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AIDS ANTIVIRAL FUSION INHIBITORS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) HIV fusion inhibitors are a newer class of AIDS antiviral drugs with a mechanism involving prevention of formation of an envelope glycoprotein structure required for fusion. These drugs inhibit the HIV-1 virus from binding to, entering, and infecting healthy cells. They block cell fusion and viral entry. Fusion of a viral envelope with a target cell membrane is required for the initiation of infections, and thus, virus replication.

Specific Substances

    A) GENERAL TERMS
    1) Antiviral fusion inhibitors, AIDS
    2) Fusion inhibitors, AIDS
    3) HIV, AIDS antiviral fusion inhibitors
    ENFUVIRTIDE
    1) Pentafuside
    2) DP-178
    3) T-20
    4) CAS 159519-65-0

    1.2.1) MOLECULAR FORMULA
    1) Enfuvirtide: C204-H301-N51-O64 (Prod Info FUZEON(R) subcutaneous injection, 2011)

Available Forms Sources

    A) FORMS
    1) Enfuvirtide is available as a sterile, lyophilized powder containing 108 mg of enfuvirtide (delivering 90 mg/mL when reconstituted with 1.1 mL of sterile water for injection) for subcutaneous injection (Prod Info FUZEON(R) subcutaneous injection, 2011).
    B) USES
    1) Enfuvirtide is used in combination with other agents to treat HIV-1 infections in treatment-experienced patients with evidence of HIV-1 replication (Prod Info FUZEON(R) subcutaneous injection, 2011).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Enfuvirtide is used in combination with other agents to treat HIV-1 infections in treatment-experienced patients with evidence of HIV-1 replication.
    B) PHARMACOLOGY: Enfuvirtide, a fusion inhibitor, prevents viral fusion and entry of HIV-1 into cells by binding to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Injection site reactions (eg, erythema, induration, and pain), nausea, diarrhea, fatigue, headache, dizziness, lymph node tenderness, weight loss, sinusitis, cough, pancreatitis, and myalgias have been reported in clinical trials with enfuvirtide therapy.
    E) WITH POISONING/EXPOSURE
    1) At the time of this review, there are no acute overdose data available. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
    0.2.20) REPRODUCTIVE
    A) Enfuvirtide is classified as FDA pregnancy category B. No human studies have been performed to assess the effects of enfuvirtide on human pregnancy or lactation. Animal studies in rats and rabbits demonstrated no fetal harm due to enfuvirtide use during pregnancy. In animal lactation studies, radioactivity was present in the milk of lactating rats after administration of radio-labeled 3H-enfuvirtide.

Laboratory Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) Monitor dermal injection sites for irritation or hypersensitivity reactions.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea. As these agents are generally given in conjunction with other HIV antiretroviral agents, it would be advisable to monitor for overdoses from these agents as well.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Severe toxicity is not expected after an overdose.
    C) DECONTAMINATION
    1) Gastrointestinal decontamination is not recommended; administered via the parenteral route.
    D) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary unless other toxic agents have been administered concurrently.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) Hemodialysis is NOT expected to significantly enhance the clearance of enfuvirtide due to extensive protein binding and large volume of distribution.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Symptomatic patients should be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered. Symptoms of overdose are similar to reported side effects of the medication.
    I) PHARMACOKINETICS
    1) Following 90-mg twice daily: Tmax: 4 hours (range, 4 to 8 hr); Cmax: 5 +/- 1.7 mcg/mL. Absolute bioavailability: 84.3% +/- 15.5%. Protein binding: approximately 92%. Vd: 5.5 +/- 1.1 L. Mean elimination half-life: 3.8 +/- 0.6 hours.
    J) DIFFERENTIAL DIAGNOSIS
    1) Other AIDS agents; symptoms from AIDS.

Range Of Toxicity

    A) TOXICITY: A specific toxic dose has not been established. During a clinical trial, the highest enfuvirtide dose administered to 12 patients was 180 mg SubQ as a single dose. There were no adverse effects reported.
    B) THERAPEUTIC DOSE: ADULTS AND CHILDREN OLDER THAN 16 YEARS OF AGE: 90 mg (1 mL) subQ twice a day. CHILDREN 6 TO 16 YEARS OF AGE AND OLDER: 2 mg/kg subQ twice a day; maximum dose of 90 mg twice daily; (less than 6 years of age): safety and efficacy not established in pediatric patients less than 6 years of age.

