Important note: Information in this article was accurate in May 2003. The state of the art may have changed since the publication date.
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Manufacturer: Roche and Trimeris
Formulation: Enfuvirtide is packaged in a 30-day kit containing: 60 (108 mg) single-use vials of enfuvirtide, 60 vials of sterile water for injection, 60 reconstitution syringes (3 cc), 60 administration syringes (1 cc), and alcohol wipes. The enfuvirtide kit can be stored at room temperature. However, once enfuvirtide powder has been reconstituted, it must be refrigerated and used within 24 hours.
Cost: The cost of a year’s supply of enfuvirtide is approximately $20,000.
Mechanism of Action: Enfuvirtide binds to the HR1 site in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational change required for viral fusion and entry into cells.
Drug Resistance and Cross-resistance: A 21-fold (range: <1 to 422-fold) decrease in susceptibility to enfuvirtide has been correlated with genotypic changes in gp41 amino acids 36-45 (36, 38, 40, 42, 43, and 45) (P<0.0001) [Greenberg, et al. Conf Retroviruses Opportunistic Infect. 2003 Feb 10-15;10th: Abstract No. 141]. In vitro, clinical isolates resistant to NRTI, NNRTI, or PIs retained susceptibility to enfuvirtide.
Pharmacokinetic Data
Usual Adult Dose: 90 mg (1 mL) SQ q12h into upper arm, anterior thigh or abdomen, with each injection given at a site different from the preceding injection site (prior to administration, reconstitute with 1.1 mL of sterile water for infection, giving a volume of 1.2 mL).
Pediatric Dose: Pediatric patients 6-16 years of age: 2 mg/kg (max 90 mg) SQ q12h.
Dosing with Hepatic Insufficiency: No data.
Dosing with Renal Insufficiency: Estimated CrCl >35 mL/min: 90 mg SQ q12h; CrCl <35 mL/min: No data, usual dose likely.
Drug Interactions: None. In vitro, enfuvirtide did not inhibit or induce the metabolism of CYP3A4, CYP2D6, CYP1A2, CYP2C19 or CYP2E1 substrates. Does not interact with SQV/r, RTV, or rifampin [Boyd, et al. Conf Retroviruses Opportunistic Infect. 2003 Feb 10-15;10th: Abstract No. 541].
Adverse Drug Reactions (ADRs)
Pregnancy/Breastfeeding Risks
Category B. Not teratogenic in animal studies. No human data. Breastfeeding not recommended.
Clinical Trial Information: The potency and efficacy of ENF was demonstrated in TORO 1, conducted in North America and Brazil, and TORO 2, conducted in Europe and Australia. In these trials highly treatment experienced patients failing HAART were randomized in a 2:1 fashion to take ENF plus an optimized background regimen, chosen based on treatment history and the results of genotypic and phenotypic resistance tests, versus the optimized background regimen alone. Patients had a baseline viral load of 5.2 log10 c/mL, had received a mean of 12 prior antiretroviral agents, and 80% to 90% had >5 resistance mutations to NRTIs, NNRTIs, or PIs. As discussed in a previous issue of The Hopkins HIV Report [see Gallant, HHR 2002;14(5):1], patients in the ENF arm experienced a greater decline in viral load and were more likely to achieve viral suppression. The viral load change from baseline to week 24 was -1.52 log10 c/mL for patients in the ENF plus background regimen arm compared to -0.73 log10 c/mL for patients receiving only the background regimen (P<0.0001). Response to both regimens varied based on the antiviral activity of the drugs used in the background regimen: Those whose regimen included more active drugs, as determined by baseline genotypic and phenotypic data, had better responses to both arms, though ENF recipients had significantly better responses in all cases except those few in whom the background regimen contained at least 5 active drugs. [Henry, et al. Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr19B; Clotet, et al. Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr19A].
Package Insert: The complete package insert is available online at http://www.Fuzeon.com.
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