In a rat study with doses of 10 and 250 mg/kg given orally by gavage on postpartum Day 11, atovaquone concentrations in the milk were 30% of the concurrent atovaquone concentrations in the maternal plasma at both doses. The concentration of drug in animal milk does not necessarily predict the concentration of drug in human milk.
Evidence of safety and effectiveness in pediatric patients (aged 12 years and younger) has not been established. In a trial of atovaquone oral suspension administered once daily with food for 12 days to 27 HIV-1-infected, asymptomatic infants and children aged between 1 month and 13 years, the pharmacokinetics of atovaquone were age-dependent. The average steady-state plasma atovaquone concentrations in the 24 subjects with available concentration data are shown in Table 5.
|Age||Dose of Atovaquone Oral Suspension|
|10 mg/kg||30 mg/kg||45 mg/kg|
|Average Css in mcg/mL (mean ± SD)|
|Css = Concentration at steady state.|
|1 to 3 months||5.9 (n = 1)||27.8 ± 5.8 (n = 4)||–|
|>3 to 24 months||5.7 ± 5.1 (n = 4)||9.8 ± 3.2 (n = 4)||15.4 ± 6.6 (n = 4)|
|>2 to13 years||16.8 ± 6.4 (n = 4)||37.1 ± 10.9 (n = 3)||–|
Clinical trials of atovaquone did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.
Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose. There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable.
Atovaquone oral solution is a quinone antimicrobial drug. The chemical name of atovaquone is trans -2-[4-(4- chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione. Atovaquone is a yellow crystalline solid that is practically insoluble in water. It has a molecular weight of 366.84 and the molecular formula C 22 H 19 ClO 3 . The compound has the following structural formula:
Atovaquone oral suspension is a formulation of micro-fine particles of atovaquone.
Each 5 mL of atovaquone oral suspension, USP contains 750 mg of atovaquone and the inactive ingredients benzyl alcohol, flavor, hypromellose poloxamer, purified water, saccharin sodium, and xanthan gum.
Atovaquone is a quinone antimicrobial drug [see Microbiology (12.4)] .
Relationship between Plasma Atovaquone Concentrations and Clinical Outcome
In a comparative clinical trial, HIV/AIDS subjects received atovaquone tablets 750 mg 3 times daily or TMP-SMX for treatment of mild-to-moderate PCP for 21 days [see CLINICAL STUDIES (14.2)] ; the relationship between atovaquone plasma concentrations and successful treatment outcome from 113 of these subjects for whom both steady-state drug concentrations and outcome data were available is shown in Table 6.
|Steady-State Plasma Atovaquone Concentrations (mcg/mL)||Successful Treatment *No. of Successes/No. in Group (%)|
|0 to <5||0/6 (0%)|
|5 to <10||18/26 (69%)|
|10 to <15||30/38 (79%)|
|15 to <20||18/19 (95%)|
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