Clinical Effects

Summary Of Exposure

    A) USES: Enfuvirtide is used in combination with other agents to treat HIV-1 infections in treatment-experienced patients with evidence of HIV-1 replication.
    B) PHARMACOLOGY: Enfuvirtide, a fusion inhibitor, prevents viral fusion and entry of HIV-1 into cells by binding to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Injection site reactions (eg, erythema, induration, and pain), nausea, diarrhea, fatigue, headache, dizziness, lymph node tenderness, weight loss, sinusitis, cough, pancreatitis, and myalgias have been reported in clinical trials with enfuvirtide therapy.
    E) WITH POISONING/EXPOSURE
    1) At the time of this review, there are no acute overdose data available. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.

Heent

    3.4.5) NOSE
    A) WITH THERAPEUTIC USE
    1) SINUSITIS: During phase 3 clinical trials, 6% of patients (n=663) taking enfuvirtide in addition to a background regimen of other antiretroviral drugs experienced sinusitis. This corresponds to a rate of 7.2 events per 100 patient-years as compared with 4.9 events per 100 patient-years in patients who were only taking the antiretroviral background regimen (n=334) (Prod Info FUZEON(R) subcutaneous injection, 2011).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) SINUSITIS
    1) WITH THERAPEUTIC USE
    a) In phase 3 clinical trials of patients treated with enfuvirtide plus a background antiretroviral regimen (n=663) or a background regimen alone (n=334) for 48 weeks, sinusitis was reported more frequently in patients receiving enfuvirtide/background regimen (6%; 7.2 events/100 patient-years) compared with those receiving the background regimen alone (4.9 events/100 patient-years) (Prod Info FUZEON(R) subcutaneous injection, 2011).
    B) COUGH
    1) WITH THERAPEUTIC USE
    a) In phase 3 clinical trials of patients treated with enfuvirtide plus a background antiretroviral regimen (n=663) or a background regimen alone (n=334) for 48 weeks, cough was reported more frequently in patients receiving enfuvirtide/background regimen (3.9%; 4.7 events/100 patient-years) compared with those receiving the background regimen alone (2.5 events/100 patient-years) (Prod Info FUZEON(R) subcutaneous injection, 2011).
    C) PNEUMONIA
    1) WITH THERAPEUTIC USE
    a) During phase 3 clinical trials, the incidence of bacterial pneumonia in patients given enfuvirtide was 6.9%. This correlates to 6.7 pneumonia events per 100 patient-years as compared with 0.6 events per 100 patient-years in the control group. However, the causal relationship between the administration of enfuvirtide and the development of pneumonia has not been definitively established (Prod Info FUZEON(R) subcutaneous injection, 2011).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Mild to moderate headaches were reported in some patients in a clinical study ((Anon, 200a)). A direct causal relationship was not established.
    B) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Dizziness has been reported in some patients in a clinical trial ((Anon, 200a)). A direct causal relationship was not established.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) WEIGHT LOSS FINDING
    1) WITH THERAPEUTIC USE
    a) During phase 3 clinical trials, 6.6% of patients (n=663) taking enfuvirtide in addition to a background regimen of other antiretroviral drugs experienced a decrease in weight. This corresponds to a rate of 7.9 events per 100 patient-years as compared with 6.2 events per 100 patient-years in patients who were only taking the antiretroviral background regimen (n=334) (Prod Info FUZEON(R) subcutaneous injection, 2011).
    B) PANCREATITIS
    1) WITH THERAPEUTIC USE
    a) During phase 3 clinical trials, 3% of patients (n=663) taking enfuvirtide in addition to a background regimen of other antiretroviral drugs developed pancreatitis. This corresponds to a rate of 3.6 events per 100 patient-years as compared with 2.5 events per 100 patient-years in patients who were only taking the antiretroviral background regimen (n=334) (Prod Info FUZEON(R) subcutaneous injection, 2011).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) INJECTION SITE REACTION
    1) WITH THERAPEUTIC USE
    a) Erythema, induration, and pain at the subcutaneous injection site (injection or infusion), usually mild or moderate, were observed in the majority of patients during clinical trials (Prod Info FUZEON(R) subcutaneous injection, 2011; Anon, 1999).
    b) Grade 3 and 4 injection site reactions including induration (39% and 18%, respectively), erythema (22% and 10%, respectively), nodules and cysts (23% and 0.2%, respectively), and ecchymosis (5% and 2%, respectively) and grade 3 pain and discomfort (11%) and pruritus (3%) have been reported in phase 3 clinical trials of patients treated with enfuvirtide (n=663) for 48 weeks (Prod Info FUZEON(R) subcutaneous injection, 2011).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) During phase 3 clinical trials, 2.7% of patients (n=663) taking enfuvirtide in addition to a background regimen of other antiretroviral drugs experienced myalgias. This corresponds to a rate of 3.2 events per 100 patient-years as compared with 1.2 events per 100 patient-years in patients who were only taking the antiretroviral background regimen (n=334) (Prod Info FUZEON(R) subcutaneous injection, 2011).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LYMPHEDEMA
    1) WITH THERAPEUTIC USE
    a) Lymph node tenderness and swelling has been reported in clinical trials following injections of enfuvirtide ((Anon, 200a)).

