Ranibizumab

Ranibizumab is indicated for the treatment of patients with:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema Following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (Non Proliferative Diabetic Retinopathy (NPDR), Proliferative Diabetic Retinopathy (PDR)) in patients with Diabetic Macular Edema (DME)
• Myopic Choroidal Neovascularization (mCNV)

Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF110. VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion and is thought to contribute to pathophysiology of neovascular AMD, mCNV, DR, DME and macular edema following RVO. The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

Neovascular (Wet) Age-Related Macular Degeneration (AMD): Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the 9 months after three initial monthly doses, less frequent dosing with 4-5 doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional
average 1-2 letter gain. Patients should be assessed regularly. Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average. Patients should be assessed regularly.

Macular Edema Following Retinal Vein Occlusion (RVO): Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). In Studies RVO-1 and RVO-2, patients received monthly injections of Ranibizumab for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at Month 6 experienced on average, a loss of visual acuity at Month 7, whereas patients who were treated at Month 6 did not. Patients should be treated monthly.

Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR): Ranibizumab 0.3 mg (0.05 mL of 6 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

Myopic Choroidal Neovascularization (mCNV): Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL Ranibizumab solution) is recommended to be initially administered by intravitreal injection once a month (approximately 28 days) for up to 3 months. Patients may be retreated if needed.

Drug interaction studies have not been conducted with Ranibizumab.

Ocular or Periocular Infections: Ranibizumab is contraindicated in patients with ocular or periocular infections.

Hypersensitivity: Ranibizumab is contraindicated in patients with known hypersensitivity to ranibizumab or any of the excipients in Ranibizumab. Hypersensitivity reactions may manifest as severe intraocular inflammation.

The following adverse reactions are:

• Endophthalmitis and Retinal Detachments
• Increases in Intraocular Pressure
• Thromboembolic Events
• Fatal Events in patients with DME and DR at baseline

There are no adequate and well-controlled studies of Ranibizumab administration in pregnant women. There are no data available on the presence of ranibizumab in human milk, the effects of ranibizumab on the breastfed infant or the effects of ranibizumab on milk production/excretion.

Endophthalmitis and Retinal Detachments: Intravitreal injections, including those with Ranibizumab, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering Ranibizumab. In addition, patients should be monitored following the injection to permit early treatment should an infection occur.

Increases in Intraocular Pressure: Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with Ranibizumab. Monitor intraocular pressure prior to and following intravitreal injection with Ranibizumab and manage appropriately.

Thromboembolic Events:  Although there was a low rate of arterial thromboembolic events (ATEs) observed in the Ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).

Drugs for Age-Related Macular Degeneration (AMD)

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