SYNRIAM 150/750MG TABLET

Indications

• Atrial fibrillation
• Atrial flutter

Dosage

Children: Refer to the BNF for Children for accurate paediatric dosing instructions.

Adults: Refer to specific guidelines or the BNF for precise adult dosing recommendations.

Mechanism of action

Arterone works primarily by blocking potassium channels, particularly the rapid component of the delayed rectifier potassium current (IKr), which prolongs the action potential duration and refractory period in cardiac tissues. Additionally, it exhibits sodium channel blocking properties and has a mild non-selective beta-adrenergic antagonism, which collectively contribute to its antiarrhythmic effects.

Pharmacodynamics

The pharmacodynamics of Arterone involve its ability to reduce the incidence of atrial fibrillation episodes and maintain sinus rhythm. It leads to a decrease in heart rate and modifies conduction through the atrioventricular node. The drug's antiarrhythmic effects are evident through its ability to stabilize cardiac myocyte membranes and alter the electrophysiological properties of the heart.

Pharmacokinetics

Arterone is well absorbed after oral administration with a bioavailability of approximately 60%. It is extensively metabolized in the liver by cytochrome P450 enzymes, primarily CYP3A4, and has a half-life of about 13-19 hours, allowing for once or twice daily dosing. The drug is eliminated through both renal and fecal routes, with its metabolites being excreted predominantly in urine.

Pregnancy

Not enough data available to establish safety during pregnancy. Consult healthcare provider before use.

Breast-feeding

Limited data available. Exercise caution and consult a healthcare provider before use.

Storage

Store at room temperature, away from moisture and heat.

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.