Reproductive

    3.20.1) SUMMARY
    A) Enfuvirtide is classified as FDA pregnancy category B. No human studies have been performed to assess the effects of enfuvirtide on human pregnancy or lactation. Animal studies in rats and rabbits demonstrated no fetal harm due to enfuvirtide use during pregnancy. In animal lactation studies, radioactivity was present in the milk of lactating rats after administration of radio-labeled 3H-enfuvirtide.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) CASE REPORT: No teratogenic effects were found in the infant of a multidrug-resistant, HIV-1-positive woman following tipranavir and enfuvirtide therapy during the third trimester of pregnancy, although maternal hepatotoxicity was noted. A 34-year-old woman treated for 2 years with antiretroviral therapy regimens (including ritonavir-boosted lopinavir and later, zidovudine, lamivudine, and nevirapine) was switched at 28 weeks gestation to zidovudine, lamivudine, tenofovir, ritonavir-boosted tipranavir and enfuvirtide therapy following a viral load increase to 28,600 copies/mL and the detection of NRTI and NNRTI mutations. The viral load had decreased to 503 copies/mL by delivery at 37 weeks gestation. While no enfuvirtide was detected in cord blood, the tipranavir area under the curve at 12 hours measured 44.5 mcg/mL x hour, with a ratio of cord blood to material blood of 0.41 (15.6 and 36.8 mcg/mL, respectively). The 2740 g female infant was delivered via emergency cesarean section in response to fetal distress (cause undetermined). She was briefly intubated and received surfactant and packed erythrocytes to treat meconium aspiration and anemia. The mother had developed grade 4 hepatotoxicity (AST 883 units/L), which subsided after delivery with no further treatment. Following a 4-week course of zidovudine, the infant had repeatedly tested negative for HIV by her 12-month follow-up (Weizsaecker et al, 2011).
    B) ANIMAL STUDIES
    1) Animal studies in rats and rabbits at enfuvirtide doses up to 27 times and 3.2 times the adult human dose on a m(2) basis, respectively, have shown no evidence of harm to the fetus following maternal administration (Prod Info FUZEON(R) subcutaneous injection, 2008).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy in humans (Prod Info FUZEON(R) subcutaneous injection, 2008). In general, women who are receiving combination antiretroviral therapy (ART) for HIV infection when pregnancy is discovered should continue their regimen, while being monitored for complications and toxicities. Women who do not require ART for their own health should receive ART (3-drug regimen) for prophylaxis of perinatal transmission. An Antiretroviral Pregnancy Registry has been established, and prescribers can register patients by calling 1-800-258-4263 (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012).
    B) PREGNANCY CATEGORY
    1) Enfuvirtide is classified by the manufacturer as FDA pregnancy category B (Prod Info FUZEON(R) subcutaneous injection, 2008).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info FUZEON(R) subcutaneous injection, 2008). Due to the risk of postnatal transmission of HIV, the Centers for Disease Control and Prevention does not recommend breastfeeding for HIV-infected mothers, including those who are receiving combination antiretroviral therapy or prophylaxis (Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, 2012).
    B) ANIMAL STUDIES
    1) In animal studies, radioactivity was present in the milk of lactating rats after administration of radio-labeled 3H-enfuvirtide. The radioactivity in the milk may have been from the radio-labeled enfuvirtide or from radio-labeled enfuvirtide metabolites (ie, amino acids and peptide fragments) (Prod Info FUZEON(R) subcutaneous injection, 2008).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) There was no impairment of fertility in male and female rats who were given enfuvirtide at doses up to 1.6 times the maximum recommended adult human daily dose on a m(2) basis (Prod Info FUZEON(R) subcutaneous injection, 2008).

