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FUZEON®
(enfuvirtide)
for Injection
DESCRIPTION
FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4+ cells. Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues.
Enfuvirtide is a white to off-white amorphous solid. It has negligible solubility in pure water and the solubility increases in aqueous buffers (pH 7.5) to 85-142 g/100 mL. The empirical formula of enfuvirtide is C204H301N51O64, and the molecular weight is 4492. It has the following primary amino acid sequence:
CH3CO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NH2 and the following structural formula:
The drug product, FUZEON (enfuvirtide) for Injection, is a white to off-white, sterile, lyophilized powder. Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the spans of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provide the delivery of 1 mL of the solution. Each 1 mL of the reconstituted solution contains approximately 90 mg of enfuvirtide with approximate amounts of the following excipients: 22.55 mg of mannitol, 2.39 mg of sodium carbonate (anhydrous), and sodium hydroxide and hydrochloric acid for pH adjustment as needed. The reconstituted solution has an approximate pH of 9.0.
MICROBIOLOGY
Mechanism of Action
Enfuvirtide interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes.
Antiviral Activity In Vitro
The in vitro antiviral activity of enfuvirtide was assessed by infecting different CD4+ cell types with laboratory and clinical isolates of HIV-1. The IC50 values for baseline clinical isolates ranged from 0.089 to 107 nM (0.4 to 480 ng/mL) by the cMAGI assay (n=130) and from 1.56 to 1680 nM (7 to 7530 ng/mL) by a recombinant phenotypic entry assay (n=627). Enfuvirtide was similarly active in vitro against clades A, AE, C, D, E, F, and G (range 5.1 to 10.5 nM), and R5, X4, and dual tropic viruses. Enfuvirtide has no activity against HIV-2.
Enfuvirtide exhibited additive to synergistic effects in cell culture assays when combined with individual members of various antiretroviral classes, including lamivudine, zidovudine, indinavir, nelfinavir, and efavirenz.
Drug Resistance
HIV-1 isolates with reduced susceptibility to enfuvirtide have been selected in vitro. Genotypic analysis of the in vitro-selected resistant isolates showed mutations that resulted in amino acid substitutions at the enfuvirtide binding HR1 domain positions 36 to 38 of the HIV-1 envelope glycoprotein gp41. Phenotypic analysis of site-directed mutants in positions 36 to 38 in an HIV-1 molecular clone showed a 5-fold to 684-fold decrease in susceptibility to enfuvirtide.
In clinical trials, HIV-1 isolates with reduced susceptibility to enfuvirtide have been recovered from subjects failing a FUZEON containing regimen. Posttreatment HIV-1 virus from 277 subjects experiencing protocol defined virological failure at 48 weeks exhibited a median decrease in susceptibility to enfuvirtide of 33.4-fold (range 0.4-6318-fold) relative to their respective baseline virus. Of these, 249 had decreases in susceptibility to enfuvirtide of greater than 4-fold and all but 3 of those 249 exhibited genotypic changes in the codons encoding gp41 HR1 domain amino acids 36 to 45. Substitutions in this region were observed with decreasing frequency at amino acid positions 38, 43, 36, 40, 42, and 45.
Cross-resistance
HIV-1 clinical isolates resistant to nucleoside analogue reverse transcriptase inhibitors (NRTI), non-nucleoside analogue reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI) were susceptible to enfuvirtide in cell culture.
CLINICAL PHARMACOLOGY
Pharmacokinetics
The pharmacokinetic properties of enfuvirtide were evaluated in HIV-1 infected adult and pediatric patients.
Special Populations
Drug Interactions
INDICATIONS AND USAGE
FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
This indication is based on results from two controlled studies of 48 weeks duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of FUZEON in antiretroviral naive patients.
Description of Clinical Studies
CONTRAINDICATIONS
FUZEON is contraindicated in patients with known hypersensitivity to FUZEON or any of its components (see WARNINGS).
WARNINGS
Local Injection Site Reactions (ISRs)
The majority of patients (98%) receiving FUZEON in the Phase 3 clinical trials had at least one local injection site reaction; ISRs occurred throughout treatment with FUZEON. Manifestations may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis (see ADVERSE REACTIONS). Reactions are often present at more than one injection site. Patients must be familiar with the FUZEON Injection Instructions in order to know how to inject FUZEON appropriately and how to monitor carefully for signs or symptoms of cellulitis or local infection.
