Sulfadoxine and Pyrimethamine act by reciprocal potentiation of its two components, achieved by a sequential blockage of two enzymes involved in the biosynthesis of folic acid in parasites. Artesunate + Sulfadoxine + Pyrimethamine Tablets are a treatment for all forms of malaria due to Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae.
Indications:
Effective For:
● Treatment of toxoplasmosis
● Treatment of acute malaria (in conjunction with a schizonticide will initiate transmission control and suppression of susceptible strains of plasmodia); chemoprophylaxis of malaria.
● For attacks due to Plasmodium falciparum (a particular type of malaria parasite), against which the ingredients are active.
Pharmacology:
Mechanism of Action:
Sulfadoxine and Pyrimethamine:
Sulfadoxine is a sulfa drug, often used in combination with pyrimethamine to treat malaria. This medicine may also be used to prevent malaria in people who are living in, or will be traveling to, an area where there is a chance of getting malaria. Sulfadoxine targets Plasmodium dihydropteroate synthase and dihydrofolate reductase. Sulfa drugs or Sulfonamides are antimetabolites. They compete with para-aminobenzoic acid (PABA) for incorporation into folic acid. The action of sulfonamides exploits the difference between mammal cells and other kinds of cells in their folic acid metabolism. All cells require folic acid for growth. Folic acid (as a vitamin) diffuses or is transported into human cells. However, folic acid cannot cross bacterial (and certain protozoan) cell walls by diffusion or active transport. For this reason bacteria must synthesize folic acid from p-aminobenzoic acid.
Artesunate:
Artesunate is a potent blood schizonticide agent for P. falciparum. It is effective against P. falciparum resistant to all other antimalarial drugs. It does not have hypnozoiticidal activity. It reduces gametocyte carriage rate. Artesunate binds tightly to parasitized erythrocyte membranes. The functional group responsible for antimalarial activity of artesunate is endoperoxide bond. Release of an active oxygen species from this bond kills the parasite if accumulated in the erythrocytic cells. It also suppresses the production or activity of antioxidant enzymes in the erythrocytes, causing lysis of the parasitic cell due to the highly reactive free oxygen radicals.
Pharmacokinetics:
Sulfadoxine and Pyrimethamine:
Absorption: After administration of 1 tablet, peak plasma levels for pyrimethamine (approximately 0.2 mg/L) and for sulfadoxine (approximately 60 mg/L) are reached after about 4 hours. Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Artesunate peak serum levels occur within one hour of an oral dose of artesunate and persist for up to 4 hours.
Distribution: The volume of distribution for sulfadoxine and pyrimethamine is 0.14 L/kg and 2.3 L/kg, respectively.
Metabolism: About 5% of sulfadoxine appears in the plasma as acetylated metabolite, about 2 to 3% as the glucuronide. Pyrimethamine is transformed to several unidentified metabolites.
Excretion: A relatively long elimination half-life is characteristic of both components. The mean values are about 100 hours for pyrimethamine and about 200 hours for sulfadoxine. Both pyrimethamine and sulfadoxine are eliminated mainly via the kidneys. Artesunate has a plasma elimination half-life of less than 2 hours, which may slow the development of resistance.
Adverse Effects:
Fever, frequent urination, eye inflammation, sensitivity to light, sore tongue/mouth, headache, tiredness.
Drug Interactions:
Some products that may interact with this drug include: "blood thinners" (such as warfarin), chloroquine, cyclosporine, drugs that lower folate levels (such as phenytoin, "sulfa" antibiotics, trimethoprim), methenamine, penicillamine, live vaccines such as typhoid vaccine taken by mouth, drugs that may cause a decrease in white blood cells (such as chemotherapy drugs like methotrexate).
Storage:
Store at room temperature away from light and moisture. Keep all medicines away from children.