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) LACK OF INFORMATION
    1) ENFUVIRTIDE - Long-term animal carcinogenicity studies have not been conducted (Prod Info FUZEON(R) subcutaneous injection, 2007).

Genotoxicity

    A) According to a series of in vivo and in vitro assays, including the Ames bacterial reverse mutation assay, a mammalian cell forward gene mutation assay in AS52 Chinese Hamster ovary cells, and a mouse micronucleus assay, enfuvirtide was neither mutagenic or clastogenic (Prod Info FUZEON(R) subcutaneous injection, 2007).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) Monitor dermal injection sites for irritation or hypersensitivity reactions.

Methods

    A) CHROMATOGRAPHY
    1) A reversed phase HPLC and fluorescence method for detection and quantification of pentafuside from human plasma has been described (Lawless et al, 1998).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Symptomatic patients should be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged.

Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) Monitor dermal injection sites for irritation or hypersensitivity reactions.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is not recommended; administered via the parenteral route.

Range Of Toxicity

Summary

    A) TOXICITY: A specific toxic dose has not been established. During a clinical trial, the highest enfuvirtide dose administered to 12 patients was 180 mg SubQ as a single dose. There were no adverse effects reported.
    B) THERAPEUTIC DOSE: ADULTS AND CHILDREN OLDER THAN 16 YEARS OF AGE: 90 mg (1 mL) subQ twice a day. CHILDREN 6 TO 16 YEARS OF AGE AND OLDER: 2 mg/kg subQ twice a day; maximum dose of 90 mg twice daily; (less than 6 years of age): safety and efficacy not established in pediatric patients less than 6 years of age.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) ENFUVIRTIDE
    a) SUBCUTANEOUS
    1) The recommended dose of enfuvirtide is 90 milligrams (1 milliliter) subcutaneously administered twice daily into the upper arm, anterior thigh, or abdomen, with each injection administered at a different site from the preceding injection site (Prod Info FUZEON(R) subcutaneous injection, 2007).
    2) In an ongoing study (as yet unpublished) assessing three different doses of enfuvirtide in combination with abacavir, amprenavir, and efavirenz in HIV-1 infected adults, subcutaneous injections of 50 milligrams twice daily, 75 milligrams twice daily, or 100 milligrams twice daily have been used ((Anon, 2000)).
    3) SUBCUTANEOUS INFUSION - It is anticipated that enfuvirtide will be targeted for dispensing as a continuous subcutaneous infusion via a portable infusion pump (James, 1998).
    b) INTRAVENOUS
    1) A dose of 100 milligrams twice daily has been effective in reducing viral load to undetectable levels in human immunodeficiency virus (HIV)-infected patients ((Saag, 1997)). This regimen may be impractical for clinical use.
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) ENFUVIRTIDE
    a) Children 6 to 16 years of age - The recommended dose is 2 milligrams/kilogram administered subcutaneously twice daily into the upper arm, anterior thigh, or abdomen, with each injection administered at a different site from the preceding injection site (Prod Info FUZEON(R) subcutaneous injection, 2007).
    b) Children less than 6 years of age - Safety and efficacy have not been established (Prod Info FUZEON(R) subcutaneous injection, 2007).
    c) In clinical trials, enfuvirtide has been given as subcutaneous or intravenous infusions at doses of 15 milligrams/square meter, 30 milligrams/square meter, or 60 milligrams/square meter, followed by 12 hour pyruvate kinase (PK) in all dose ranges for a duration of 24 to 48 weeks (Anon, 2000c).

