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| {{drugbox | | __NOTOC__ |
| | IUPAC_name = Acetyl-YTSLIHSLIEESQNQ QEKNEQELLELDKWASLWNWF-amide
| | {{Enfuvirtide}} |
| | width = 280
| | '''''For patient information, click <u>[[Enfuvirtide (patient information)|here]]</u>'''''. |
| | CAS_number = 159519-65-0
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| | ATC_prefix = J05
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| | ATC_suffix = AX07
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| | ATC_supplemental =
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| | PubChem = 16130199
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| | DrugBank = BTD00106
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| | C=202 | H=298 | N=50 | O=64
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| | molecular_weight = 4492.1 g/mol
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| | bioavailability = 84.3% ([[subcutaneous|SC]])
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| | protein_bound = 92%
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| | metabolism = Hepatic
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| | elimination_half-life = 3.8 hours
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| | excretion = unknown
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| | pregnancy_category = B2 <small>([[Australia|Au]])</small>, B <small>([[United States|U.S.]])</small>
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| | legal_status = S4 <small>(Au)</small>, POM <small>(UK)</small>, ℞-only <small>(U.S.)</small>
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| | routes_of_administration = [[Subcutaneous]] (SC)
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| }}
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| {{SI}}
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| | {{CMG}} |
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| ==Overview== | | ==Overview== |
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| Enfuvirtide therapy costs an estimated USD$25,000 per year in the United States. Its cost and inconvenient dosing regimen are factors behind its use as a reserve, for "salvage" therapy in patients with multi-drug resistant HIV. | | Enfuvirtide therapy costs an estimated USD$25,000 per year in the United States. Its cost and inconvenient dosing regimen are factors behind its use as a reserve, for "salvage" therapy in patients with multi-drug resistant HIV. |
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| ==Structural Formula== | | ==Category== |
| [[Acetyl|Ac]]-[[Tyrosine|Tyr]]-[[Threonine|Thr]]-[[Serine|Ser]]-[[Leucine|Leu]]-[[Isoleucine|Ile]]-[[Histidine|His]]-Ser-Leu-
| | Fusion inhibitor |
| Ile-[[Glutamic acid|Glu]]-Glu-Ser-[[Glutamine|Gln]]-[[Asparagine|Asn]]-Gln-Gln-Glu-
| | ==US Brand Names== |
| Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-
| | FUZEON<sup>®</sup> |
| Leu-Asp-Lys-[[Tryptophan|Trp]]-[[Alanine|Ala]]-Ser-Leu-Trp-[[Asparagine|Asn]]-
| | ==FDA Package Insert== |
| Trp-[[Phenylalanine|Phe]]-[[Amine|NH<sub>2</sub>]]
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| ==History==
| | ''' [[Enfuvirtide description|Description]]''' |
| Enfuvirtide originated at Duke University, where researchers formed a pharmaceutical company known as Trimeris. Trimeris began development on enfuvirtide in 1996 and initially designated it '''T-20'''. In 1999, Trimeris entered into partnership with [[Hoffmann-La Roche]] to complete the development of the drug. It was approved by the U.S. [[Food and Drug Administration]] (FDA) on March 13, 2003 as the first HIV [[fusion inhibitor]], a new class of antiretroviral drugs. It was approved on the basis of two studies (TORO 1 and TORO 2) which compared the effect of optimized regimens of antiretroviral medication with and without the addition of enfuvirtide on serum [[viral load]]. | | '''| [[Enfuvirtide clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Enfuvirtide microbiology|Microbiology]]''' |
| | '''| [[Enfuvirtide indications and usage|Indications and Usage]]''' |
| | '''| [[Enfuvirtide contraindications|Contraindications]]''' |
| | '''| [[Enfuvirtide warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Enfuvirtide adverse reactions|Adverse Reactions]]''' |
| | '''| [[Enfuvirtide drug interactions|Drug Interactions]]''' |
| | '''| [[Enfuvirtide overdosage|Overdosage]]''' |
| | '''| [[Enfuvirtide clinical studies|Clinical Studies]]''' |
| | '''| [[Enfuvirtide dosage and administration|Dosage and Administration]]''' |
| | '''| [[Enfuvirtide how supplied|How Supplied]]''' |
| | '''| [[Enfuvirtide labels and packages|Labels and Packages]]''' |
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| ==Pharmacology==
| | ==Mechanism of Action== |
| ===Mechanism of action===
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| Enfuvirtide works by disrupting the [[HIV]]-1 molecular machinery at the final stage of [[viral entry|fusion]] with the target [[Cell (biology)|cell]], preventing uninfected cells from becoming infected. A biomimetic [[peptide]], enfuvirtide was rationally designed to mimic components of the [[HIV]]-1 fusion machinery and displace them, preventing normal fusion. Drugs that disrupt fusion of [[virus]] and target [[Cell (biology)|cell]] are termed [[entry inhibitors]] or [[Fusion inhibitor]]s.
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| HIV binds to host cell receptor CD4+ by the protein GP120; upon binding, GP120 deforms allowing the viral protein GP41 to embed itself into the host cell's plasma membrane, entry inhibitors bind to GP41 preventing the creation of an entry pore for the capsid of the virus keeping it out of the cell. [http://www.roche-hiv.com/Newsandfeatures/animations/animitions_multimedia.cfm]
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| ===Microbiology===
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| Enfuvirtide is considered to be active against HIV-1 only. Low activity against HIV-2 isolates has been demonstrated ''[[in vitro]]''.<ref name="FuzeonPI">Roche Products Pty Ltd. Fuzeon (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.</ref>
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| Variable susceptibility to enfuvirtide has been observed in clinical isolates, with acquired resistance the result of a mutated 10 [[amino acid]] motif in viral gp41. Primary resistance, however, has yet to be observed.<ref name="Greenberg2004">Greenberg ML, Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 2004;54(2):333-40. PMID 15231762</ref>
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| ==Clinical use==
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| ===Indications===
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| Enfuvirtide is indicated for the treatment of HIV-1 infection, in [[combination therapy]] with other antiretrovirals, in patients where all other treatments have failed.<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
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| ===Dosage forms===
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| By virtue of its peptide nature, enfuvirtide is marketed in injectable form. The lyophilised enfuvirtide powder must be reconstituted by the patient and administered twice daily by [[subcutaneous]] injection.
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| ===Adverse effects===
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| Common [[adverse drug reaction]]s (≥1% of patients) associated with enfuvirtide therapy include: injection site reactions (pain, hardening of skin, [[erythema]], [[nodule]]s, [[cyst]]s, itch; experienced by nearly all patients, particularly in the first week), [[peripheral neuropathy]], [[insomnia]], [[clinical depression|depression]], cough, [[dyspnoea]], [[anorexia (symptom)|anorexia]], [[arthralgia]], infections (including bacterial [[pneumonia]]) and/or [[eosinophilia]]. Various [[hypersensitivity]] reactions occur infrequently (0.1–1% of patients), symptoms of which include rash, fever, nausea, vomiting, chills, rigors, [[hypotension]], elevated hepatic [[transaminase]]s; and possibly more severe reactions including [[respiratory distress]], [[glomerulonephritis]] and/or [[anaphylaxis]] – rechallenge is not recommended.<ref name="AMH2006" />
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| ==References== | | ==References== |
| {{reflist|2}} | | {{Reflist|2}} |
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| {{HIVpharm}}
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| [[Category:Entry inhibitors]]
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| [[de:Enfuvirtid]]
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| {{WH}}
| | [[Category:Fusion inhibitor]] |
| {{WikiDoc Sources}}
| | [[Category:Wikinfect]] |