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| Primary information |
|---|
| ID | 10588 |
| Therapeutic ID | Th1121 |
| Protein Name | Pertuzumab |
| Sequence | >Th1121_Pertuzumab
EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
|
| Molecular Weight | 148000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 18 days |
| Description | Recombinant, humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Two heavy chains and two lights chains are composed of 448 and 214 residues respectively. FDA approved June 8, 2012. |
| Indication/Disease | Pertuzumab is indicated for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. |
| Pharmacodynamics | NA |
| Mechanism of Action | Pertuzumab is a humanized monoclonal antibody designed to bind to the HER2 receptor and inhibit the ability of HER2 to interact with other HER family members (HER1, HER2, HER3, and HER4) on the surface of cancer cells. The HER signaling pathway plays a role in the formation and growth of numerous cancers, and previous clinical trials of pertuzumab in a single agent setting had suggested clinical activity - including stable disease - in heavily pretreated patients with advanced ovarian and breast cancers. |
| Toxicity | There are no data regarding overdose of pertuzumab. Single doses higher than 25 mg/kg have not been tested.[L14747] Symptoms of overdose are likely to be consistent with pertuzumab's adverse effect profile, and may therefore involve significant diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and/or peripheral neuropathy.[L14642] Pertuzumab has been associated with the development of left ventricular dysfunction (i.e. cardiotoxicity) that may be exacerbated in instances of overdose.[L14642] |
| Metabolism | The metabolism of pertuzumab has not been studied directly. Monoclonal antibodies are typically subject to catabolism to smaller peptides and proteins prior to elimination.[L14747] |
| Absorption | Intravenously administered pertuzumab, given as a loading dose of 840mg followed by a maintenance dose of 420mg every 3 weeks, reaches steady-state concentration following the first maintenance dose.[L14747] In its subcutaneous formulation, in combination with [hylauronidase], the absolute bioavailability of pertuzumab is approximately 0.7 and the median Tmax is 4 days.[L14531] This subcutaneous formulation leverages the benefits of co-administration with hyaluronidase - this enzyme breaks down hylauronic acid, thereby decreasing the viscosity of the extracellular matrix (ECM) and allowing for greater bioavailability with subcutaneous administration.[L14531] |
| The average steady-state volume of distribution following intravenous administration is 3.53 - 7.5 L.[L14747] |
| Clearance | The median clearance of pertuzumab was determined to be 0.24 L/day based on a population pharmacokinetic analysis.[L14642] |
| Categories | Monoclonal antibodies |
| Patents Number | CA2376596 |
| Date of Issue | 10-Jun-2009 |
| Date of Expiry | 23-06-2020 |
| Drug Interaction | NA |
| Target | Receptor tyrosine-protein kinase erbB-2 |
| Brand Name | Perjeta |
| Company | Genentech |
| Brand Description | Genentech |
| Prescribed For | Neoadjuvant Treatment of Breast Cancer, Metastatic Breast Cancer (MBC), |
| Chemical Name | NA |
| Formulation | Each single use vial contains 420 mg of pertuzumab at a concentration of 30 mg/mL in 20 mM L-histidine acetate (pH 6.0), 120 mM sucrose and 0.02% polysorbate 20 |
| Physical Appearance | Sterile, clear to slightly opalescent, colorless to pale brown liquid |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The initial dose of PERJETA is 840 mg administered as a 60-minute Intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an Intravenous infusion over 30 to 60 minutes. When administered with PERJETA, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute Intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an Intravenous infusion over 30 to 90 minutes.PERJETA, trastuzumab, and docetaxel should be administered sequentially. PERJETA and trastuzumab can be given in any order. Docetaxel should be administered after PERJETA and trastuzumab. An observation period of 30 to 60 minutes is recommended after each PERJETA infusion and before commencement of any subsequent infusion of trastuzumab. |
| Contraindication | NA |
| Side Effects | Embryo-Fetal Toxicity , Left Ventricular Dysfunction , Infusion-Related Reactions, Hypersensitivity Reactions. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |