SYNRIAM DT

Indications

• Uncomplicated Plasmodium falciparum malaria

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations for paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations for adults based on the clinical scenario.

Mechanism of action

Arterolane functions by inhibiting the biosynthesis of heme in the malaria parasite, leading to toxic accumulation of heme and ultimately, the death of the parasite. It acts as a prodrug, which is converted to its active form in the presence of the parasite's enzymes.

Pharmacodynamics

The pharmacodynamics of arterolane involve its ability to disrupt the life cycle of the malaria parasite. The drug's active metabolites interfere with the parasite's metabolic processes, particularly in the digestion of hemoglobin, which is essential for the survival of the parasite within red blood cells.

Pharmacokinetics

Arterolane is absorbed rapidly following administration, with peak plasma concentrations typically occurring within a few hours. It is metabolized in the liver, primarily via CYP450 enzymes, and has a half-life that supports its use in combination therapies. Elimination is primarily via the urine, with a small fraction excreted unchanged.

Pregnancy

There is limited data on the use of arterolane in pregnancy. Caution is advised when prescribing to pregnant individuals.

Breast-feeding

It is unknown whether arterolane is excreted in human milk. Caution is advised while breastfeeding.

Storage

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

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.