Pneumonia
An increased rate of bacterial pneumonia was observed in subjects treated with FUZEON in the Phase 3 clinical trials compared to the control arm (see ADVERSE REACTIONS). It is unclear if the increased incidence of pneumonia is related to FUZEON use. However, because of this finding, patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia, especially if they have underlying conditions which may predispose them to pneumonia. Risk factors for pneumonia included low initial CD4+ cell count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease (see ADVERSE REACTIONS).
Hypersensitivity Reactions
Systemic hypersensitivity reactions have been associated with FUZEON therapy and may recur on re-challenge. Hypersensitivity reactions have occurred in <1% of patients studied and have included combinations of: rash, fever, nausea and vomiting, chills, rigors, hypotension, and/or elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving FUZEON include primary immune complex reaction, respiratory distress, glomerulonephritis, and Guillain-Barre syndrome. Patients developing signs and symptoms suggestive of a systemic hypersensitivity reaction should discontinue FUZEON and should seek medical evaluation immediately. Therapy with FUZEON should not be restarted following systemic signs and symptoms consistent with a hypersensitivity reaction. Risk factors that may predict the occurrence or severity of hypersensitivity to FUZEON have not been identified (see ADVERSE REACTIONS).
PRECAUTIONS
Non-HIV Infected Individuals
There is a theoretical risk that FUZEON use may lead to the production of anti-enfuvirtide antibodies which cross react with HIV gp41. This could result in a false positive HIV test with an ELISA assay; a confirmatory western blot test would be expected to be negative. FUZEON has not been studied in non-HIV infected individuals.
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including FUZEON. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP] or tuberculosis), which may necessitate further evaluation and treatment.
Administration with Biojector® 2000
Nerve pain (neuralgia and/or paresthesia) lasting up to 6 months associated with administration at anatomical sites where large nerves course close to the skin, bruising and hematomas (see ADVERSE REACTIONS) have occurred with use of the Biojector 2000 needle-free device for administration of FUZEON. Patients receiving anticoagulants or persons with hemophilia, or other coagulation disorders, may have a higher risk of post-injection bleeding.
Information for Patients
To assure safe and effective use of FUZEON, the following information and instructions should be given to patients:
- Patients should be informed that injection site reactions occur in almost all patients taking FUZEON. Patients must be familiar with the FUZEON Injection Instructions for instructions on how to appropriately inject FUZEON and how to carefully monitor for signs or symptoms of cellulitis or local infection. Patients should be instructed when to contact their healthcare provider about these reactions.
- Patients should be made aware that an increased rate of bacterial pneumonia was observed in subjects treated with FUZEON in Phase 3 clinical trials compared to the control arm. Patients should be advised to seek medical evaluation immediately if they develop signs or symptoms suggestive of pneumonia (cough with fever, rapid breathing, shortness of breath) (see WARNINGS).
- Patients should be advised of the possibility of a systemic hypersensitivity reaction to FUZEON. Patients should be advised to discontinue therapy and immediately seek medical evaluation if they develop signs/symptoms of systemic hypersensitivity such as combinations of rash, fever, nausea and vomiting, chills, rigors, and/or hypotension (see WARNINGS).
- FUZEON is not a cure for HIV-1 infection and patients may continue to contract illnesses associated with HIV-1 infection. The long-term effects of FUZEON are unknown at this time. FUZEON therapy has not been shown to reduce the risk of transmitting HIV-1 to others through sexual contact or blood contamination.
- FUZEON must be taken as part of a combination antiretroviral regimen. Use of FUZEON alone may lead to rapid development of virus resistant to FUZEON and possibly other agents of the same class.
- Patients and caregivers must be instructed in the use of aseptic technique when administering FUZEON in order to avoid injection site infections. Appropriate training for FUZEON reconstitution and self-injection must be given by a healthcare provider, including a careful review of the FUZEON Patient Package Insert and FUZEON Injection Instructions. The first injection should be performed under the supervision of an appropriately qualified healthcare provider. It is recommended that the patient and/or caregiver's understanding and use of aseptic injection techniques and procedures be periodically re-evaluated.
