Approved April 7, 2009

ARTEMETHER/LUMEFANTRINE
(FDA Category 1P,O)

COARTEM(R) (Novartis Pharmaceuticals Corporation), a fixeddose combination of artemether and lumefantrine (ratio of 1:6) is an antimalarial agent.

DOSING INFORMATION: The dosing regimen is a 3-day course comprising of 6 doses and is weight-based. For adults and children weighing 35 kilograms (kg) and greater, the recommended dose is a single initial dose of 80 milligrams (mg) artemether/480 mg lumefantrine orally, followed by 80 mg artemether/480 mg lumefantrine orally again after 8 hours (hr), and then 80 mg artemether/480 mg lumefantrine orally twice daily (morning and evening) for the next 2 days. For adults and children 25 kg to less than 35 kg, the recommended dose is a single initial dose of 60 milligrams (mg) artemether/360 mg lumefantrine orally, followed by 60 mg artemether/360 mg lumefantrine orally again after 8 hr, and then 60 mg artemether/360 mg lumefantrine orally twice daily (morning and evening) for the next 2 days. For children 15 kg to less than 25 kg, the recommended dose is a single initial dose of 40 mg artemether/240 mg lumefantrine orally, followed by 40 mg artemether/240 mg lumefantrine orally again after 8 hr, and then 40 mg artemether/240 mg lumefantrine orally twice daily (morning and evening) for the next 2 days. For children 5 kg to less than 15 kg, the recommended dose is a single initial dose of 20 mg artemether/120 mg lumefantrine orally, followed by 20 mg artemether/120 mg lumefantrine orally again after 8 hr, and then 20 mg artemether/120 mg lumefantrine orally twice daily (morning and evening) for the next 2 days.

PHARMACOKINETICS: Peak plasma levels occur 6 to 8 hours after administration, with food enhancing absorption. Artemether and lumefantrine are both highly bound to plasma proteins (95.4% and 99.7%, respectively). Metabolism is primarily through the CYP3A4/5 enzyme systems. The elimination half-life of artemether and DHA (metabolite) is about 2 hours; lumefantrine is cleared slower, with a terminal half-life of 3 to 6 days.

CAUTIONS: Contraindicated in patients with a known hypersensitivity to artemether, lumefantrine, or to any of the excipients in the tablets. Artemether/lumefantrine has been associated with QT interval prolongation; caution with concomitant use of other drugs that prolong the QT interval (ie, other antimalarials, CYP3A4 inhibitors) as well as in patients at increased risk for QT interval prolongation. The most common adverse events include headache, anorexia, dizziness, vomiting, arthralgia/myalgia, and asthenia.

FDA APPROVED INDICATIONS: Artemether/lumefantrine is indicated for the treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients greater than 5 kilograms; not indicated for patients with severe or complicated Plasmodium falciparum malaria or for the prevention of malaria.