Maximum Tolerated Exposure

    A) A specific toxic dose has not been established. During a clinical trial, the highest enfuvirtide dose administered to 12 patients was 180 mg SubQ as a single dose. There were no adverse effects reported (Prod Info FUZEON(R) subcutaneous injection, 2011).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) Therapeutic drug concentration for HIV infection is not yet established for enfuvirtide.
    a) In vitro, concentrations required for 50% inhibition of virus-mediated cell-to-cell fusion and HIV-1 infection of T-cells were 1 ng/mL and 80 ng/mL, respectively (Wild et al, 1994). Investigations correlating clinical efficacy with plasma concentrations have not been performed.
    b) The 50% inhibitory concentration was noted in one in vitro study, using the 14aPre strain of HIV-1 virus, to be 100 ng/mL (0.10 microgram/mL) (Tremblay et al, 2000). The 50% inhibitory concentration was found in another in vitro study to vary, depending on the virus strain, by a factor up to log(10) (Derdeyn et al, 2000).
    c) Synergism was observed when combined with the chemokine receptor inhibitor AMD-3100 (Tremblay et al, 2000).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Enfuvirtide is a human immunodeficiency virus (HIV) fusion inhibitor given for the treatment of HIV infection (Wild et al, 1994; (p 115). It is a synthetic peptide, derived from the highly conserved sequences within the HIV-1 transmembrane fusion protein gp41. It prevents viral fusion and entry into cells by binding to one of two peptide domains within gp41 of the virus, blocking the peptide ability to form a natural coil structure (Prod Info FUZEON(R) subcutaneous injection, 2007; Lambert et al, 1996; (Anon, 200a)) Wild et al, 1994; (Johnson MR, Lambert DM & Hopkins S et al, 1996a). The tip of the gp41 protein does not effectively penetrate the host cell membrane, and the virus cannot infect the host cell with its RNA. The full exact mechanism of action is unclear, but may involve prevention of formation of an envelope glycoprotein structure required for fusion (Furuta et al, 1998).
    B) Enfuvirtide is active against HIV-1 in vitro (80-100 ng/mL for inhibition of infectivity, but this may vary depending on viral strain up to a factor of log(10)) (Tremblay et al, 2000; Derdeyn et al, 2000; p 115) Wild et al, 1994). A significant decrease in HIV-1 replication was observed in vivo (mouse model) with intraperitoneal doses of 200 mg/kg (p 221). It is unlikely that viral resistance would develop since enfuvirtide was produced from a segment of the HIV virus that is constant from one strain to another (James, 1998).
    C) Currently, this class of drugs is active only against HIV-1. However, due to the fusion inhibitor mechanism, other fusion inhibitors may be developed in the future for activity against other enveloped viruses, including influenza, hepatitis B, hepatitis C, and Ebola fever ((Anon, 2000b)).

Physicochemical

Physical Characteristics

    A) Enfuvirtide is a white to off-white amorphous solid with negligible solubility in water. The solubility increases in aqueous buffers (pH 7.5) to 85 to 142 g/100 mL (Prod Info FUZEON(R) subcutaneous injection, 2011).

Ph

    A) Enfuvirtide: approximately 9 (reconstituted solution) (Prod Info FUZEON(R) subcutaneous injection, 2011)

Molecular Weight

    A) Enfuvirtide: 4492 (Prod Info FUZEON(R) subcutaneous injection, 2011)

