Rifapentine clinical studies
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Clinical Studies
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 data described below reflect exposure to Rifapentine in a randomized, open label, active-controlled trial of patients with pulmonary tuberculosis, excluding those with HIV-infection. The population consisted of primarily of male subjects with a mean age of 37 ± 11 years. In the initial 2 month phase of treatment (60 days), 361 patients received rifapentine 600 mg twice a week in combination with daily isoniazid, pyrazinamide, and ethambutol and 361 subjects received rifampin in combination with isoniazid, pyrazinamide and ethambutol all administered daily. Ethambutol was discontinued when drug susceptibly testing was completed. During the 4 month continuation phase, 321 patients in the rifapentine group continued to receive rifapentine 600 mg dosed once weekly with isoniazid and 307 patients in the rifampin arm received twice weekly rifampin and isoniazid. Both treatment groups received pyridoxine (Vitamin B6) over the 6 month treatment period.
Twenty-two deaths occurred in the study (eleven in the rifampin combination therapy group and eleven in the rifapentine combination therapy group).
In the study, 18/361 (5.0%) rifampin combination therapy patients discontinued the study due to an adverse reaction compared to 11/361 (3.0%) rifapentine combination therapy patients. Three patients (two rifampin combination therapy patients and one rifapentine combination therapy patient) were discontinued in the Initial Phase as a result of hepatitis with increased liver function tests (ALT, AST, LDH, and bilirubin). Concomitant medications for all three patients included isoniazid, pyrazinamide, ethambutol, and pyridoxine. The two rifampin patients and one rifapentine patient recovered without sequelae.
As shown in Table 1, hyperuricemia was the most frequently reported reaction and was most likely related to the pyrazinamide since only two cases were reported in the Continuation Phase when this drug was no longer included in the treatment regimen.
Seven patients had adverse reactions associated with an overdose. In the rifampin combination group these reactions included hematuria, anorexia, back pain, arthralgia, and myalgia. In the rifapentine combination group these reactions included hematuria, neutropenia, hyperglycemia, ALT increased, hyperuricemia, pruritus, and arthritis.
The following table (Table 1) presents treatment-emergent adverse reactions associated with the use of any of the four drugs in the regimens (rifapentine/rifampin, isoniazid, pyrazinamide, or ethambutol) which occurred in ≥1% of patients during treatment and post-treatment through the first three months of follow-up.[1]
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References
Adapted from the FDA Package Insert.