Product Description.:
Suspension , yellow , citrus
MEPRON (atovaquone) is an antiprotozoal agent. 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.
MEPRON Suspension is a formulation of micro-fine particles of atovaquone. The atovaquone particles, reduced in size to facilitate absorption, are significantly smaller than those in the previously marketed tablet formulation. MEPRON Suspension is for oral administration and is bright yellow with a citrus flavor. Each teaspoonful (5 mL) contains 750 mg of atovaquone and the inactive ingredients benzyl alcohol, flavor, poloxamer 188, purified water, saccharin sodium, and xanthan gum.
Microbiology
Mechanism of Action: Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystis activity. The mechanism of action against Pneumocystis carinii has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and ATP synthesis.
Activity In Vitro: Several laboratories, using different in vitro methodologies, have shown the IC50 (50% inhibitory concentration) of atovaquone against rat P. carinii to be in the range of 0.1 to 3.0 mcg/mL.
Drug Resistance: Phenotypic resistance to atovaquone in vitro has not been demonstrated for P. carinii. However, in 2 patients who developed P. carinii pneumonia (PCP) after prophylaxis with atovaquone, DNA sequence analysis identified mutations in the predicted amino acid sequence of P. carinii cytochrome b (a likely target site for atovaquone). The clinical significance of this is unknown.
INDICATIONS
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.
SIDE EFFECTS
Because many patients who participated in clinical trials with MEPRON had complications of advanced HIV disease, it was often difficult to distinguish adverse events caused by MEPRON from those caused by underlying medical conditions. There were no life-threatening or fatal adverse experiences caused by MEPRON.
PCP Prevention Studies: In the dapsone comparative study of MEPRON Suspension, adverse experience data were collected only for treatment-limiting events. Among the entire population (n = 1,057), treatment-limiting events occurred at similar frequencies in patients treated with MEPRON Suspension or dapsone (Table 6). Among patients who were taking neither dapsone nor atovaquone at enrollment (n = 487), treatment-limiting events occurred in 43% of patients treated with dapsone and 20% of patients treated with MEPRON Suspension (P < 0.001). In both populations, the type of treatment-limiting events differed between the 2 treatment arms. Hypersensitivity reactions (rash, fever, allergic reaction) and anemia were more common in patients treated with dapsone, while gastrointestinal events (nausea, diarrhea, and vomiting) were more common in patients treated with MEPRON Suspension.
