Maraviroc adverse reactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Adverse Reactions
The following adverse reactions are discussed in other sections of the labeling:
Hepatotoxicity Cardiovascular events
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.
Studies in Treatment-Experienced Subjects
The safety profile of SELZENTRY is primarily based on 840 HIV-infected subjects who received at least one dose of SELZENTRY during two Phase 3 trials. A total of 426 of these subjects received the indicated twice daily dosing regimen.
Assessment of treatment-emergent adverse events is based on the pooled data from two studies in subjects with CCR5-tropic HIV-1 (A4001027 and A4001028). The median duration of maraviroc therapy for subjects in these studies was 48 weeks, with the total exposure on SELZENTRY twice daily at 309 patient-years versus 111 patient-years on placebo + OBT. The population was 89% male and 84% white, with mean age of 46 years (range 17–75 years). Subjects received dose equivalents of 300 mg maraviroc once or twice daily.
The most common adverse events reported with SELZENTRY twice daily therapy with frequency rates higher than placebo, regardless of causality, were upper respiratory tract infections, cough, pyrexia, rash, and dizziness. Additional adverse events that occurred with once daily dosing at a higher rate than both placebo and twice daily dosing were diarrhea, edema, influenza, esophageal candidiasis, sleep disorders, rhinitis, parasomnias, and urinary abnormalities. In these two studies, the rate of discontinuation due to adverse events was 5% for subjects who received SELZENTRY twice daily + optimized background therapy (OBT) as well as those who received placebo + OBT. Most of the adverse events reported were judged to be mild to moderate in severity. The data described below occurred with SELZENTRY twice daily dosing.
The total number of subjects reporting infections were 233 (55%) and 84 (40%) in the SELZENTRY twice daily and placebo groups, respectively. Correcting for the longer duration of exposure on SELZENTRY compared to placebo, the exposure-adjusted frequency (rate per 100 subject-years) of these events was 133 for both SELZENTRY twice daily and placebo.
Dizziness or postural dizziness occurred in 8% of subjects on either SELZENTRY or placebo, with 2 subjects (0.5%) on SELZENTRY permanently discontinuing therapy (1 due to syncope, 1 due to orthostatic hypotension) versus 1 subject on placebo (0.5%) permanently discontinuing therapy due to dizziness.
Treatment-emergent adverse events, regardless of causality, from A4001027 and A4001028 are summarized in Table 3. Selected events occurring at ≥2% of subjects and at a numerically higher rate in subjects treated with SELZENTRY are included; events that occurred at the same or higher rate on placebo are not displayed.[1]
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Laboratory Abnormalities
Table 4 shows the treatment-emergent Grade 3–4 laboratory abnormalities that occurred in >2% of subjects receiving SELZENTRY.
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Study in Treatment-Naïve Subjects
Treatment-Emergent Adverse Events
Treatment-emergent adverse events, regardless of causality, from Study A4001026, a double-blind comparative controlled study in which 721 treatment-naïve subjects received SELZENTRY 300 mg BID (N=360) or efavirenz (N=361) in combination with zidovudine/lamivudine for 96 weeks, are summarized in Table 5. Selected events occurring at ≥ 2% of subjects and at a numerically higher rate in subjects treated with SELZENTRY are included; events that occurred at the same or higher rate on efavirenz are not displayed.
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Less Common Adverse Events in Clinical Trials
The following adverse events occurred in <2% of SELZENTRY-treated subjects. These events have been included because of their seriousness and either increased frequency on SELZENTRY or are potential risks due to the mechanism of action. Events attributed to the patient's underlying HIV infection are not listed.
Blood and Lymphatic System: marrow depression and hypoplastic anemia
Cardiac Disorders: unstable angina, acute cardiac failure, coronary artery disease, coronary artery occlusion, myocardial infarction, myocardial ischemia
Hepatobiliary Disorders: hepatic cirrhosis, hepatic failure, cholestatic jaundice, portal vein thrombosis, hypertransaminasemia, jaundice
Infections and Infestations: endocarditis, infective myositis, viral meningitis, pneumonia, treponema infections, septic shock, Clostridium difficile colitis, meningitis
Musculoskeletal and Connective Tissue Disorders: myositis, osteonecrosis, rhabdomyolysis, blood CK increased
Neoplasms benign, Malignant and Unspecified (including Cysts and Polyps): abdominal neoplasm, anal cancer, basal cell carcinoma, Bowen's disease, cholangiocarcinoma, diffuse large B-cell lymphoma, lymphoma, metastases to liver, esophageal carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma, squamous cell carcinoma of skin, tongue neoplasm (malignant stage unspecified), anaplastic large cell lymphomas T- and null-cell types, bile duct neoplasms malignant, endocrine neoplasms malignant and unspecified
Nervous System Disorders: cerebrovascular accident, convulsions and epilepsy, tremor (excluding congenital), facial palsy, hemianopia, loss of consciousness, visual field defect
References
Adapted from the FDA Package Insert.