Ranibizumab

Ranibizumab is a prescription medication for the treatment of people with wet age-related macular degeneration (wAMD, a common eye disease associated with aging), macular edema, and myopic choroidal neovascularization (mCNV). Ranibizumab is also used to treat diabetic retinopathy (DR) as well as treat diabetic macular edema (DME).

Ranibizumab belongs to a group of drugs called vascular endothelial growth factor A (VEGF-A) antagonists. It works by preventing new blood vessel growth and blood vessel leakage.

This medication comes in an injectable form to be given directly into the eye by a healthcare provider.

Common side effects of ranibizumab include eye redness and pain, and small specks in vision.

Ranibizumab comes as a liquid to be injected into the eye by a healthcare provider in a medical office, hospital, or clinic.

Before you receive a ranibizumab injection, your eye will be cleansed to prevent infection and numbed to reduce discomfort during the injection. You may feel pressure in your eye when the medication is injected. You should feel no pain.

After your injection, your doctor will need to examine your eyes before you leave the office.

You may receive a prescription for antibiotic eye drops to prevent infection after the procedure.

After receiving a ranibizumab injection, you may experience temporary vision problems. Do not drive or operate machinery until your vision has returned to normal.

Ranibizumab is usually administered by a healthcare provider in a medical setting making it unlikely for an overdose to occur. However, if overdose is suspected, seek emergency medical attention.

Administration

Ophthalmic Administration

Administer by intravitreal injection only into the affected eye(s).1

Commercially available as single-use vials containing 0.3 or 0.5 mg of the drug for intravitreal injection.1 Prior to intravitreal administration, withdraw entire contents of the appropriate strength ranibizumab vial a sterile 5-mcm, 19-gauge filter needle (provided by manufacturer) into a 1-mL tuberculin syringe using aseptic technique.1 4 Next, replace filter needle with a sterile 30-gauge, ½-inch needle (provided by manufacturer) for intravitreal injection.1 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.1

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.1

Monitor patients for elevation of IOP prior to and 30 minutes following intravitreal injection using tonometry.1 Monitoring may include evaluation of optic nerve head perfusion immediately after injection.1 Monitor patients for any manifestations of endophthalmitis.1 (See Advice to Patients.)

Each vial should be used only for treatment of a single eye.1 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.1

Dosage

Adults

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).1

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.1 14 19

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).1

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.1

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).1

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).1

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).1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

No dosage adjustment required.1 (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time.1

Contraindications

• Ocular or periocular infections.1

• Known hypersensitivity (e.g., severe intraocular inflammation) to ranibizumab or any ingredient in the formulation.1

Warnings/Precautions

Endophthalmitis and Other Serious Ocular Effects

Intravitreal injections, including those with ranibizumab, associated with endophthalmitis and retinal detachments.1 4 5 6 Always use proper aseptic injection technique.1 4 (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.1 4 (See Advice to Patients.)

Traumatic cataract and tearing of retinal pigment epithelium also reported.1 4 5

Increased IOP

Increased IOP observed both before and after (60 minutes after) intravitreal injection.1 4 6 Monitor IOP and perfusion of optic nerve head and manage appropriately.1 4

Thromboembolic Events

Potential risk of arterial thromboembolic events following intravitreal injection of VEGF antagonists.1 Arterial thromboembolic events (i.e., nonfatal stroke, nonfatal MI, vascular death [including deaths from unknown causes]) reported at low rates (0.8–10.8%).1 4 20 Patients with diabetic macular edema and diabetic retinopathy had higher rates, but were typical of this patient population.1 20

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.4 7 8 10 17

Fatal Events

In clinical studies in patients with diabetic macular edema and diabetic retinopathy, fatal events occurred more frequently with ranibizumab than sham treatment.1 4 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.1

Immunogenicity

Development of anti-ranibizumab antibodies reported.1 Clinical relevance unclear, but iritis or vitritis noted in some patients with neovascular age-related macular degeneration who had the highest levels of immunoreactivity.1

Specific Populations

Category C.1

Studies not conducted in pregnant women; it is not known whether ranibizumab can cause fetal harm when administered during pregnancy.1 Use only if potential benefits justify potential risk to fetus.1 Adverse effects on embryofetal development or reproductive capacity possible due to the drug's mechanism as a VEGF antagonist.1

Not known whether ranibizumab is distributed into milk.1 Caution if used in nursing women.1

Safety and efficacy not established.1

Safety and efficacy not established in adults <50 years of age.4

No substantial differences in efficacy or systemic exposure (after correcting for Clcr) relative to younger adults.1

Pharmacokinetics not studied; dosage adjustment not expected to be necessary.1

Increased ranibizumab exposure observed in patients with renal impairment; however, changes not considered to be clinically important.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Conjunctival hemorrhage,1 4 eye pain,1 4 vitreous floaters,1 4 increased IOP,1 4 intraocular inflammation.1 4

• If you have an allergy to ranibizumab or any other part of ranibizumab.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any kind of eye infection.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take ranibizumab with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Eyelid swelling.
• Eye discharge.
• Bleeding in the eye.
• Eye is bothered by bright light.
• Red eyes.
• The chance of heart attack or stroke due to blood clots may be raised. Call your doctor right away if you have signs of heart attack like chest pain that may spread to the arms, neck, jaw, back, or stomach; sweating that is not normal; or feeling sick or throwing up. Call your doctor right away if you have signs of stroke like change in strength on 1 side is greater than the other; eyesight, speech, or balance problems; change in thinking clearly and with logic; or very bad headache.

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

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.

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

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