SYNARIUM DT 37.5/187/5MG DISPERSIBLE TABLET

Indications

• Hypertension
• Heart failure
• Edema related to heart disease

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines.

Adults: Refer to specific guidelines or the BNF for exact dosing recommendations for adults.

Mechanism of action

Arterolone selectively binds to the mineralocorticoid receptor (MR) and inhibits the action of aldosterone, a hormone that promotes sodium retention and potassium excretion. This action results in decreased sodium reabsorption in the kidneys, leading to increased diuresis and decreased blood volume, ultimately resulting in lower blood pressure. The drug may also have effects on other pathways involved in the regulation of cardiovascular function.

Pharmacodynamics

The pharmacodynamic effects of arterolone include vasodilation, reduced vascular resistance, and alterations in electrolyte balance, primarily through the inhibition of aldosterone-mediated sodium reabsorption. The resultant decrease in blood volume contributes to the antihypertensive effect observed in patients. The drug's selectivity for the mineralocorticoid receptor minimizes unwanted side effects commonly associated with non-selective agents.

Pharmacokinetics

Arterolone exhibits moderate oral bioavailability with a peak plasma concentration typically occurring within a few hours post-administration. It has a volume of distribution indicating extensive tissue binding. The drug undergoes hepatic metabolism, primarily through cytochrome P450 enzymes, and is excreted in both urine and feces. The half-life allows for once-daily dosing in many cases, but variations may occur based on individual patient factors.

Adverse effects

• Headache
• Dizziness
• Nausea
• Fatigue
• Skin rash

Interactions

• Caution with other CNS depressants
• Potential interaction with anticoagulants
• May alter the effect of antihypertensives

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of CNS depression
• Evaluate for potential drug interactions with concomitant medications

Pregnancy

Arterolone should only be used if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines for use during pregnancy.

Breast-feeding

It is not known if arterolone is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

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

Formulations

• Tablets
• Injectable solution

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.