Enfuvirtide

(BAN, USAN, rINN)
Enfuvirtide Chemical formula
Synonyms: DP-178; Enfuvirtida; Enfuvirtidum; Pentafusida; Pentafuside; T-20.
Cyrillic synonym: Энфувиртид.

💊 Chemical information

Chemical formula: C204H301N51O64 = 4491.9.
CAS — 159519-65-0.
ATC — J05AX07.
ATC Vet — QJ05AX07.

💊 Adverse Effects

The most common adverse effects associated with antiretroviral regimens containing enfuvirtide are local injection site reactions with resultant pain, erythema, induration, nodules and cysts, pruritus, and ecchymosis. These reactions have been reported to occur in 98% of patients, but only a small minority needed to stop therapy. Other very common adverse effects include nausea, diarrhoea, weight loss, and peripheral neuropathy. Anorexia, abdominal pain, constipation, pancreatitis, myalgia, weakness or loss of strength, lymphadenopathy, insomnia, depression, ‘flu-like’ illness, sinusitis, and conjunctivitis are also common. An increased incidence of some bacterial infections, in particular of pneumonia, has occurred in patients receiving enfuvirtide. Hypersensitivity reactions have occurred in about 1% of patients. Other adverse effects have included anxiety, hyperglycaemia, hypertriglyceridaemia, and eosinophilia. Immune reconstitution syndrome (an inflammatory immune response resulting in clinical deterioration) has been reported during the initial phase of treatment with combination antiretroviral therapy in HIV-infected patients with severe immune deficiency. Osteonecrosis has been reported, particularly in patients with advanced HIV disease or long-term exposure to combination antiretroviral therapy.
1. Maggi P, et al. Cutaneous injection site reactions to long-term therapy with enfuvirtide. J Antimicrob Chemother 2004; 53: 678–81.

💊 Precautions

Enfuvirtide should be stopped immediately and should not be restarted in patients who develop signs of a systemic hypersensitivity reaction. An increased incidence of some bacterial infections, in particular of pneumonia, has been seen and patients receiving enfuvirtide should be closely monitored for signs of pneumonia. UK licensed product information recommends that enfuvirtide be used with caution in patients with hepatic impairment and in those with moderate to severe renal impairment. Patients co-infected with chronic hepatitis B or C and treated with combination antiretroviral therapy are at increased risk for severe and potentially fatal hepatic adverse events.

💊 Antiviral Action

Enfuvirtide is an HIV fusion inhibitor that interferes with entry of HIV into cells by binding to the gp41 subunit of the viral envelope glycoprotein, thereby inhibiting fusion of viral and cellular membranes. Strains of HIV with reduced susceptibility to enfuvirtide have been isolated in patients receiving the drug but, owing to the different mode of action of enfuvirtide and the fact that it does not require intracellular activation for its activity, cross-resistance with other antiretrovirals may occur less frequently.

Resistance.

References to the development of resistance to enfuvirtide.
1. Greenberg ML, Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 2004; 54: 333–40.

💊 Pharmacokinetics

Enfuvirtide is absorbed after subcutaneous injection with a mean absolute bioavailability of 84%. It is 92% bound to plasma proteins. Enfuvirtide is a peptide and is metabolised by hydrolysis; it does not inhibit cytochrome P450 isoenzymes. The elimination half-life is 3.8 hours after subcutaneous use, although elimination pathways have yet to be identified.
1. Patel IH, et al. Pharmacokinetics, pharmacodynamics and drug interaction potential of enfuvirtide. Clin Pharmacokinet 2005; 44: 175–86
2. Zhang X, et al. Population pharmacokinetics of enfuvirtide in HIV-1-infected pediatric patients over 48 weeks of treatment. J Clin Pharmacol 2007; 47: 510–17.

💊 Uses and Administration

Enfuvirtide is a synthetic 36-amino acid peptide that blocks HIV cell fusion and viral entry. It is used with other antiretrovirals for combination therapy of HIV infection and AIDS. Enfuvirtide is given by subcutaneous injection into the upper arm, anterior thigh, or abdomen in a usual dose of 90 mg twice daily. Each injection should be given at a different site from the preceding one. For details of doses in children and adolescents, see below.
1. Lalezari JP, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003; 348: 2175–85. Correction. ibid.; 349: 1100
2. Duffalo ML, James CW. Enfuvirtide: a novel agent for the treatment of HIV-1 infection. Ann Pharmacother 2003; 37: 1448–56
3. Oldfield V, et al. Enfuvirtide: a review of its use in the management of HIV infection. Drugs 2005; 65: 1139–60.
4. Reynes J, et al. TORO: ninety-six-week virologic and immunologic response and safety evaluation of enfuvirtide with an optimized background of antiretrovirals. AIDS Patient Care STDS 2007; 21: 533–43
5. Wiznia A, et al. T20-310 Study Group. Safety and efficacy of enfuvirtide for 48 weeks as part of an optimized antiretroviral regimen in pediatric human immunodeficiency virus 1-infected patients. Pediatr Infect Dis J 2007; 26: 799–805
6. Rockstroh J, et al. Adherence to enfuvirtide and its impact on treatment efficacy. AIDS Res Hum Retroviruses 2008; 24: 141–8
7. Saberi P, et al. Immunologic benefits of enfuvirtide in patients enrolled in a drug assistance program. Ann Pharmacother 2008; 42: 621–6.

Administration in children.

For the treatment of HIV infection, enfuvirtide may be given to children 6 to 16 years of age by subcutaneous injection into the upper arm, anterior thigh, or abdomen in a dose of 2 mg/kg twice daily (to a maximum of 90 mg twice daily). Each injection should be given at a different site from the preceding one.

💊 Preparations

Proprietary Preparations

Arg.: Fuzeon; Austral.: Fuzeon; Belg.: Fuzeon; Braz.: Fuzeon; Canad.: Fuzeon; Chile: Fuzeon; Cz.: Fuzeon; Denm.: Fuzeon; Fin.: Fuzeon; Fr.: Fuzeon; Ger.: Fuzeon; Gr.: Fuzeon; Hung.: Fuzeon; Irl.: Fuzeon; Israel: Fuzeon; Ital.: Fuzeon; Mex.: Fuzeon; Neth.: Fuzeon; Norw.: Fuzeon; NZ: Fuzeon; Pol.: Fuzeon; Port.: Fuzeon; Spain: Fuzeon; Swed.: Fuzeon; Switz.: Fuzeon; Thai.: Fuzeon; UK: Fuzeon; USA: Fuzeon.
Published November 12, 2018.