COFANTRINE

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria in combination with other antimalarial agents

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Artemeter exerts its antimalarial effects through the generation of reactive oxygen species after being activated by heme, which is released during the digestion of hemoglobin by the malaria parasite. This leads to damage of the parasite's membranes, proteins, and other cellular components, ultimately resulting in cell death. Additionally, artemeter disrupts the parasite's mitochondrial function and interferes with its ability to metabolize essential nutrients.

Pharmacodynamics

The pharmacodynamics of artemeter involve rapid action against the asexual blood stages of the malaria parasite. It has a fast onset of action, typically reducing fever and parasitemia within a few days of treatment. The drug is particularly effective against early-stage malaria infections, and its efficacy is enhanced when used in combination with other antimalarials, which helps to lower the likelihood of developing resistance.

Pharmacokinetics

Artemeter is administered via intramuscular injection or oral routes, with oral bioavailability being relatively variable. It is rapidly absorbed and metabolized in the liver to its active form, dihydroartemisinin. The drug has a half-life of approximately 1 to 2 hours, necessitating multiple doses or combination therapy. It is widely distributed throughout the body and can penetrate the central nervous system. Excretion occurs primarily through urine, with a small proportion eliminated in feces.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Fatigue
• Palpitations
• Hypersensitivity reactions

Interactions

• May interact with other antimalarial agents
• Potential for increased toxicity when used with drugs that affect liver enzymes

Precautions

• Use with caution in patients with liver impairment
• Monitor for signs of hypersensitivity
• Caution in patients with a history of arrhythmias

Pregnancy

Artemeter is classified as a Category C drug. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Artemeter is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Injectable solution
• Oral tablets

Indications

• Uncomplicated malaria due to Plasmodium falciparum
• Coartem (lumefantrine and artemether) for rapid malaria treatment

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, it is suggested that lumefantrine inhibits the formation of beta-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is active against the erythrocytic stages of Plasmodium falciparum. When administered with artemether, it is believed to have cooperative antimalarial effects, with artemether providing rapid symptom relief and lumefantrine clearing residual parasites due to its longer half-life.

Pharmacokinetics

Lumefantrine has a long half-life, allowing for sustained effects after administration. It is absorbed from the gastrointestinal tract and is extensively metabolized in the liver. Its pharmacokinetic profile supports its use in combination therapy with rapidly acting agents like artemether.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Fatigue
• Dizziness
• Palpitations

Interactions

• Drug interactions with artemether; co-administration may enhance antimalarial effects
• Potential interactions with drugs that affect liver enzymes, which may alter lumefantrine metabolism

Precautions

• Use with caution in patients with a history of cardiac arrhythmias
• Monitor for signs of hepatotoxicity in patients with pre-existing liver disease
• Consider potential for drug interactions in patients receiving multiple medications

Pregnancy

Lumefantrine should only be used in pregnancy if clearly needed; consult guidelines for specific considerations.

Breast-feeding

Use with caution while breastfeeding; consult healthcare provider for recommendations.

Storage

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

Formulations

• Tablets
• Oral suspension

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of β-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is a blood schizonticide active against erythrocytic stages of <i>Plasmodium falciparum</i>. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.