Artemether with lumefantrine

CLINICAL USE

Treatment of malaria

DOSE IN NORMAL RENAL FUNCTION

>35 kg: 6 doses of 4 tablets, i.e. 24 tablets given over 60 hours Give 4 tablets at 0, 8, 24, 36, 48 and 60 hours

PHARMACOKINETICS

Molecular weight : Artemether: 298.4; lumefantrine: 528.9

%Protein binding : Artemether: 95.4; lumefantrine: 99.9

%Excreted unchanged in urine : No data

Volume of distribution (L/kg) : Artemether: 5.4–8.6; lumefantrine: 3.8

half-life – normal/ESRD (hrs) : Artemether 0.8–7; lumefantrine: 48–72 (4–6 days in people with falciparum malaria)

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function. Use with caution

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD : Unknown dialysability. Dose as in GFR <10 mL/min

HD : Unknown dialysability. Dose as in GFR <10 mL/min

HDF/high flux : Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD : Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anti-arrhythmics: avoid concomitant use with amiodarone, disopyramide, flecainide and procainamide – risk of ventricular arrhythmias Antibacterials: avoid concomitant use with macrolides and quinolones.

Antidepressants: avoid concomitant use

Antifungals: avoid concomitant use with imidazoles and triazoles. Antimalarials: increased risk of ventricular arrhythmias with quinine – avoid concomitant use.

Antipsychotics: avoid concomitant use

Antivirals: avoid concomitant use with amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir; possibly increased risk of ventricular arrhythmias with tipranavir – avoid concomitant use Beta-blockers: avoid concomitant use with metoprolol and sotalol

Grapefruit juice: may increase bioavailability and inhibit metabolism – avoid concomitant use Ulcer-healing drugs: avoid concomitant use with cimetidine