SYNRIAM TM TABLETS

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Severe malaria
• Malaria prophylaxis in high-risk areas

Dosage

Children: Refer to established clinical guidelines or BNF for Children resources for specific doses.

Adults: Refer to established clinical guidelines or BNF resources for specific doses.

Mechanism of action

Artenolate acts by inhibiting the biosynthesis of heme and interfering with the parasite's ability to detoxify heme, leading to the accumulation of toxic free heme within the parasites. This ultimately causes parasite cell death.

Pharmacodynamics

The pharmacodynamic properties of artenolate include its ability to rapidly reduce the parasitic load in the bloodstream. It exerts a concentration-dependent effect, where higher concentrations lead to more pronounced antimalarial activity. Its action results in a decrease in fever and other symptoms associated with malaria as the parasitic burden decreases.

Pharmacokinetics

Artenolate is absorbed into the bloodstream after oral administration, with peak plasma concentrations typically occurring within a few hours. It is metabolized in the liver and has a half-life that allows for once-daily dosing, making it convenient for patients. The drug is excreted primarily through urine, and factors such as age, liver function, and renal function can influence its pharmacokinetic profile.

Pregnancy

There is limited data on the use of artenolate in pregnancy. It is important to weigh potential benefits against risks.

Breast-feeding

The safety of artenolate during breastfeeding is not well established. Caution is advised.

Storage

Store in a cool, dry place away from 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.