Atovaquone
Atovaquone Uses, Dosage, Side Effects, Food Interaction and all others data.
Atovaquone is a hydroxynaphthoquinone, or an analog of ubiquinone, that has antimicrobial and antipneumocystis activity. It is being used in antimalarial protocols.
Atovaquone is a highly lipophilic drug that closely resembles the structure [ubiquinone]. Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. Cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia. There is no significant risk for myelosuppression associated with atovaquone, making this drug a beneficial therapeutic agent for recipients of bone marrow transplantation.
| Trade Name | Atovaquone |
| Availability | Prescription only |
| Generic | Atovaquone |
| Atovaquone Other Names | Atovacuona, Atovaquone |
| Related Drugs | doxycycline, azithromycin, clindamycin, hydroxychloroquine, sulfamethoxazole / trimethoprim, Bactrim, Zithromax, Plaquenil, clarithromycin, Bactrim DS |
| Weight | 750mg/5ml |
| Type | Oral suspension |
| Formula | C22H19ClO3 |
| Weight | Average: 366.837 Monoisotopic: 366.102272181 |
| Protein binding | Atovaquone is extensively bound to plasma proteins (99.9%) over the concentration range of 1 to 90 µg/mL. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Atovaquone is an antimicrobial indicated for the prevention and treatment of Pneumocystis jirovecii pneumonia (PCP) and for the prevention and treatment of Plasmodium falciparum malaria.
For the treatment or prevention of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX). Also indicated for the acute oral treatment of mild to moderate PCP in patients who are intolerant to TMP-SMX.
Atovaquone is also used to associated treatment for these conditions: Malaria caused by Plasmodium falciparum, Pneumocystis Jirovecii Pneumonia, Toxoplasma gondii encephalitis, Acute, uncomplicated Malaria caused by plasmodium falciparum, Mild Babesiosis, Mild Pneumocystis jiroveci pneumonia, Moderate Babesiosis, Moderate Pneumocystis jiroveci pneumonia
How Atovaquone works
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. Atovaquone also has been shown to have good in vitro activity against Toxoplasma gondii.
Toxicity
The median lethal dose is higher than the maximum oral dose tested in mice and rats (1825 mg/kg per day). 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.
Food Interaction
- Take with food. Administration with a meal significantly enhances bioavailability.
[Moderate] ADJUST DOSING INTERVAL: Food, particularly high-fat food, significantly enhances the oral absorption and bioavailability of atovaquone.
In 16 healthy volunteers, administration of a single 750 mg dose of atovaquone suspension following a standard breakfast (23 g fat: 610 kCal) resulted in an approximately 3.4-fold increase in the mean peak plasma concentration (Cmax) and a 2.5-fold increase in the mean area under the plasma concentration-time curve (AUC) of atovaquone compared to administration following an overnight fast.
In a study consisting of 19 HIV-infected volunteers receiving atovaquone suspension 500 mg
MANAGEMENT: To ensure maximal oral absorption, atovaquone products (suspension, tablet, or in combination with proguanil) should be administered with a meal or milky drink, or enteral nutrition at the same time(s) each day.
Because plasma atovaquone concentrations have been shown to correlate with the likelihood of successful treatment and in some cases, survival, alternative therapies may be appropriate for patients who have difficulty taking atovaquone with food.
Atovaquone Drug Interaction
Minor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: mycophenolate mofetil, mycophenolate mofetil, duloxetine, duloxetine, apixaban, apixaban, pregabalin, pregabalin, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, ondansetron, ondansetron, cetirizine, cetirizine
Atovaquone Disease Interaction
Volume of Distribution
- 0.60 ± 0.17 L/kg
Elimination Route
The bioavailability of atovaquone is low and variable and is highly dependent on formulation and diet. Bioavailability of the suspension increases two-fold when administered with meals. When administered with food, bioavailability is approximately 47%. Without food, the bioavailability is 23%.
Half Life
2.2 to 3.2 days
Clearance
- 10.4 +/- 5.5 ml/min [HIV-infected patients receiving IV administration]
Elimination Route
The half-life of atovaquone is long due to presumed enterohepatic cycling and eventual fecal elimination. There was little or no excretion of atovaquone in the urine (less than 0.6%).
Innovators Monograph
You find simplified version here Atovaquone
