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| Primary information |
|---|
| ID | 10478 |
| Therapeutic ID | Th1088 |
| Protein Name | Enfuvirtide |
| Sequence | >Th1088_Enfuvirtide
YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF
|
| Molecular Weight | 4491.876 |
| Chemical Formula | C204H301N51O64 |
| Isoelectric Point | 4.3 |
| Hydrophobicity | -0.875 |
| Melting point | NA |
| Half-life | 3.8 ± 0.6 hrs |
| Description | 36 residue, synthetically prepared peptide with N-terminal acetylation and C-terminal amidation. It blocks the fusion of HIV-1 with CD4 cells. |
| Indication/Disease | Enfuvirtide is an antiretroviral drug used in combination therapy for the treatment of HIV-1/AIDS. |
| Pharmacodynamics | NA |
| Mechanism of Action | Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes. It works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. Enfuvirtide is a biomimetic peptide that was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion. |
| Toxicity | NA |
| Metabolism | Expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool. |
| Absorption | After a 90 mg single subcutaneous injection of Enfuvirtide into the abdomen in 12 HIV-1 infected subjects, the mean peak concentration is 4.59±1.5 ug/ml and the median time to peak concentration was 8 hours (ranged from 3 to12 hours). |
| 5.5 ± 1.1 L |
| Clearance | 24.8 +/- 4.1 mL/h/kg [HIV-1 infected adult and pediatric subjects following a 90-mg single SC dose of enfuvirtide] 30.6 +/- 10.6 mL/h/kg [Following 90-mg twice daily dosing of FUZEON SC in combination with other antiretroviral agents in HIV-1 infected subjects] 40 +/- 17 mL/h/kg [pediatric patients in the presence of concomitant medications including antiretroviral agents receiving the 2 mg/kg twice daily dose] |
| Categories | Amino Acids, Peptides, and Proteins,Anti-HIV Agents,Anti-Infective Agents,Anti-Retroviral Agents,Antigens,Antigens, Viral,Antiinfectives for Systemic Use,Antiviral Agents,Antivirals for Systemic Use,Biological Factors,Cytochrome P-450 CYP2C19 Substrates,Cytochrome P-450 CYP2E1 Substrates,Cytochrome P-450 Substrates,Direct Acting Antivirals,env Gene Products, Human Immunodeficiency Virus,Fusion Protein Inhibitors,Gene Products, env,HIV Antigens,HIV Envelope Protein gp41,HIV Fusion Inhibitors,Human Immunodeficiency Virus 1 Fusion Inhibitor,Human Immunodeficiency Virus Proteins,Membrane Fusion Proteins,Membrane Proteins,Peptide Fragments,Peptides,Polyproteins,Proteins,Retroviridae Proteins,Viral Envelope Proteins,Viral Fusion Protein Inhibitors,Viral Fusion Proteins,Viral Proteins,Viral Structural Proteins |
| Patents Number | US6475491 |
| Date of Issue | 5-Nov-2002 |
| Date of Expiry | 7-Jun-2015 |
| Drug Interaction | NA |
| Target | Envelope glycoprotein |
| Brand Name | FUZEON |
| Company | Trimeris, Roche |
| Brand Description | Trimeris, Roche |
| Prescribed For | FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. |
| Chemical Name | NA |
| Formulation | Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the contents of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provide the delivery of 1 mL of the solution. Each 1 mL of the reconstituted solution contains approximately 90 mg of enfuvirtide with approximate amounts of the following excipients: 22.55 mg of mannitol, 2.39 mg of sodium carbonate (anhydrous), and sodium hydroxide and hydrochloric acid for pH adjustment as needed. The reconstituted solution has an approximate pH of 9.0 |
| Physical Appearance | White to off-white, sterile, lyophilized powder. Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the contents of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provi |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 90 mg (1 mL) twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site, and only where there is no current injection site reaction from an earlier dose. |
| Contraindication | FUZEON is contraindicated in patients with known hypersensitivity to FUZEON or any of its components |
| Side Effects | fever, chills, chest congestion, cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath; signs of a new infection such as sore throat, flu symptoms, swollen glands, easy bruising or bleeding. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |