Overview
11 DESCRIPTION Coartem Tablets contain a fixed combination of 2 antimalarial active ingredients, artemether, an artemisinin derivative, and lumefantrine. Both components are blood schizontocides. The chemical name of artemether is (3 R ,5a S ,6 R ,8a S ,9 R ,10 S ,12 R ,12a R )-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3- j ]-1,2-benzodioxepine.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Coartem Tablets, a fixed dose combination of artemether and lumefantrine in the ratio of 1:6, is an antimalarial agent [see Microbiology (12.4)] . 12.3 Pharmacokinetics Absorption Following administration of Coartem Tablets to healthy volunteers and patients with malaria, artemether is absorbed with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with peak plasma concentrations about 6 to 8 hours after administration. The single dose (4 tablets) pharmacokinetic parameters for artemether, DHA, an active antimalarial metabolite of artemether, and lumefantrine in adult Caucasian healthy volunteers are given in Table 3.
Indications
- 1 INDICATIONS AND USAGE Coartem Tablets are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum (P. falciparum) in patients 2 months of age and older with a bodyweight of 5 kg and above. Coartem Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported [see Clinical Studies (14.1)] . Limitations of Use : Coartem Tablets are not approved for patients with severe or complicated P. falciparum malaria. Coartem Tablets are not approved for the prevention of malaria.
Common Doses
- Refer to label
Dosage
2 DOSAGE AND ADMINISTRATION Coartem Tablets should be taken with food. ( 2.1 , 5.2 ) Tablets may be crushed and mixed with 1 to 2 teaspoons of water immediately prior to administration to patients, including children. ( 2.1 ) Coartem Tablets should be administered over 3 days for a total of 6 doses: an initial dose, second dose after 8 hours, and then twice-daily (morning and evening) for the following 2 days. ( 2.2 , 2.3 ) The adult dosage for patients with bodyweight of 35 kg and above is 4 tablets per dose for a total of 6 doses. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity Known hypersensitivity to artemether, lumefantrine, or to any of the excipients of Coartem Tablets [see Adverse Reactions (6.2)] . Strong CYP3A4 Inducers Coadministration of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin, and St. John’s wort with Coartem Tablets can result in decreased concentrations of artemether and/or lumefantrine and loss of antimalarial efficacy [see Warnings and Precautions (5.3), Drug Interactions (7.1), and Clinical Pharmacology (12.3)] .
Side Effects
- 6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling: Hypersensitivity Reactions [see Contraindications (4)] Prolongation of the QT Interval [see Warnings and Precautions (5.1)] Use of QT Prolonging Drugs and Other Antimalarials [see Warnings and Precautions (5.2)] Drug Interactions with CYP3A4 [see Warnings and Precautions (5.3)] Drug Interactions with CYP2D6 [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS CYP3A4 Inducers: Potential for loss of antimalarial efficacy. ( 4 , 5.3 , 7.1 , 12.3 ) CYP3A4 Inhibitors: Use cautiously due to potential for QT prolongation. ( 5.3 , 7.2 , 12.3 ) Antiretrovirals: Use cautiously due to potential for QT prolongation, loss of antiviral efficacy, or loss of antimalarial efficacy of Coartem Tablets. ( 5.3 , 7.3 , 12.3 ) Mefloquine: If used immediately before treatment, monitor for decreased efficacy of Coartem Tablets and encourage food consumption. ( 2.1 , 7.4 , 12.