t;20 18/19 (95%) 18.1/19 (95%)
20 to <25 18/18 (100%) 17.8/18 (99%)
25+ 6/6 (100%) 6/6 (100%)
* Successful treatment was defined as improvement in clinical and respiratory measures persisting at least 4 weeks after cessation of therapy. This was based on data from patients for which both outcome and steady-state plasma atovaquone concentration data are available.
† Based on logistic regression analysis.
A dosing regimen of MEPRON Suspension for the treatment of mild-to-moderate PCP has been selected to achieve average plasma atovaquone concentrations of approximately 20 mcg/mL, because this plasma concentration was previously shown to be well tolerated and associated with the highest treatment success rates (Table 2). In an open-label PCP treatment study with MEPRON Suspension, dosing regimens of 1,000 mg once daily, 750 mg twice daily, 1,500 mg once daily, and 1,000 mg twice daily were explored. The average steady-state plasma atovaquone concentration achieved at the 750-mg twice-daily dose given with meals was 22.0 ± 10.1 mcg/mL (n = 18).
INDICATIONS AND USAGE
MEPRON Suspension is indicated for the prevention of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX).
MEPRON Suspension is also indicated for the acute oral treatment of mild-to-moderate PCP in patients who are intolerant to TMP-SMX.
Prevention of PCP
The indication for prevention of PCP is based on the results of 2 clinical trials comparing MEPRON Suspension to dapsone or aerosolized pentamidine in HIV-infected adult and adolescent patients at risk of PCP (CD4 count <200 cells/mm3 or a prior episode of PCP) and intolerant to TMP-SMX.
Dapsone Comparative Study
This randomized, open-label trial enrolled a total of 1,057 patients at 48 study centers. Patients were randomized to receive 1,500 mg MEPRON Suspension once daily (n = 536) or 100 mg dapsone once daily (n = 521). Median follow-up was 24 months. Patients randomized to the dapsone arm who were seropositive for Toxoplasma gondii and had a CD4 count <100 cells/mm3 also received pyrimethamine and folinic acid. PCP event rates are shown in Table 3. There was no significant difference in mortality rates between the groups.
Aerosolized Pentamidine Comparative Study
This randomized, open-label trial enrolled a total of 549 patients at 35 study centers. Patients were randomized to receive 1,500 mg MEPRON Suspension once daily (n = 175), 750 mg MEPRON Suspension once daily (n = 188), or 300 mg aerosolized pentamidine once monthly (n = 186). Median follow-up was 11.3 months. The results of the PCP event rates appear in Table 3. There were no significant differences in mortality rates among the groups.
Table 3. Confirmed or Presumed/Probable PCP Events(As-Treated Analysis) *
Assessment Study 115-211 Study 115-213
Atovaquone
1,500 mg/day
(n = 527)
Dapsone
100 mg/day
(n = 510)
Atovaquone
750 mg/day
(n = 188)
Atovaquone
1,500 mg/day
(n = 172)
Aerosolized
Pentamidine
300 mg/month
(n = 169)
% 15% 19% 23% 18% 17%
Relative Risk†
(CI)‡
0.77
(0.57, 1.04)
1.47
(0.86, 2.50)
1.14
(0.63, 2.06)
* Those events occurring during or within 30 days |
