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| Primary information |
|---|
| ID | 10499 |
| Therapeutic ID | Th1095 |
| Protein Name | Ranibizumab |
| Sequence | >Th1095_Ranibizumab
EVQLVESGGGLVQPGGSLRLSCAASGYDFTHYGMNWVRQAPGKGLEWVGWINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPYYYGTSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL
|
| Molecular Weight | 48349.61 |
| Chemical Formula | C2158H3282N562O681S12 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Approximately 9 days. |
| Description | Recombinant (E.coli derived), humanized IgG1 kappa isotype monoclonal antibody (intraocular use). It binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). Ranibizumab is marketed under the name Lucentis. |
| Indication/Disease | For the treatment of patients with macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema. |
| Pharmacodynamics | Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab is a VEGF-A antagonist that binds to and inhibits the biologic activity of active forms of human VEGF-A, including the cleaved form (VEGF110). VEGF-A has been shown to cause neovascularization (angiogenesis) and an increase in vascular permeability, which is thought to contribute to the progression of the neovascular form of age-related macular degeneration (AMD). |
| Mechanism of Action | Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, (VEGF110). 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. |
| Toxicity | There is no information available regarding the LD50 values of ranibizumab. There is also limited clinical experience of ranibizumab overdose: concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients, with no additional unexpected adverse reactions that were observed |
| Metabolism | The metabolism of ranibizumab has not been studied. Since it is a monoclonal antibody fragment, ranibizumab is expected to undergo catabolism. |
| Absorption | Ranibizumab rapidly penetrates through the retina to reach the choroid after intravitreal injection. Following monthly intravitreal administration of 0.5 mg ranibizumab in patients with neovascular (wet) age-related macular degeneration, the mean Cmax (±SD) was 1.7 (± 1.1) ng/mL. Following an implant insertion, the mean (±SD) Cmax of ranibizumab was 0.48 (±0.17) ng/mL and median Tmax was 26 days, with a range of one to 89 days. |
| The apparent volume of the central compartment (Vd/F) is 2.77 L. Ranibizumab is not shown to accumulate in serum. Due to its small size from lacking the Fc region of an antibody, ranibizumab achieves enhanced diffusion into the retina and choroid |
| Clearance | In patients with retinal vein occlusion or diabetic macular edema, the apparent clearance (CL/F) of ranibizumab was 24.8 L/day. |
| Categories | Amino Acids, Peptides, and Proteins,Angiogenesis Inhibitors,Angiogenesis Modulating Agents,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Antineovascularisation Agents,Blood Proteins,EENT Drugs, Miscellaneous,Globulins,Growth Inhibitors,Growth Substances,Immunoglobulins,Immunoproteins,Ocular Vascular Disorder Agents,Ophthalmics,Ophthalmologicals,Proteins,Sensory Organs,Serum Globulins,Vascular Endothelial Growth Factor Inhibitor,Vascular Endothelial Growth Factor Inhibitors |
| Patents Number | CA2286330 |
| Date of Issue | 10-Jun-2008 |
| Date of Expiry | 3-Apr-2018 |
| Drug Interaction | NA |
| Target | Vascular endothelial growth factor A |
| Brand Name | Lucentis |
| Company | Genentech |
| Brand Description | Genentech |
| Prescribed For | 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) |
| Chemical Name | NA |
| Formulation | supplied as a preservative-free, sterile solution in a single-use glass vial designed to deliver 0.05 mL of 10 mg/mL LUCENTIS (0.5 mg dose vial) or 6 mg/mL LUCENTIS (0.3 mg dose vial) aqueous solution with 10 mM histidine HCl, 10% α,α-trehalose dihydrate, 0.01% polysorbate 20, pH 5.5. |
| Physical Appearance | Sterile, colorless to pale yellow solution in a single-use glass vial |
| Route of Administration | Intravitreal Injection ONLY |
| Recommended Dosage | Neovascular (Wet) Age-Related Macular Degeneration (AMD): LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Diabetic Macular Edema (DME): LUCENTIS 0.3 mg (0.05 mL of 6 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).; Diabetic Retinopathy In Patients With Diabetic Macular Edema: LUCENTIS 0.3 mg (0.05 mL of 6 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). |
| Contraindication | Ocular Or Periocular Infections LUCENTIS is contraindicated in patients with ocular or periocular infections. Hypersensitivity to ranibizumab or any of the excipients in LUCENTIS. Hypersensitivity reactions may manifest as severe intraocular inflammation. |
| Side Effects | Endophthalmitis and Retinal Detachments Increases in Intraocular Pressure, Thromboembolic Events, Fatal Events in patients with DME and DR at baseline. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |