Atovaquone/Proguanil Hydrochloride
Atovaquone/Proguanil Hydrochloride 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.
Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase, which is involved in the reproduction of the parasite.
Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against P. falciparum and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.
| Trade Name | Atovaquone/Proguanil Hydrochloride |
| Generic | atovaquone + proguanil |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Mylan |
| Available Country | United Kingdom |
| 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.
Proguanil is a medication indicated for prophylaxis and treatment of Plasmodium falciparum malaria.
For the causal prevention and suppression of malaria caused by susceptible strains of P. falciparum and other species of Plasmodium found in some geographical areas of the world.
Atovaquone/Proguanil Hydrochloride 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 pneumoniaMalaria caused by Plasmodium falciparum, Acute, uncomplicated Malaria caused by plasmodium falciparum
How Atovaquone/Proguanil Hydrochloride 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.
Proguanil inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.
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.
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%.
Rapidly and well absorbed in humans following oral doses ranging from 50 to 500 mg.
Half Life
2.2 to 3.2 days
Approximately 20 hours
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%).
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