Suspensions atovaquone

MEPRON suspension is a formulation of microfine 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 

Charge items 4 and 3 in a suitable stainless steel vessel and mix well. 

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Atovaquone suspension 750 mg (5 mL) orally twice daily with meals for 21 days0 (Bl)... 

In a prospective efficacy trial of atovaquone suspension (750 mg od or 250 mg tds for 1 year) in P. jiroveci prophylaxis in 28 liver transplant recipients intolerant of co-trimoxazole, the adverse events reported included diarrhea (n — 7) and bloating or abdominal pain (n — 3) (16). No patient had developed P. jiroveci pneumonia by 37 months. This is a smaller dose than approved for Pneumocystis prophylaxis in HIV infection (1500 mg/day). Further studies in recipients of solid organ transplants are needed to confirm the efficacy of this prophylactic dose. 

Atovaquone suspension (1500 mg orally bd) plus either pyrimethamine (75 mg/day after a 200 mg loading dose) or sulfadiazine (1500 mg qds), as treatment for acute Toxoplasma encephalitis (for 6 weeks) and as maintenance therapy (for 42 weeks), has been studied in a randomized phase II trial in HIV-positive patients (17). There were good responses in 21 of 28 patients who received pyrimethamine and nine of 11 who received sulfadiazine. Of 20 patients in the maintenance phase, only one relapsed. Of 40 eligible patients, 11 discontinued treatment as a result of adverse events, nine because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. 

Atovaquone suspension (750 mg bd n — 34) or tablets (750 mg tds n — 20) have been retrospectively compared in the treatment of P. jiroveci pneumonia in HIV-positive... 

Rosenberg DM, McCarthy W, Slavinsky J, Chan CK, Montaner J, Braun J, Dohn MN, Caldwell PT. Atovaquone suspension for treatment of Pneumocystis carinii pneumonia in HIV-infected patients. AIDS 2001 15(2) 211-14. 

Falloon J, Sargent S, Piscitelli SC, Bechtel C, LaFon SW, Sadler B, Walker RE, Kovacs JA, Polls MA, Davey RT, Lan HC, Masur H. Atovaquone suspension in HIV-infected volunteers pharmacokinetics, pharmacodynamics, and TMP-SMX interaction study. Pharmaco erepy (1999) 19, 1050-6. 

Established interactions of clinical importance. Atovaquone suspension used for the treatment or prevention of Pneumocystis pneumonia must be taken with food, since this is likely to increase the likelihood of successful treatment and survival. Alternatively, an enteral nutritional supplement with a high-fat content appears to be suitable. In the US, the manufacturer says that, for patients who have difficulty taking atovaquone suspension with food, parenteral therapy for Pneumocystis pneumonia should be considered. ... 

Freeman CD, Klutman ME, Lamp KC, Dali LH, Strayer AH. Relative bioavailability of atovaquone suspension when adm inistered with an enteral nutrition siq>plement. Arm Pharma-cother 99Z)32,1004-7. 

Taking atovaquone with fatty food markedly increases its AUC by two to threefold. Atovaquone/proguanil tablets should be taken with food or a milky drink, and atovaquone suspension should be taken with food, to maximise absorption and efficacy. 

In a pharmacokinetic study in HIV-positive subjects designed to determine the dose of atovaquone suspension that would achieve specific steady-state plasma levels, administration with high-fat food increased the bioavailability of atovaquone by 1.4-fold when compared with the fasted state. In another similar study, administration of atovaquone suspension with food (23 g of fat) increased average steady-state levels by 1.3-fold to 1.7-fold with different dosage regimens (using 500 mg to 1.5 g of atovaquone. ... 

The manufacturers suggest that parasitaemia should be closely monitored in patients taking atovaquone/proguanil tablets with tetracycline. In the UK, they also say that tetracycline should be given with caution to patients taking atovaquone suspension for Pneumocystis pneumonia, until the interaction has been further studied, whereas the US manufacturers of atovaquone suspension do not mention tetracycline. ... 

Emmanuel A, Gillotin C, Farinotti R, Sadler BM. Atovaquone suspension and indinavir have minimal pharmacokinetic interactions. IntConfAIDS (1998) 12, 90. 

Atovaquone 1 500 mg suspension by mouth once a day Elevated liver transaminases Nausea Rash... 

CSF concentratons are less than 1% of plasma concentrations. Half-life ranged from 67 to 77.6 hours following the suspension. The long half-life is caused by presumed enterohepatic cycling and eventual fecal elimination. There is indirect evidence that atovaquone may undergo limited metabolism however, a specific metabolite has not been identified. 

Atovaquone is a highly lipophilic compound, which shows considerable inter-individual variability in absorption. Dietary fat increases the rate and extent of atovaquone absorption from both the suspension and the tablets, probably by increasing its solubility in the gut. The suspension has about a twofold higher oral bioavailability than the tablets when given with food or when fasting. 

WeUvone Oral Suspension (Atovaquone). Gl oSmithKUne UK. UK Summary of product characteristics. May 2006. 

Mepr i Suspension (Atovaquone). Gl o)SmilhK]ine. US Prescribii informaticxi, November 2006. 

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