Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Riamet (Novartis)
tablets containing 20 mg artemether and 120 mg lumefantrine
Approved indication: Falciparum malaria
Australian Medicines Handbook section 5.4.1
Plasmodium falciparum is the malaria parasite which causes most deaths. In many areas the parasite has developed resistance to chloroquine so there is a need to develop alternative treatments for malaria.
Artemisinin is a chemical found in the sweet wormwood (Artemisiaannua), a Chinese herb used in the treatment of fever. Although artemisinin is effective against the parasite the symptoms rapidly recur unless high doses are used. To overcome the problems of monotherapy artemether, a derivative of artemisinin, has been combined with lumefantrine, an anti-malarial drug developed in China. Compared to artemether, lumefantrine has a slower onset of action, but a more sustained effect against the parasite. The combination is more effective than either drug given alone.
Artemether is rapidly absorbed, but lumefantrine does not reach a peak plasma concentration until 6-8 hours after the combined tablet is swallowed. The tablets are taken after meals as food increases absorption. Artemether undergoes extensive first-pass metabolism and is mainly eliminated by the liver. It has a half-life of two hours whereas lumefantrine which is also eliminated by metabolism has a half-life of 4-6 days in infected patients.
As the metabolism of the drugs involves the cytochrome P450 system there are potential interactions with many drugs that are also metabolised by this system. The combination is contraindicated in patients taking drugs metabolised byCYP3A4 (e.g. erythromycin) or CYP2D6 (e.g. imipramine). It should also not be given with drugs, including other anti-malarial drugs, that prolong the QTc interval. Ideally all patients should have an electrocardiogram before and during treatment as prolongation of the QTc interval is a contraindication to treatment.
Although palpitations can occur in 7.5% of patients the commonest adverse effects are headache and dizziness. Many adverse events during treatment could be caused by malaria. They include fever, asthenia, anorexia and abdominal pain. The safety of artemether and lumefantrine in pregnancy is unknown and it is not approved for use in children less than 12 years old.
A regimen of six doses given over 60 hours has been compared with a mefloquine-based regimen in Thailand. Mefloquine was given to 55 patients with acute uncomplicated falciparum malaria and 164 were given artemether and lumefantrine. All the patients given the mefloquine-based regimen were cured within a month, while the cure rate with the combination was 95.5%. There was no significant difference between the treatments in the clearance of parasites from the blood; more than90% of patients had a reduction in parasites by the third day of treatment.1
People travelling to areas where malaria is endemic need to take precautions to reduce the risk of infection (see 'Malaria prevention in the expatriate and long-term traveller' Aust Prescr 2002;25:66-9).Although artemether and lumefantrine tablets are not approved for prophylaxis they may have a role in emergency 'standby' treatment, however this use has not been evaluated. The future of malaria treatment may lie in combination regimens as they can slow the development of resistance. Artemether and lumefantrine tablets are therefore likely to be used for treatment, particularly as the manufacturer will supply the drug to developing countries at a reduced cost.
