Lumefantrine, an aryl alcohol, is available only as a fixed-dose combination with artemether (Coartem, Riamet), which is now the first-line therapy for uncomplicated falciparum malaria in many countries. In addition, Coartem is approved in many nonendemic countries, including the USA. The half-life of lumefantrine, when used in combination, is 3–4 days. Drug levels may be altered by interactions with other drugs, including those that affect CYP3A4 metabolism. Oral absorption is variable and improved when the drug is taken with food. Since lumefantrine is not associated with the toxicity concerns of halofantrine, Coartem should be administered with fatty food to maximize antimalarial efficacy. Coartem is highly effective in the treatment of falciparum malaria when administered twice daily for 3 days. Coartem can cause minor prolongation of the QT interval, but this appears to be clinically insignificant, and the drug does not carry the risk of dangerous arrhythmias seen with halofantrine and quinidine. Coartem is very well tolerated. The most commonly reported adverse events have been gastrointestinal disturbances, headache, dizziness, rash, and pruritus, and in many cases these toxicities may have been due to underlying malaria or concomitant medications rather than to Coartem.
Pyronaridine, a Mannich base acridine, has been studied as an antimalarial for many years and used as monotherapy in China. It is now available in combination with artesunate as Pyramax. Pyronaridine is well absorbed orally without important food effects. It has a half life of about 8 days, with primarily renal elimination. Artesunate-pyronaridine has generally demonstrated excellent efficacy against falciparum and vivax malaria, although a recent report showed lower efficacy in Cambodia. It has generally been well tolerated. Adverse events have included eosinophilia and transaminitis. A general recommendation for use of artesunatepyronaridine to treat malaria awaits further evaluation of efficacy in children and of potential hepatic toxicity.
Amebiasis is infection with Entamoeba histolytica. This organism can cause asymptomatic intestinal infection, mild to moderate colitis, severe intestinal infection (dysentery), ameboma, liver abscess, and other extraintestinal infections. The choice of drugs for amebiasis depends on the clinical presentation (Table 52–5).
Treatment of Specific Forms of Amebiasis 1.
Asymptomatic intestinal infection—Asymptomatic carriers generally are not treated in endemic areas, but in nonendemic areas they are treated with a luminal amebicide. A tissue amebicidal drug is unnecessary. Standard luminal amebicides are diloxanide furoate, iodoquinol, and paromomycin. Each drug eradicates carriage in about 80–90% of patients. Therapy with a luminal amebicide is also required in the treatment of all other forms of amebiasis.
2.
Amebic Colitis—Metronidazole plus a luminal amebicide is the treatment of choice for amebic colitis and dysentery. Tetracyclines and erythromycin are alternative drugs for moderate colitis but are not effective against extraintestinal disease. Dehydroemetine or emetine can also be used, but are best avoided because of toxicity.
3.
Extraintestinal Infections—The treatment of choice for extraintestinal infections is metronidazole plus a luminal amebicide. A 10-day course of metronidazole cures over 95% of uncomplicated liver abscesses. For unusual cases in which initial therapy with metronidazole has failed, aspiration of the abscess and the addition of chloroquine to a repeat course of metronidazole should be considered. Dehydroemetine and emetine are toxic alternative drugs.