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The following adverse reactions are discussed in greater detail in other sections:

• Administration with Biojector® 2000 [see WARNINGS AND PRECAUTIONS]
• Pneumonia [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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 randomized, controlled, open-label, multicenter trials in treatment-experienced subjects, T20-301 (TORO 1) and T20-302 (TORO 2).

Local Injection Site Reactions

Local injection site reactions were the most frequent adverse events associated with the use of FUZEON. In 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 2). 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.

Table 2 : Summary of Individual Signs/Symptoms Characterizing Local Injection Site Reactions to Enfuvirtide in Studies T20-301 and T20-302 Combined (% of Subjects) Through 48 Weeks

Other Adverse Events

In T20-301 and T20-302, after study week 8, subjects 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 ISRs, 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 3. 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 3; events that occurred at a higher rate in the control arms are not displayed. Rates of adverse events for subjects who switched to FUZEON after virological failure were similar.

Table 3 : Rates of Treatment-Emergent Adverse Events* ( ≥ Grade 2) Reported in ≥ 2% of Subjects Treated with FUZEON** (Pooled Studies T20-301/T20-302 at 48 Weeks)

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 4 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 T20-301 and T20-302.

Table 4 : Treatment-Emergent Laboratory Abnormalities in ≥ 2% of Subjects Receiving FUZEON* (Pooled Studies T20-301 and T20-302 at 48 Weeks)

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.

See also CLINICAL PHARMACOLOGY

Potential for FUZEON to Affect Other Drugs

Based on the results from an in vitro human microsomal study, enfuvirtide is not an inhibitor of CYP450 enzymes. In an in vivo human metabolism study (N=12), FUZEON at the recommended dose of 90 mg twice daily did not alter the metabolism of CYP3A4, CYP2D6, CYP1A2, CYP2C19 or CYP2E1 substrates.

Potential for Other Drugs to Affect Enfuvirtide

Based on the available data, co-administration of FUZEON and other drugs which are inducers or inhibitors of CYP450 is not expected to alter the pharmacokinetics of enfuvirtide. No dose adjustments are needed when FUZEON is co-administered with other antiretroviral and non-antiretroviral drugs.

Last reviewed on RxList: 6/9/2011
This monograph has been modified to include the generic and brand name in many instances.