References

General Bibliography

    1) Anon : T20. Two part multicenter open label dose escalating study trials for children. Treatment experienced CD4+ range: not specified. Viral load: >10,000 copies/mL. . 2000c. Available from URL: http://www.viewtrialdetail.asp?trialID=592&HIVDrugID= 141%7Cpentafuside+%28T-20%29&.
    2) Anon: A controlled phase 2 trial assessing three doses of T-20 in combination with abacavir, amprenavir, and efavirenz in HIV-1 infected adults. AIDS CLinical Trials Information Service. Rockville, MD, USA. 2000. Available from URL: www.actis_10800.env?CQ_session_key=sojpgqkfltfy&cq_cur_document= 2&c.
    3) Anon: New drug reports from the HIV conference. Scrip 1999; 2409:21.
    4) Anon: T-20 ... from the AIDSDRUG library. AIDS Clinical Trials Information Service. Rockville, MD, USA. 2000b. Available from URL: www.actis_10800.env?cq_session_key=sojpgqkfltfy&cq_cur_document= 1&c.
    5) Anon: T-20(FDA295A). JAMA HIV Document. HealthGate. Burlington, MA, USA. 2000a. Available from URL: http://www.healthgate.com/choice/AMA/.../q-format.cgi?f=G&d=faidd&m= 306&ui=drg-030.
    6) Barney S, Guthrie K, & Davis D: Pentafuside (T20), a novel inhibitor of HIV-1 fusion and infection, is synergistic when used in combination with reverse transcriptase (RT) and protease inhibitors in vitro. Eleventh International Conference on Antiviral Research, A54 (abstract no. 48). Antiviral Res 1998; 37:3.
    7) Black PL, Wood O & Broud D et al: T-20, a novel inhibitor of HIV-1 fusion, blocks recovery of infectious HIV-1 and inhibits viral load in vivo in the HuPBMC-SC10 mouse model (abstract Tu.A.262). 11th International Conference on AIDS (July 9), 1996.
    8) Derdeyn CA, Decker JM, & Sfakianos JN: Sensitivity of human immunodeficiency virus type I to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J Virol 2000; 74:8358-8367.
    9) Furuta RA, Wild CT, & Weng Y: Capture of an early fusion-active conformation of HIV-1 gp41 (letter). Nat Struct Biol 1998; 5:276-279.
    10) Gilden D: T-20 and adefovir for salvage therapy - expect no miracles. GMHC Treat Issues 1998; 12:6-7.
    11) James JS: T-20 and Trimeris. AIDS Treat News 1998; 293:1-6.
    12) Johnson MR, Lambert DM & Hopkins S et al: Pentafuside (T-20): an amphipathic helical peptide-based membrane fusion inhibitor directed against HIV-1 gp41 (abstract 252). 211th American Chemical Society National Meeting (Mar 24), 1996a.
    13) Johnson MR, Lambert DM & Hopkins S et al: T-20: a peptide-based membrane fusion inhibitor directed against HIV-1 gp41 (abstract 335). 3rd Conference on Retroviruses and Opportunistic Infections (Jan 28), 1996.
    14) Julg B, Bogner JR, & Goebel FD: Severe hepatotoxicity associated with the combination of enfuvirtide and tipranavir/ritonavir: case report. AIDS 2006; 20(11):1563-.
    15) Lambert DM, Barney S, & Lambert AL: Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc Natl Acad Sci USA 1996; 93:2186-2191.
    16) Lawless MK, Hopkins S, & Anwer MK: Quantitation of a 36-amino-acid peptide inhibitor of HIV-1 membrane fusion in animal and human plasma using high-performance liquid chromatography and fluorescence detection. J Chromatogr B Biomed Sci Appl 1998; 707(1-2):213-217.
    17) M Saag : A short-term assessment of the safety, kinetics, and antiviral activity of t-29, an inhibitor of gp41 mediated membrane fusion. . 1997. Available from URL: http://207.78.88.28/IDSA97/abstract/a774.htm.
    18) Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission: Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. AIDSinfo, U.S. Department of Health and Human Services. Rockville, MD. 2012. Available from URL: http://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/0/. As accessed 2012-08-02.
    19) Product Information: FUZEON(R) subcutaneous injection, enfuvirtide subcutaneous injection. Roche Pharmaceuticals,Inc, Nutley, NJ, 2007.
    20) Product Information: FUZEON(R) subcutaneous injection, enfuvirtide subcutaneous injection. Genentech USA, Inc, South San Francisco, CA, 2011.
    21) Product Information: FUZEON(R) subcutaneous injection, enfuvirtide subcutaneous injection. Roche Laboratories Inc., Nutley, NJ, 2008.
    22) Tremblay CL, Kollman C, & Giguel F: Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100. J Acquir Immune Defic Syndr 2000; 25:99-102.
    23) Weizsaecker K, Kurowski M, Hoffmeister B, et al: Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide. Int J STD AIDS 2011; 22(5):294-295.