8 ± 3.2
(n = 4)
15.4 ± 6.6
(n = 4)
>2-13 years
16.8 ± 6.4
(n = 4)
37.1 ± 10.9
(n = 3)
______
Hepatic/Renal Impairment
The pharmacokinetics of atovaquone have not been studied in patients with hepatic or renal impairment.
Drug Interactions
Rifampin
In a study with 13 HIV-infected volunteers, the oral administration of rifampin 600 mg every 24 hours with MEPRON Suspension 750 mg every 12 hours resulted in a 52% ± 13% decrease in the average steady-state plasma atovaquone concentration and a 37% ± 42% increase in the average steady-state plasma rifampin concentration. The half-life of atovaquone decreased from 82 ± 36 hours when administered without rifampin to 50 ± 16 hours with rifampin.
Rifabutin, another rifamycin, is structurally similar to rifampin and may possibly have some of the same drug interactions as rifampin. No interaction trials have been conducted with MEPRON and rifabutin.
Trimethoprim/Sulfamethoxazole (TMP-SMX)
The possible interaction between atovaquone and TMP-SMX was eva luated in 6 HIV-infected adult volunteers as part of a larger multiple-dose, dose-escalation, and chronic dosing study of MEPRON Suspension. In this crossover study, MEPRON Suspension 500 mg once daily, or TMP-SMX tablets (160 mg trimethoprim and 800 mg sulfamethoxazole) twice daily, or the combination were administered with food to achieve steady state. No difference was observed in the average steady-state plasma atovaquone concentration after coadministration with TMP-SMX. Coadministration of MEPRON with TMP-SMX resulted in a 17% and 8% decrease in average steady-state concentrations of trimethoprim and sulfamethoxazole in plasma, respectively. This effect is minor and would not be expected to produce clinically significant events.
Zidovudine
Data from 14 HIV-infected volunteers who were given atovaquone tablets 750 mg every 12 hours with zidovudine 200 mg every 8 hours showed a 24% ± 12% decrease in zidovudine apparent oral clearance, leading to a 35% ± 23% increase in plasma zidovudine AUC. The glucuronide metabolite:parent ratio decreased from a mean of 4.5 when zidovudine was administered alone to 3.1 when zidovudine was administered with atovaquone tablets. This effect is minor and would not be expected to produce clinically significant events. Zidovudine had no effect on atovaquone pharmacokinetics.
Relationship Between Plasma Atovaquone Concentration and Clinical Outcome
In a comparative study of atovaquone tablets with TMP-SMX for oral treatment of mild-to-moderate Pneumocystis carinii pneumonia (PCP) (see INDICATIONS AND USAGE), where AIDS patients received 750 mg atovaquone tablets 3 times daily for 21 days, the mean steady-state atovaquone concentration was 13.9 ± 6.9 mcg/mL (n = 133). Analysis of these data established a relationship between plasma atovaquone concentration and successful treatment. This is shown in Table 2.
Table 2. Relationship Between Plasma Atovaquone Concentration and Successful Treatment
Steady-State Plasma
Atovaquone Concentrations
Successful Treatment*
(No. Successes/No. in Group) (%)
(mcg/mL) Observed Predicted†
0 to <5 0/6 (0%) 1.5/6 (25%)
5 to <10 18/26 (69%) 14.7/26 (57%)
10 to <15 30/38 (79%) 31.9/38 (84%)
15 to &l |
