Arterolane

Usage

• Arterolane is prescribed for the treatment of acute, uncomplicated Plasmodium falciparum malaria. It is typically administered in combination with piperaquine phosphate.
• Pharmacological classification: Antimalarial.
• Mechanism of action: Arterolane is a synthetic trioxolane, a class of organic peroxides. It exerts its antimalarial activity by generating reactive oxygen species within the parasite. These reactive oxygen species cause damage to vital parasite components, leading to parasite death.

Alternate Names

• International Nonproprietary Name (INN): Arterolane
• Other names: OZ277, RBx11160
• Brand names: Synriam (in combination with piperaquine), Arterakine (in combination with piperaquine)

How It Works

• Pharmacodynamics: Arterolane acts rapidly against all erythrocytic stages of P. falciparum. When combined with the longer-acting piperaquine, it effectively clears parasites from the bloodstream and prevents recrudescence.

• Pharmacokinetics:

  • Absorption: Arterolane is well-absorbed orally, reaching peak plasma concentrations in 2-5 hours. The presence of food does not significantly affect absorption.
  • Metabolism: Arterolane is primarily metabolized by the liver via the cytochrome P450 (CYP3A4) enzyme system.
  • Elimination: Arterolane is rapidly eliminated, with a half-life of 2-4 hours. Piperaquine, on the other hand, has a longer half-life (approximately 2-3 weeks). The elimination pathways for arterolane include both hepatic metabolism and renal excretion.

• Mode of action: Arterolane forms a carbon-centered radical within the parasite, which interacts with heme released from the parasite’s digestion of hemoglobin. This leads to the production of reactive oxygen species which damage the parasitic membranes and macromolecules, leading to cell death.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Arterolane’s primary mode of action involves the generation of free radicals rather than interaction with specific receptors, enzymes, or neurotransmitters.

Dosage

Arterolane is always given in combination with piperaquine. The dosage guidelines below refer to the arterolane component of the combination therapy.

Standard Dosage

Adults:

• 150mg arterolane + 750mg piperaquine once daily for 3 days.
• Administer orally with water, with or without food.

Children:

• The combination of arterolane and piperaquine is available as a dispersible tablet for pediatric use (37.5 mg arterolane + 187.5 mg piperaquine per tablet).
• Pediatric dosing is weight-based and varies according to age group.

Special Cases:

• Elderly Patients: Use with caution due to potential age-related decrease in hepatic and renal function. Monitor closely.
• Patients with Renal Impairment: Use with caution; dose adjustment may be needed.
• Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be needed.
• Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, particularly those with prolonged QT interval.

Clinical Use Cases

Dosage recommendations are specific for acute uncomplicated malaria as described above. Arterolane + Piperaquine is not indicated for use in the following cases:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status epilepticus, cardiac arrest)

Dosage Adjustments

Dose adjustments are not defined for clinical use cases other than uncomplicated malaria, as the drug is not indicated.

Side Effects

Common Side Effects

• Nausea, vomiting, abdominal pain, loss of appetite, indigestion, cough, dizziness, headache, fatigue.

Rare but Serious Side Effects

• Cardiac arrhythmias (including QT prolongation), severe allergic reactions, hepatotoxicity, nephrotoxicity.

Long-Term Effects

Limited data are available on long-term effects.

Adverse Drug Reactions (ADR)

QT prolongation, severe allergic reactions, hepatotoxicity, nephrotoxicity.

Contraindications

• Hypersensitivity to arterolane or piperaquine.
• First trimester of pregnancy.
• Use with caution in patients with known cardiovascular disease, hepatic or renal impairment.

Drug Interactions

• Drugs that prolong the QT interval (e.g., quinine, quinidine, some antipsychotics).
• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) may increase arterolane and piperaquine levels.
• CYP3A4 inducers (e.g., rifampicin, phenytoin) may decrease arterolane and piperaquine levels.
• Antiretroviral drugs (interactions may vary; use cautiously)
• Grapefruit or grapefruit juice may significantly increase piperaquine plasma concentrations.

Pregnancy and Breastfeeding

• Pregnancy: Contraindicated in the first trimester. Use with caution in the second and third trimesters only if the potential benefit outweighs the potential risk to the fetus. May reduce the efficacy of hormonal contraceptives.
• Breastfeeding: Arterolane and piperaquine are present in breast milk. Safety in infants weighing <5kg is unknown. Consider the risks and benefits before use.

Drug Profile Summary

• Mechanism of Action: Generates reactive oxygen species causing parasite death.
• Side Effects: Nausea, vomiting, abdominal pain, QT prolongation (rare).
• Contraindications: Hypersensitivity, first trimester of pregnancy.
• Drug Interactions: QT prolonging drugs, CYP3A4 inhibitors/inducers, antiretrovirals.
• Pregnancy & Breastfeeding: Contraindicated in first trimester of pregnancy. Use with caution during breastfeeding.
• Dosage: 150mg arterolane + 750mg piperaquine once daily for 3 days in adults. Pediatric dosing is weight-based.
• Monitoring Parameters: Monitor for adverse events, particularly cardiac arrhythmias. Parasite counts and fever should be monitored during treatment.

Popular Combinations

• Arterolane is most commonly combined with piperaquine.

Precautions

• Assess for any history of hypersensitivity to the drug.
• Evaluate cardiac, hepatic, and renal function prior to treatment.
• Monitor for QT prolongation, especially in patients with underlying cardiovascular disease or taking other QT-prolonging drugs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Arterolane + Piperaquine?

A: For adults: 150mg arterolane + 750mg piperaquine once daily for 3 days. Pediatric dosing is weight-based.

Q2: How does Arterolane + Piperaquine work?

A: Arterolane rapidly kills malarial parasites, while piperaquine, with its longer half-life, eliminates residual parasites and prevents recurrence.

Q3: What are the most common side effects?

A: Nausea, vomiting, abdominal pain, headache, dizziness.

Q4: Is Arterolane + Piperaquine safe in pregnancy?

A: Contraindicated in the first trimester. Use with caution in later trimesters only if benefits outweigh risks.

Q5: Are there any drug interactions I should be aware of?

A: Yes, it interacts with drugs that prolong the QT interval, CYP3A4 inhibitors/inducers, and some antiretroviral medications.

Q6: Can Arterolane + Piperaquine be used in children?

A: Yes, a dispersible tablet formulation is available for pediatric use, with weight-based dosing.

Q7: What should I monitor in patients taking this medication?

A: Monitor for adverse events, especially cardiac arrhythmias (QT prolongation).

Q8: What if a dose is missed?

A: Take the missed dose as soon as remembered, then continue the remaining doses at the usual intervals. Never double the dose.

Q9: Can it be taken with food?

A: Yes, Arterolane + Piperaquine can be taken with or without food.