MALACUR TABLETS

Indications

• Uncomplicated Plasmodium falciparum malaria
• Malaria in areas with known resistance to other antimalarials

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on weight and age.

Adults: Refer to specific guidelines for dosing as it varies based on formulation and combination therapy.

Mechanism of action

Dihydroartemisinin exerts its antimalarial effects through the activation of endoperoxide bridges in the presence of iron, leading to the formation of free radicals. These free radicals damage the parasite's proteins, lipids, and nucleic acids, ultimately resulting in cell death. The drug is particularly effective during the asexual blood stages of the malaria life cycle.

Pharmacodynamics

Dihydroartemisinin has a rapid onset of action and is effective against both early and late stages of the malaria parasite's life cycle. Its efficacy is enhanced when used in combination with other antimalarial medications, which helps to prevent resistance development. The drug's potency is influenced by factors such as the strain of malaria, the presence of food in the gastrointestinal tract, and the individual's metabolic rate.

Pharmacokinetics

Dihydroartemisinin is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. The bioavailability can be affected by food intake. It undergoes extensive metabolism in the liver, primarily through cytochrome P450 enzymes, leading to various metabolites. The elimination half-life of dihydroartemisinin is relatively short, usually around 1 to 2 hours, necessitating multiple daily doses or combination with longer-acting antimalarials. The drug is primarily excreted in the urine as metabolites.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Headache
• Fatigue
• Anemia
• Rash

Interactions

• May interact with other antimalarial medications
• Potential interactions with drugs that affect liver enzymes
• Caution with concurrent use of anticoagulants

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of hypersensitivity
• Evaluate for potential drug interactions before starting therapy

Pregnancy

Limited data available, use caution and assess risks versus benefits.

Breast-feeding

Limited data available, exercise caution and consult healthcare professionals.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Oral tablets
• Injectable solutions

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.