- Patients and caregivers should be instructed on the preferred anatomical sites for administration (upper arm, abdomen, anterior thigh). FUZEON should not be injected near any anatomical areas where large nerves course close to the skin, such as near the elbow, knee, groin or the inferior or medial sections of the buttocks, skin abnormalities, including directly over a blood vessel, into moles, scar tissue, bruises, or near the navel, surgical scars, tattoos or burn sites.
- Patients and caregivers should be instructed in the proper techniques for preparation, injection and disposal of needles and syringes (including not recapping needles) in order to avoid needle stick injuries. Patients should be told not to reuse needles or syringes, and be instructed in safe disposal procedures including the use of a puncture-resistant container for disposal of used needles and syringes. Patients must be instructed on the safe disposal of full containers as per local requirements. Caregivers who experience an accidental needle stick after patient injection should contact a healthcare provider immediately.
- Patients should contact their healthcare provider for any questions regarding the administration of FUZEON.
- Patients should inform their healthcare provider if they are pregnant, plan to become pregnant or become pregnant while taking this medication.
- Patients should inform their healthcare provider if they are breast-feeding.
- Patients should not change the dose or dosing schedule of FUZEON or any antiretroviral medication without consulting their healthcare provider.
- Patients should contact their healthcare provider immediately if they stop taking FUZEON or any other drug in their antiretroviral regimen.
- Patients should be told that they can obtain more information on the self-administration of FUZEON at www.FUZEON.com or by calling 1-877-4-FUZEON (1-877-438-9366).
Patients should be advised that no studies have been conducted on the ability to drive or operate machinery while taking FUZEON. If patients experience dizziness while taking FUZEON, they should be advised to talk to their healthcare provider before driving or operating machinery.
Drug Interactions
Carcinogenesis, Mutagenesis, Impairment of Fertility
Pregnancy
Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 27 times and 3.2 times the adult human dose on a m2 basis. The animal studies revealed no evidence of harm to the fetus from enfuvirtide. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Antiretroviral Pregnancy Registry
To monitor maternal-fetal outcomes of pregnant women exposed to FUZEON and other antiretroviral drugs, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
Nursing Mothers
The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. It is not known whether enfuvirtide is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving FUZEON.
Studies where radio-labeled 3H-enfuvirtide was administered to lactating rats indicated that radioactivity was present in the milk. It is not known whether the radioactivity in the milk was from radio-labeled enfuvirtide or from radio-labeled metabolites of enfuvirtide (ie, amino acids and peptide fragments).
Pediatric Use
The safety and pharmacokinetics of FUZEON have not been established in pediatric subjects below 6 years of age; limited efficacy data is available in pediatric subjects 6 years of age and older.
Sixty-three HIV-1 infected pediatric subjects ages 5 through 16 years have received FUZEON in two open-label, single-arm clinical trials. Adverse experiences, including ISRs, were similar to those observed in adult patients.
Study T20-204 was an open-label, multicenter trial that evaluated the safety and antiviral activity of FUZEON in treatment-experienced pediatric subjects. Eleven subjects from 6 to 12 years were enrolled (median age of 9 years). Median baseline CD4+ cell count was 495 cells/µL and the median baseline HIV-1 RNA was 4.6 log10 copies/mL.
Ten of the 11 study subjects completed 48 weeks of chronic therapy. At week 48, 6/11 (55%) subjects had ≥1 log10 decline in HIV-1 RNA and 4/11 (36%) subjects were below 400 copies/mL of HIV-1 RNA. The median changes from baseline (for the As Treated population) in HIV-1 RNA and CD4+ cell count were -1.48 log10 copies/mL and +122 cells/µL, respectively.
Study T20-310 was an open-label, multicenter trial that evaluated the pharmacokinetics, safety, and antiviral activity of FUZEON in treatment-experienced pediatric subjects and adolescents. Fifty-two subjects from 5 through 16 years were enrolled (median age of 12 years). Median baseline CD4+ cell count was 117 cells/µL and the median baseline HIV-1 RNA was 5.0 log10 copies/mL.
Thirty-two of the 52 study subjects completed 48 weeks of chronic therapy. At week 48, 17/52 (33%) of subjects had ≥1 log10 decline in HIV-1 RNA, 11/52 (21%) of subjects were below 400 copies/mL of HIV-1 RNA and 5/52 (10%) were below 50 copies/mL. The median changes from baseline (for the As Treated population) in HIV-1 RNA and CD4+ cell count were -1.17 log10 copies/mL and +106 cells/µL, respectively.
