Ranibizumab

S01L - Ocular vascular disorder agents ATC S01LA04 Antibody approved 2006 Parenteral Black-box warning

JFDA label: Lucentis

⚠ Black-Box Warning

Mechanism of Action

Inhibitor of Vascular endothelial growth factor A, long form — Vascular endothelial growth factor A inhibitor

Target	Action	Gene / class
Vascular endothelial growth factor A, long form efficacy	INHIBITOR	VEGFA · Secreted protein

Indications

Approved

Diabetic macular edema
Diabetic retinopathy
Macular degeneration
Macular edema
Myopic choroidal neovascularization

Contraindications

Source: Lexicomp

Additional contraindications (not in the US labeling): Active intraocular inflammation Absolute
Hypersensitivity to ranibizumab or any component of the formulation Absolute
ocular or periocular infection Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (5)

Very Common Arterial thromboembolism

Common atrial fibrillation · cerebrovascular accident · Hypertension · Peripheral edema

Nervous system disorders (4)

Very Common Foreign body sensation of eye · headache

Common migraine · Peripheral neuropathy

Renal and urinary disorders (4)

Common bacteriuria · Chronic renal failure · Renal failure · Urinary tract infection

Blood and lymphatic system disorders (1)

Very Common Anemia

Immune system disorders (2)

Common Antibody formation · seasonal allergy

Metabolism and nutrition disorders (2)

Common Diabetes mellitus · Hypercholesterolemia

Gastrointestinal disorders (6)

Common Abdominal pain · constipation · gastroesophageal reflux disease · Nausea · toothache · vomiting

Musculoskeletal and connective tissue disorders (5)

Very Common Arthralgia

Common Back pain · herniated disk · limb pain · osteoporosis

Eye disorders (11)

Very Common blurred vision · Conjunctival hemorrhage · eye pain · increased intraocular pressure · intraocular inflammation · vitreous opacity

Common conjunctivitis · eyelid edema · Punctate keratitis · Retinal degeneration · retinal hole without detachment

Infections and infestations (1)

Common Influenza

General disorders and administration site conditions (2)

Common Bleeding at injection site · Wound healing impairment

Other (15)

Very Common and vitreous detachment occurred in >10% of patients · blepharitis · but also occurred either in similar percentages to the control or more often in the control in some studies · Cataract · dry eye syndrome · eye irritation · eye pruritus · increased lacrimation · maculopathy · ocular hyperemia

Common 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 · Conjunctival hyperemia · eye discomfort · posterior capsule opacification

Respiratory, thoracic and mediastinal disorders (7)

Very Common bronchitis · Nasopharyngitis

Common chronic obstructive pulmonary disease · cough · pharyngitis · sinusitis · Upper respiratory tract infection

Dosing

Source: Lexicomp

Age-related macular degeneration (AMD), neovascular (wet): Intravitreal: 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. 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. Diabetic macular edema (DME): Intravitreal: 0.3 mg once a month (approximately every 28 days); in clinical trials, monthly doses of 0.5 mg were also studied (Massin 2010; Mitchell 2011) Diabetic retinopathy (DR): 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) Myopic choroidal neovascularization (mCNV): Intravitreal: 0.5 mg once a month (approximately every 28 days) for up to 3 months; may retreat if necessary.

Refer to adult dosing.

No dosage adjustment necessary.

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

Warnings & Precautions

Source: Lexicomp

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 and 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 is seen within 60 minutes postinjection. 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). 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.

Pregnancy & Lactation

Pregnancy

Based on its mechanism of action, adverse effects on pregnancy would be expected. Information related to use in pregnancy is limited (Jouve 2015).

Lactation

It is not known if ranibizumab is present in breast milk. The manufacturer recommends that caution be exercised when administering ranibizumab to breastfeeding women.

Monitoring

Clinical pearl	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.

Biology & Pharmacokinetics

Pharmacokinetics

Half-life	Vitreous: ~9 days

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Lucentis	Vial 10 mg/ml	1 vial	The Jordan Drugstore Co	—
Rynava	Vial 10 mg/1 ml	0.23 ml	Amman Pharmaceutical Industries Co	—
Uptera 10 mg/mL Solution for Injection	Injection 10 mg/ml	1 vial	MS PHARMA/JORDAN	—