Product Information
Registration Status: ActiveSIN09761P
MALARONE TABLET is approved to be sold in Singapore with effective from 1998-05-16. It is marketed by GLAXOSMITHKLINE PTE LTD, with the registration number of SIN09761P.
This product contains Atovaquone 250mg, and Proguanil 100mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by GLAXOSMITHKLINE INC in CANADA, andGLAXO WELLCOME S.A. (Primary and Secondary Packing) in SPAIN.
It is a has been granted the exemption for supply without a presciption if it met certain criteria.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols. [PubChem]
Indication
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.
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. Atovaquone also has been shown to have good in vitro activity against Toxoplasma gondii.
Pharmacokinetics
- Absorption
- 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%.
- Distribution
- * 0.60 ± 0.17 L/kg
- Metabolism
- Some evidence suggests limited metabolism (although no metabolites have been identified).
- Elimination
Clearance
* 10.4 +/- 5.5 ml/min [HIV-infected patients receiving IV administration]
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.
Active Ingredient/Synonyms
2-(trans-4-(P-Chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone | Acuvel | Wellvone | Atovaquone |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
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.
Indication
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.
Mechanism of Action
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.
Pharmacokinetics
- Absorption
- Rapidly and well absorbed in humans following oral doses ranging from 50 to 500 mg.
- Distribution
- Metabolism
- Variably metabolized in the liver by cytochrome P450 isoenzymes to the active triazine metabolite, cycloguanil. This variable metabolism of proguanil may have profound clinical importance in poor metabolizers such as the Asian and African populations at risk for malaria infection. Prophylaxis with proguanil may not be effective in these persons because they may not achieve adequate therapeutic levels of the active compound, cycloguanil, even after multiple doses.
- Elimination
Active Ingredient/Synonyms
N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide | 1-(P-Chlorophenyl)-5-isopropylbiguanide | Chlorguanide | Chloroguanide | N-(4-Chlorophenyl)-n'-(isopropyl)-imidodicarbonimidic diamide | Proguanilum | Proguanil |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.