RIDMAL 40/320

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Combination therapy in malaria treatment
• Treatment for patients with malaria who are unable to take oral medications

Dosage

Children: Refer to specific treatment guidelines and BNF for Children for paediatric dosing information.

Adults: Refer to specific treatment guidelines and BNF for dosing information.

Mechanism of action

Dihydroartemesinin exerts its anti-malarial effects primarily through the generation of reactive oxygen species (ROS) following the cleavage of its endoperoxide bridge in the presence of iron ions from the parasite. This leads to oxidative damage to the parasite's proteins and membranes, ultimately resulting in cell death. The drug is particularly effective in targeting the asexual blood stages of the Plasmodium species.

Pharmacodynamics

The pharmacodynamic profile of dihydroartemesinin includes its rapid onset of action, with a short half-life necessitating multiple doses. Its effectiveness is enhanced when used in combination with other antimalarial drugs, such as piperaquine or lumefantrine, which help to prolong its effects and minimize the likelihood of resistance development. The drug has a demonstrated effect in reducing parasitemia and clinical symptoms of malaria.

Pharmacokinetics

Dihydroartemesinin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours. It undergoes extensive first-pass metabolism in the liver, primarily by cytochrome P450 enzymes, leading to the formation of active metabolites. The elimination half-life is approximately 1-3 hours, necessitating frequent dosing. It is primarily eliminated via hepatic metabolism and renal excretion.

Adverse effects

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

Interactions

• CYP3A4 inhibitors may increase levels of dihydroartemesinin
• CYP3A4 inducers may decrease levels of dihydroartemesinin

Precautions

• Use with caution in patients with liver impairment
• Monitor for signs of hypersensitivity reactions
• Assess for potential drug interactions

Pregnancy

Dihydroartemesinin is classified as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether dihydroartemesinin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure the product is kept out of reach of children.

Formulations

• Oral tablets
• Injectable solution
• Intravenous formulation

Indications

• Plasmodium falciparum malaria
• Uncomplicated malaria
• Treatment of malaria in combination with other antimalarials

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing information.

Adults: Refer to the BNF for specific dosing information based on the treatment regimen and patient condition.

Mechanism of action

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of other antimalarial agents. It is thought to interfere with the parasite's ability to detoxify haem, leading to toxic accumulation within the parasite, thereby inhibiting its growth and replication.

Pharmacodynamics

Piperaquine exhibits a mechanism of action that inhibits the Plasmodium falciparum parasite's haem detoxification pathway. This action is crucial in preventing the survival of the parasite within the host, leading to a reduction in parasitemia and clinical symptoms associated with malaria.

Pharmacokinetics

Piperaquine displays a relatively long half-life, allowing for once-daily dosing in treatment regimens. It is well absorbed following oral administration, with peak plasma concentrations achieved within several hours. The drug is extensively distributed in body tissues, and its elimination involves hepatic metabolism and renal excretion. The pharmacokinetics may be influenced by various drug interactions.

Interactions

• grapefruit juice: Severe (increases concentration)
• mitotane: Severe (decreases concentration)
• St John's Wort: Severe (decreases concentration)
• rifampicin: Severe (decreases concentration)
• dronedarone: Unknown (increases concentration)
• cobicistat: Unknown (increases concentration)
• crizotinib: Unknown (increases concentration)
• idelalisib: Unknown (increases concentration)
• imatinib: Unknown (increases concentration)
• letermovir: Unknown (increases concentration)

Pregnancy

Data on the use of piperaquine in pregnancy are limited. Consult local guidelines for the management of malaria in pregnant women.

Breast-feeding

Piperaquine is excreted in breast milk; caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Piperaquine phosphate tablet

Mechanism of action

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of [DB00608].

Pharmacodynamics

Piperaquine inhibits the P. Falciparum parasite's haem detoxification pathway.