P-ALAXIN 80/640MG/80ML SUSPENSION

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria in combination with other antimalarial agents

Dosage

Children: Refer to local guidelines or drug formularies for specific dosing recommendations.

Adults: Refer to local guidelines or drug formularies for specific dosing recommendations.

Mechanism of action

Dihydroartemisinin exerts its antimalarial effect primarily through the generation of reactive oxygen species after iron-mediated cleavage of its endoperoxide bridge. This leads to damage of the parasite's proteins and membranes, ultimately resulting in the death of the malaria parasites. The drug is effective against both the asexual and sexual stages of the malaria lifecycle.

Pharmacodynamics

Dihydroartemisinin is rapidly absorbed and has a short half-life, which contributes to its quick onset of action. It has a high affinity for the malaria parasite, and its efficacy is enhanced when used in combination with other antimalarial agents. The drug's activity is also influenced by the presence of iron in the parasite, which facilitates the activation of the endoperoxide group.

Pharmacokinetics

After oral administration, dihydroartemisinin is rapidly absorbed, with peak plasma concentrations occurring within 2 hours. It undergoes extensive hepatic metabolism, primarily by cytochrome P450 enzymes, resulting in several metabolites. The elimination half-life is approximately 1 to 2 hours, necessitating multiple doses for prolonged efficacy. The drug is excreted mainly in the urine as metabolites.

Contra-indications

• Hypersensitivity to dihydroartemisinin or any of its excipients
• Severe liver impairment
• Severe renal impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Headache
• Fatigue
• Anemia
• Hypotension
• Allergic skin reactions

Interactions

• Caution should be exercised when co-administering with other antimalarial drugs
• Potential interactions with drugs that affect liver enzymes, especially CYP450 inducers and inhibitors

Precautions

• Monitor for signs of hypersensitivity reactions
• Use with caution in patients with a history of liver disease
• Use with caution in patients with a history of cardiac issues
• Ensure accurate diagnosis of malaria before treatment

Pregnancy

Dihydroartemisinin is classified as a Category C drug. It should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dihydroartemisinin is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

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.