Geriatric Use
Clinical studies of FUZEON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
ADVERSE REACTIONS
The overall safety profile of FUZEON is based on 2131 subjects who received at least 1 dose of FUZEON during various clinical trials. This includes 2051 adults, 658 of whom received the recommended dose for greater than 48 weeks, and 63 pediatric subjects.
Assessment of treatment-emergent adverse events is based on the pooled data from the two Phase 3 studies T20-301 and T20-302.
Local Injection Site Reactions
Local injection site reactions were the most frequent adverse events associated with the use of FUZEON. In Phase 3 clinical studies (T20-301 and T20-302), 98% of subjects had at least one local injection site reaction (ISR). A total of 7% of subjects discontinued treatment with FUZEON because of ISRs (4%) or difficulties with injecting FUZEON (3%) such as injection fatigue and inconvenience. Eighty-five percent of subjects experienced their first ISR during the initial week of treatment; ISRs continued to occur throughout treatment with FUZEON. For most subjects the severity of signs and symptoms associated with ISRs did not change during the 48 weeks of treatment. The majority of ISRs were associated with erythema, induration, the presence of nodules or cysts, and mild to moderate pain at the injection site (Table 4). In addition, the average duration of individual ISRs was between three and seven days in 41% of subjects and more than seven days in 24% of subjects. Also, the numbers of ISRs per subject at any one time was between six to 14 ISRs in 26% of subjects and more than 14 ISRs in 1.3% of subjects. Infection at the injection site (including abscess and cellulitis) was reported in 1.7% of adult subjects.
| N=663 | |||
|---|---|---|---|
| Event Category | Any Severity Grade | % of Patients with Grade 3 Reactions | % of Patients with Grade 4 Reactions |
| Pain/Discomfort Grade 4 = severe pain requiring hospitalization or prolongation of hospitalization, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant. | 96% | 11% | 0% |
| Induration | 90% | 39% | 18% |
| >25 but <50 mm | ≥50 mm | ||
| Erythema | 91% | 22% | 10% |
| >50 but <85 mm | ≥85 mm | ||
| Nodules and Cysts | 80% | 23% | 0.2% |
| >3 cm average diameter | draining | ||
| Pruritus | 65% | 3% | NA |
| Ecchymosis | 52% | 5% | 2% |
| >3 but ≤5 cm | >5 cm | ||
Other Adverse Events
Systemic hypersensitivity reactions have been attributed to FUZEON (≤1%) and in some cases have recurred upon re-challenge (see WARNINGS).
In the T20-301 and T20-302 studies, after study week 8, patients on background alone who met protocol defined criteria for virological failure were permitted to revise their background regimens and add FUZEON. Exposure on FUZEON+background was 557 patient-years, and to background alone 162 patient-years. Due to this difference in exposure, safety results are expressed as the number of patients with an adverse event per 100 patient-years of exposure. For FUZEON+background, adverse events are also displayed by percent of subjects.
The events most frequently reported in subjects receiving FUZEON+background regimen, excluding injection site reactions, were diarrhea (38 per 100 patient-years or 31.7%), nausea (27 per 100 patient-years or 22.8%), and fatigue (24 per 100 patient-years or 20.2%). These events were also commonly observed in subjects that received background regimen alone: diarrhea (73 per 100 patient-years), nausea (50 per 100 patient-years), and fatigue (38 per 100 patient-years).
Treatment-emergent adverse events, regardless of causality and excluding ISRs, from Phase 3 studies are summarized for adult subjects, in Table 5. Any Grade 2 or above events occurring at ≥2 percent of subjects and at a higher rate in subjects treated with FUZEON are summarized in Table 5; events that occurred at a higher rate in the control arms are not displayed.
