P-ALAXIN DS 80/640

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Combination therapy in malaria treatment
• Treatment for patients with malaria who are unable to take oral medications

Dosage

Children: Refer to specific treatment guidelines and BNF for Children for paediatric dosing information.

Adults: Refer to specific treatment guidelines and BNF for dosing information.

Mechanism of action

Dihydroartemesinin exerts its anti-malarial effects primarily through the generation of reactive oxygen species (ROS) following the cleavage of its endoperoxide bridge in the presence of iron ions from the parasite. This leads to oxidative damage to the parasite's proteins and membranes, ultimately resulting in cell death. The drug is particularly effective in targeting the asexual blood stages of the Plasmodium species.

Pharmacodynamics

The pharmacodynamic profile of dihydroartemesinin includes its rapid onset of action, with a short half-life necessitating multiple doses. Its effectiveness is enhanced when used in combination with other antimalarial drugs, such as piperaquine or lumefantrine, which help to prolong its effects and minimize the likelihood of resistance development. The drug has a demonstrated effect in reducing parasitemia and clinical symptoms of malaria.

Pharmacokinetics

Dihydroartemesinin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-3 hours. It undergoes extensive first-pass metabolism in the liver, primarily by cytochrome P450 enzymes, leading to the formation of active metabolites. The elimination half-life is approximately 1-3 hours, necessitating frequent dosing. It is primarily eliminated via hepatic metabolism and renal excretion.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Headache
• Fatigue
• Anemia
• Abdominal pain

Interactions

• CYP3A4 inhibitors may increase levels of dihydroartemesinin
• CYP3A4 inducers may decrease levels of dihydroartemesinin

Precautions

• Use with caution in patients with liver impairment
• Monitor for signs of hypersensitivity reactions
• Assess for potential drug interactions

Pregnancy

Dihydroartemesinin is classified as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether dihydroartemesinin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure the product is kept out of reach of children.

Formulations

• Oral tablets
• Injectable solution
• Intravenous formulation

Indications

• Magnesium deficiency
• Supplementation in patients with gastrointestinal disorders
• Prevention of migraine headaches
• Management of preeclampsia and eclampsia
• Cardiac arrhythmias

Dosage

Children: Paediatric dosing should be carefully calculated based on weight and specific clinical indications. Refer to established guidelines or the BNF for Children for precise dosing recommendations.

Adults: Dosage varies based on the condition being treated and should be determined by a healthcare professional. Refer to specific prescribing guidelines for adult dosages.

Mechanism of action

Magnesium acts as a cofactor for various enzymatic processes, which are essential for the production of ATP (adenosine triphosphate). It stabilizes the structures of ATP and is involved in the synthesis of DNA and RNA. Magnesium also plays a role in neuromuscular transmission and muscle contraction by regulating calcium influx into cells, thereby influencing muscle excitability and contraction strength.

Pharmacodynamics

The pharmacodynamic effects of magnesium are multifaceted, influencing neuromuscular function and cardiovascular stability. Adequate magnesium levels are crucial for muscle relaxation and may counteract the effects of calcium, which promotes muscle contraction. It also has a role in vasodilation, contributing to the regulation of blood pressure. Magnesium deficiency can lead to symptoms such as muscle cramps, spasms, arrhythmias, and increased anxiety.

Pharmacokinetics

Magnesium is absorbed mainly in the small intestine, with bioavailability influenced by dietary factors and the presence of other minerals. It is distributed throughout the body, with significant concentrations found in bones, muscles, and soft tissues. Renal excretion is the primary route for magnesium elimination, with the kidneys regulating serum magnesium levels. Factors such as age, diet, and health status can affect magnesium metabolism.

Pregnancy

Consult healthcare provider before use; safety during pregnancy has not been established.

Breast-feeding

Consult healthcare provider; potential effects on nursing infants are unknown.

Storage

Store in a cool, dry place, away from direct sunlight and moisture.

Indications

• Hypophosphatemia
• Osteoporosis
• Renal osteodystrophy
• Malnutrition
• Certain metabolic disorders

Dosage

Children: Refer to established guidelines for specific dosing based on condition and clinical judgment.

Adults: Refer to established guidelines for specific dosing based on condition and clinical judgment.

Mechanism of action

Phosphate acts primarily by serving as a vital component in the formation of ATP, which provides energy for cellular processes. It is also involved in the regulation of enzyme activity and cellular signaling pathways. Phosphate is critical for the mineralization of bones and teeth, as it combines with calcium to form hydroxyapatite, the mineral complex that provides structural integrity to bones.

Pharmacodynamics

Phosphate homeostasis is tightly regulated by various hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. It influences the activity of several enzymes and is involved in the buffering of acids and bases in the body. The balance of phosphate is essential for normal physiological functions, and disturbances can lead to conditions such as hypophosphatemia or hyperphosphatemia, affecting muscle function, bone health, and overall metabolism.

Pharmacokinetics

Phosphate is absorbed primarily in the gastrointestinal tract, mainly in the small intestine. It is distributed throughout the body, with significant amounts found in bones and teeth. The kidneys play a crucial role in regulating phosphate levels through filtration and reabsorption. Phosphate can be excreted in urine, and its levels are influenced by dietary intake and hormonal regulation.

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Hyperphosphatemia
• Hypocalcemia
• Soft tissue calcification

Interactions

• Antacids containing aluminum may bind to phosphate
• Calcium supplements may interact with phosphate absorption
• Certain diuretics may affect phosphate levels

Precautions

• Use cautiously in patients with renal impairment
• Monitor serum phosphate levels in patients with parathyroid disorders
• Consider risk of calcification in tissues with high doses

Pregnancy

Phosphate is generally considered safe during pregnancy, but supplementation should be monitored and managed by a healthcare professional.

Breast-feeding

Phosphate is excreted in breast milk, but normal dietary intake is not expected to harm an infant.

Storage

Store in a cool, dry place, away from direct sunlight. Keep tightly closed.

Formulations

• Oral tablets
• Oral solution
• Injectable forms

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.