INDICATIONS

FORMS

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• 90 mg (1 mL) SC q12h into the upper arm, anterior thigh or abdomen, with each injection given at a site different from the preceding injection site. Do not inject where large nerves course close to the skin, over blood vessels, into moles, scar tissue, tattoos, burn sites, or around the umbilicus.
  • Before administration, reconstitute with 1.1 mL of sterile water, resulting in a total volume of 1.2 mL.
  • Once reconstituted, it must be refrigerated and used within 24 hrs.

PEDIATRIC DOSING

RENAL DOSING

ADVERSE DRUG REACTIONS

DRUG INTERACTIONS

• Not inhibitor or inducer CYP3A4, CYP2D6, CYP1A2, CYP2C19 or CYP2E1 substrates. As expected, it does not interact with SQV, RTV, or rifampin.
• In an observational study, TPV Cmin increased by approximately. 50% with ENF co-administration.
  • Critical factors, such as food effect and adherence, are not objectively measured. The study design’s limitations could also have affected the results.
• No significant interaction with PIs, NNRTIs, NRTIs, RAL, and MVC.

RESISTANCE

• No cross-resistance with RAL, MVC, NRTIs, NNRTIs, or PIs. In vitro, clinical isolates resistant to NRTI, NNRTI, or PIs retained susceptibility to ENF.
• A 21-fold (range,

PHARMACOLOGY

COMMENTS

• Use is rare for the management of HIV in the modern ART era.
• Previously known as T-20
• Has no activity against HIV-2
• Pro:
  • Active against PI-, NNRTI-, and NRTI-resistant virus
  • Good response if background regimen includes ≥2 active ARTs
  • Well studied in ART-experienced pts
• Con:
  • Subcutaneous administration; injection site reactions
  • Time-consuming reconstitution process
  • Requires extensive patient education and training
  • Easier and more convenient alternatives are now available for most treatment-experienced pts.

References

1. Costiniuk C, Bourgault AM, Maedler-Kron C, et al. A Blast From the Past: Abdominal Wall Amyloidosis Due to Enfuvirtide Injections. Cureus. 2023;15(8):e43126.  [PMID:37692653]

   Comment: Use of the drug five years earlier (when discontinued) was implicated as a cause of drug-induced amyloidosis. This has been reported in other cases.
   

2. Clotet B, Bellos N, Molina JM, et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet. 2007;369(9568):1169-78.  [PMID:17416261]

   Comment: 61% of DRV/r-treated pts and 15% of control pts achieved >1 log reduction in VL through wk 48. VL < 50 achieved in 46% and 10% of DRV/r and control pts, respectively (p< 0.003). Darunavir-treated patients who were naive to ENF had a significantly greater VL if they included ENF in their background regimen. 21/36 achieved a VL reduction of at least 1 log, compared with only 4/35 ENF-naive pts who did not receive DRV/r.
   

3. Hicks CB, Cahn P, Cooper DA, et al. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet. 2006;368(9534):466-75.  [PMID:16890833]

   Comment: Similar to DRV studies, pts on TPV/r + an OBR that included ENF had a better virologic response rate (VL reduction of 1.67 log vs 0.98 log)
   

4. Lalezari JP, Henry K, O'Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175-85.  [PMID:12637625]

   Comment: Pooled data presented to the FDA from 2 randomized, controlled, open-label studies (TORO 1 and TORO 2) involving 995 treatment-experienced pts. ENF + an optimized background (OB) regimen is superior to the OB regimen alone. Pts had baseline VL of 5.2 logs, a mean of 12 prior ART agents, and 80-90% had >5 resistance mutations to NRTIs, NNRTIs, or PIs. VL change from baseline to wk 24 was -1.52 log for pts receiving ENF + OB regimen arm compared to -0.73 log in OB arm. As expected, pts with >2 active agents in their OB regimen are more likely to achieve undetectable VL.
   

5. 
   DHHS HIV treatment guidelines. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/archived-drugs-enfuvr... (accessed 9/1/2025, page last updated/archived 12/7/2018).
   
   
   

   Comment:
   
   Basic page, emphasizes a) must be used in combination with other ARTs, b) minimal to low placental transfer, c) no data on human teratogenicity.
   

6. Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv. Accessed (9/2/2025)

   Comment: DHHS guideline recommendations for use of enfuvirtide in pediatrics.