CHEMISTRY & PHARMACOKINETICS: Artemisinin and its analogs are rapidly absorbed, with peak plasma levels occurring in 1–2 hours and half-lives of 1–3 hours after oral administration. Artemisinin, artesunate, and artemether are rapidly metabolized to the active metabolite dihydroartemisinin. Drug levels appear to decrease after a number of days of therapy.
Artemether-lumefantrine (Coartem, Lumartem, Combiat, Riamet): Co-formulated; first-line therapy in many countries; approved in the USA
Artesunate-amodiaquine (ASAQ, Arsucam, Coarsucam): Co-formulated; first-line therapy in many African countries
Artesunate-mefloquine: Co-formulated; first-line therapy in parts of Southeast Asia and South America.
Dihydroartemisinin-piperaquine (Artekin, Duocotecxin): Co-formulated; first-line therapy in some countries in Southeast Asia
Artesunate-sulfadoxine-pyrimethamine: First-line therapy in some countries, but efficacy lower than other regimens in most areas.
CLINICAL USES: Artemisinin-based combination therapy is now the standard for treatment of uncomplicated falciparum malaria in nearly all areas endemic for falciparum malaria. These regimens were developed because the short plasma half-lives of the artemisinins led to unacceptably high recrudescence rates after short-course therapy, which were reversed by inclusion of longer-acting drugs. Combination therapy also helps to protect against the selection of artemisinin resistance. However, with completion of dosing after 3 days, the artemisinin components are rapidly eliminated, and so selection of resistance to partner drugs is of concern. The WHO recommends five artemisinin-based combinations for the treatment of uncomplicated falciparum malaria. One of these, artesunate-sulfadoxine-pyrimethamine is not recommended in many areas owing to unacceptable levels of resistance to sulfadoxine-pyrimethamine, but it is the first-line therapy in some countries in Asia, South America, and North Africa. The other four recommended regimens are now all available as combination formulations, although manufacturing standards may vary. Artesunate-mefloquine is highly effective in Southeast Asia, where resistance to many antimalarials is common; it is the first-line therapy in some countries in Southeast Asia and South America. This regimen is less practical for other areas, particularly Africa, because of its relatively high cost and poor tolerability. Either artesunate-amodiaquine or artemether-lumefantrine is now the standard treatment for uncomplicated falciparum malaria in most countries in Africa and some additional endemic countries on other continents. Dihydroartemisinin-piperaquine is a newer regimen that has shown excellent efficacy; it is the first-line therapy for falciparum malaria in Vietnam. T he relative efficacy and safety of artemisinin-based combination therapies are now under active investigation. In general, the leading regimens are highly efficacious, safe, and well tolerated, and they are the new standard of care for the treatment of uncomplicated falciparum malaria. Artemisinins are also proving to have outstanding efficacy in the treatment of complicated falciparum malaria. Large randomized trials and meta-analyses have shown that intramuscular artemether has an efficacy equivalent to that of quinine and that intravenous artesunate is superior to intravenous quinine in terms of parasite clearance time and—most important—patient survival. Intravenous artesunate also has a superior side-effect profile compared with that of intravenous quinine or quinidine. Thus, intravenous artesunate will likely replace quinine as the standard of care for the treatment of severe falciparum malaria, although it is not yet widely available in most areas. Artesunate and artemether have also been effective in the treatment of severe malaria when administered rectally, offering a valuable treatment modality when parenteral therapy is not available.
ADVERSE EFFECTS & CAUTIONS: Artemisinins are generally very well tolerated. The most commonly reported adverse effects are nausea, vomiting, diarrhea, and dizziness, and these may often be due to underlying malaria rather than the medications. Rare serious toxicities include neutropenia, anemia, hemolysis, elevated liver enzymes, and allergic reactions. Irreversible neurotoxicity has been seen in animals, but only after doses much higher than those used to treat malaria. Artemisinins have been embryotoxic in animal studies, but rates of congenital abnormalities, stillbirths, and abortions were not elevated, compared with those of controls, in women who received artemisinins during pregnancy. Based on this information and the significant risk of malaria during pregnancy, the WHO recommends artemisininbased combination therapies for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy, intravenous artesunate or quinine for the treatment of severe malaria during the first trimester, and intravenous artesunate for treatment of severe malaria during the second and third trimesters.
RELATED;
1. PENICILLINS
2. AZITHROMYCIN
No comments:
Post a Comment