (2%)

<1% (Limited to important or life-threatening): Cataract, conjunctival edema, corneal erosion, hepatic insufficiency, hypercholesterolemia, hypersensitivity, increased intracranial pressure, iridocyclitis, ocular hyperemia, retinal hemorrhage, sciatica, tendonitis, uveitis, viral conjunctivitis (adenovirus), vitreous detachment

Warnings/Precautions

Concerns related to adverse effects:

• Endophthalmitis/retinal detachment: Intravitreous injections may be associated with endophthalmitis and retinal detachments. Proper aseptic injection techniques should be used. Patients should be monitored for potential infection following the injection and instructed to report any signs of infection (eg, eye pain or redness, photophobia, blurred vision) immediately.

• Hypersensitivity reactions: Hypersensitivity may present as severe intraocular inflammation; instruct patients to report intraocular inflammation that increases with severity. Rare hypersensitivity reactions (including anaphylaxis) have been associated with another VEGF inhibitor, pegaptanib, occurring within several hours of use; monitor closely. Equipment and appropriate personnel should be available for monitoring and treatment of anaphylaxis.

• Increased intraocular pressure: Prior to and following intravitreal injection, intraocular pressure may increase. Onset postinjection is seen within 60 minutes. Monitor intraocular pressure before and after injection and manage accordingly.

• Thromboembolic events: Risk of thromboembolic events, particularly stroke, may be increased following intravitreal administration of VEGF inhibitors. Use caution in patients with known risk factors (eg, history of stroke, TIA)

• Visual disturbances: Intravitreal injections of ranibizumab may induce temporary visual disturbances that impair the ability to drive or operate machinery. Affected patients should be advised to abstain from driving or using machinery until resolution of visual disturbances.

Disease-related concerns:

• Diabetic macular edema (DME) and diabetic retinopathy (DR): Pooled analysis of trials involving DME and DR patients revealed a higher incidence of fatal events in patients treated with ranibizumab compared to control (3% in patients treated with 0.3 mg in the first 2 years compared to 1% in the control). Overall, the incidence of fatalities was consistent with deaths normally observed in patients with advanced diabetic complications; however, a potential association between fatal events and intravitreal administration of VEGF inhibitors cannot be excluded.

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 first week following injection); retinal perfusion, endophthalmitis; visual acuity

In the treatment of CNV secondary to PM, the Canadian labeling recommends monthly monitoring (eg, clinical evaluation, fluorescein angiography, optical coherence tomography) for disease activity for the first two months and at least every 3 months thereafter for the first year. Subsequent monitoring is at the physician’s discretion.

Pregnancy Considerations

Based on its mechanism of action, adverse effects on pregnancy would be expected. Canadian labeling recommends that women of childbearing potential use effective contraception during therapy and to wait 3 months after therapy before trying to conceive.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience xerophthalmia, floaters, or foreign body sensation of eye. Have patient report immediately to prescriber strength differences from one side to another, difficulty speaking or thinking, change in balance, blurred vision, angina, edema of extremities, painful extremities, vision changes, ophthalmalgia, severe eye irritation, eyelid edema, eye discharge, subconjunctival hemorrhage, or sensitivity to light (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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