ARTENAM

Indications

• Uncomplicated malaria caused by Plasmodium falciparum

Dosage

Children: Refer to the BNF for Children for specific dosage guidelines.

Adults: Refer to the BNF for specific dosage guidelines.

Mechanism of action

Betaartemether interacts with ferriprotoporphyrin IX (heme) in the acidic food vacuole of the malaria parasite, leading to the generation of cytotoxic radical species. This interaction is believed to result in the formation of oxygen-centered and carbon-centered radicals, which are toxic to the parasite. The drug is rapidly taken up by parasitized erythrocytes and disrupts nucleic acid and protein synthesis, contributing to its antimalarial effect.

Pharmacodynamics

In the body, betaartemether is metabolized to dihydroartemisinin, the active metabolite that exerts antimalarial effects. The drug operates effectively against the erythrocytic stages of P. falciparum malaria, inhibiting essential biological processes like nucleic acid and protein synthesis. The combination therapy with lumefantrine enhances therapeutic effectiveness, as betaartemether provides rapid relief while lumefantrine helps to clear residual parasites due to its longer half-life.

Pharmacokinetics

Betaartemether is characterized by a rapid onset of action and is quickly cleared from the body. Its pharmacokinetics are influenced by its metabolism to dihydroartemisinin, which contributes to its therapeutic effects. The drug's absorption and distribution are optimized when used in combination with lumefantrine, which maintains effective plasma concentrations over a longer duration.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Dizziness
• Fatigue
• Allergic reactions

Interactions

• May interact with other antimalarial agents
• Potential interactions with drugs that affect liver enzymes

Precautions

• Use with caution in patients with liver impairment
• Monitor for signs of hypersensitivity
• Avoid use in patients with a history of severe allergic reactions

Pregnancy

Safety in pregnancy has not been established. Use only if potential benefits outweigh risks.

Breast-feeding

Artemether is excreted in breast milk. Caution is advised when administering to breastfeeding mothers.

Storage

Store in a cool, dry place, away from direct light. Keep out of reach of children.

Formulations

• Tablets
• Injection

Mechanism of action

Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are then presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. A 2025 systematic review notes Artemether's pharmacological activity is antimalarial.

Pharmacodynamics

In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of <i>P. falciparum</i> by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.