Rates of adverse events for patients who switched to FUZEON after virological failure were similar.
| Adverse Event (by System Organ Class) | FUZEON+Background Regimen (N=663) | FUZEON+Background Regimen (N=663) | Background Regimen (N=334) |
|---|---|---|---|
| 663 patients total | 557 total patient-years | 162 total patient-years | |
| % frequency | rate/100 patient-years | rate/100 patient-years | |
| Weight Decreased | 6.6% | 7.9 | 6.2 |
| Sinusitis | 6.0% | 7.2 | 4.9 |
| Abdominal Pain | 3.9% | 4.7 | 3.7 |
| Cough | 3.9% | 4.7 | 2.5 |
| Herpes Simplex | 3.5% | 4.1 | 3.7 |
| Appetite Decreased | 3.2% | 3.8 | 2.5 |
| Pancreatitis | 3.0% | 3.6 | 2.5 |
| Pain in Limb | 2.9% | 3.4 | 3.1 |
| Pneumonia (see div below) | 2.7% | 3.2 | 0.6 |
| Myalgia | 2.7% | 3.2 | 1.2 |
| Influenza-Like Illness | 2.4% | 2.9 | 1.9 |
| Folliculitis | 2.4% | 2.9 | 2.5 |
| Anorexia | 2.3% | 2.7 | 1.9 |
| Dry Mouth | 2.1% | 2.5 | 1.9 |
| Conjunctivitis | 2.0% | 2.3 | 1.9 |
The incidence of pneumonia was 2.7% or 3.2 events/100 patient-years in subjects receiving FUZEON+background regimen. On analysis of all diagnoses of pneumonia (pneumonia, bacterial pneumonia, bronchopneumonia, and related terms) in the Phase 3 clinical trials, an increased rate of bacterial pneumonia was observed in subjects treated with FUZEON compared to the control arm (6.9%, 6.7 pneumonia events per 100 patient-years versus 0.6 events per 100 patient-years, respectively). Approximately half of the study subjects with pneumonia required hospitalization. Three subject deaths in the FUZEON arm were attributed to pneumonia; all three had serious concomitant AIDS-related illnesses that contributed to their deaths. Risk factors for pneumonia included low initial CD4+ lymphocyte count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease. It is unclear if the increased incidence of pneumonia was related to FUZEON use. However, because of this, finding patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia, especially if they have underlying conditions which may predispose them to pneumonia (see WARNINGS).
Less Common Events
The following adverse events have been reported in 1 or more subjects; however, a causal relationship to FUZEON has not been established.
Immune System Disorders: worsening abacavir hypersensitivity reaction
Renal and Urinary Disorders: glomerulonephritis; tubular necrosis; renal insufficiency; renal failure (including fatal cases)
Blood and Lymphatic Disorders: thrombocytopenia; neutropenia; fever; lymphadenopathy
Endocrine and Metabolic: hyperglycemia
Infections: sepsis; herpes simplex
Nervous System Disorders: taste disturbance; Guillain-Barre syndrome (fatal); sixth nerve palsy; peripheral neuropathy
Cardiac Disorders: unstable angina pectoris
Gastrointestinal Disorders: constipation; abdominal pain upper
General: asthenia
Hepatobiliary Disorders: toxic hepatitis; hepatic steatosis
Investigations: increased amylase; increased lipase; increased AST; increased GGT; increased triglycerides
Psychiatric Disorders: insomnia; depression; anxiety; suicide attempt
Respiratory, Thoracic, and Mediastinal Disorders: pneumopathy; respiratory distress; cough
Skin and Subcutaneous Tissue Disorders: pruritus
Laboratory Abnormalities
Table 6 shows the treatment-emergent laboratory abnormalities that occurred in at least 2 subjects per 100 patient-years and more frequently in those receiving FUZEON+background regimen than background regimen alone from studies T20-301 and T20-302.
| Laboratory Parameters | Grading | FUZEON+Background Regimen (N=663) | FUZEON+Background Regimen (N=663) | Background Regimen (N=334) |
|---|---|---|---|---|
| 663 patients total | 557 total patient-years | 162 total patient-years | ||
| % frequency | rate/100 patient-years | rate/100 patient-years | ||
| Eosinophilia | ||||
| 1-2 × ULN (0.7× 109/L) | 0.7-1.4 × 109/L | 9.1% | 10.8 | 3.7 |
| >2 × ULN (0.7× 109/L) | >1.4 × 109/L | 1.8% | 2.2 | 1.8 |
| ALT | ||||
| Grade 3 | >5-10 × ULN | 4.1% | 4.8 | 4.3 |
| Grade 4 | >10 × ULN | 1.2% | 1.4 | 1.2 |
| Creatine Phosphokinase (U/L) | ||||
| Grade 3 | >5-10 × ULN | 6.9% | 8.3 | 8.0 |
| Grade 4 | >10 × ULN | 2.6% | 3.1 | 8.6 |
Adverse Events in Pediatric Patients
FUZEON has been studied in 63 pediatric subjects 5 through 16 years of age with duration of FUZEON exposure ranging from 1 dose to 134 weeks. Adverse experiences seen during clinical trials were similar to those observed in adult subjects, although infections at site of injection (cellulitis or abscess) were more frequent in adolescents than in adults, with 4 events occurring in 3 of 28 (11%) subjects.
OVERDOSAGE
There are no reports of human experience of acute overdose with FUZEON. The highest dose administered to 12 subjects in a clinical trial was 180 mg as a single dose subcutaneously. There is no specific antidote for overdose with FUZEON. Treatment of overdose should consist of general supportive measures.
DOSAGE AND ADMINISTRATION
Adults
The recommended dose of FUZEON is 90 mg (1 mL) twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site, and only where there is no current injection site reaction from an earlier dose. FUZEON should not be injected near any anatomical areas where large nerves course close to the skin, such as near the elbow, knee, groin or the inferior or medial section of the buttocks, skin abnormalities, including directly over a blood vessel, into moles, scar tissue, bruises, or near the navel, surgical scars, tattoos or burn sites. Additional detailed information regarding the administration of FUZEON is described in the FUZEON Injection Instructions.
Pediatric Patients
Insufficient data are available to establish a dose recommendation of FUZEON in pediatric patients below the age of 6 years. In pediatric patients 6 years through 16 years of age, the recommended dosage of FUZEON is 2 mg/kg twice daily up to a maximum dose of 90 mg twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site and only where there is no current injection site reaction from an earlier dose. FUZEON should not be injected into moles, scar tissue, bruises or the navel. Table 7 contains dosing guidelines for FUZEON based on body weight. Weight should be monitored periodically and the FUZEON dose adjusted accordingly.
| Weight | Dose per bid Injection (mg/dose) | Injection Volume (90 mg enfuvirtide per mL) | |
|---|---|---|---|
| Kilograms (kg) | Pounds (lbs) | ||
| 11.0 to 15.5 | 24 to 34 | 27 | 0.3 mL |
| 15.6 to 20.0 | >34 to 44 | 36 | 0.4 mL |
| 20.1 to 24.5 | >44 to 54 | 45 | 0.5 mL |
| 24.6 to 29.0 | >54 to 64 | 54 | 0.6 mL |
| 29.1 to 33.5 | >64 to 74 | 63 | 0.7 mL |
| 33.6 to 38.0 | >74 to 84 | 72 | 0.8 mL |
| 38.1 to 42.5 | >84 to 94 | 81 | 0.9 mL |
| ≥42.6 | >94 | 90 | 1.0 mL |
Directions for Use
For more detailed instructions, see FUZEON Injection Instructions.
HOW SUPPLIED
FUZEON (enfuvirtide) for Injection is a white to off-white, sterile, lyophilized powder and it is packaged in a single-use clear glass vial containing 108 mg of enfuvirtide for the delivery of approximately 90 mg/1 mL when reconstituted with 1.1 mL of Sterile Water for Injection.
FUZEON is available in a Convenience Kit containing 60 single-use vials of FUZEON (90 mg strength), 60 vials (2 cartons of 30 each) of Sterile Water for Injection (1.1 mL per vial), 60 reconstitution syringes (3 cc), 60 administration syringes (1 cc), alcohol wipes, Package Insert, Patient Package Insert, and Injection Instruction Guide (NDC 0004-0380-39).
Storage Conditions
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Reconstituted solution should be stored under refrigeration at 2° to 8°C (36° to 46°F) and used within 24 hours.
Roche and FUZEON are trademarks of Hoffmann-La Roche Inc.
Biojector is a trademark of Bioject Medical Technologies, Inc.
FUZEON has been jointly developed by Trimeris, Inc. and Hoffmann-La Roche Inc. FUZEON is manufactured by Hoffmann-La Roche Inc.
| Distributed by: Roche Pharmaceuticals Roche Laboratories Inc. 340 Kingsland Street Nutley, New Jersey 07110-1199 www.rocheusa.com | Licensed from: Trimeris, Inc. 3500 Paramount Parkway Morrisville, North Carolina 27560 www.trimeris.com | |
27899354
Rev: January 2007
Copyright © 2003-2007 by Roche Laboratories Inc. and Trimeris, Inc. All rights reserved.