Usage
- Arterolane + Piperaquine is prescribed for the treatment of acute, uncomplicated Plasmodium falciparum malaria in adults and children.
- Pharmacological classification: Antimalarial, Artemisinin-based Combination Therapy (ACT).
- Mechanism of Action: Arterolane, a synthetic trioxolane, acts rapidly to clear parasites by generating reactive oxygen species within the parasite’s food vacuole, damaging vital biomolecules. Piperaquine, a bisquinoline, acts more slowly and provides longer-lasting parasite clearance, preventing recrudescence.
Alternate Names
- Synriam (Brand name in India and several African countries)
- Eurartesim (International brand name)
How It Works
- Pharmacodynamics: Arterolane exerts rapid schizontocidal activity against P. falciparum, leading to quick symptom relief. Piperaquine has a slower onset of action but a longer half-life, providing sustained parasite clearance.
- Pharmacokinetics:
- Arterolane: Well-absorbed orally, reaching peak plasma concentration (Tmax) in 4.5-5.25 hours. Metabolized primarily by CYP3A4 enzymes and eliminated quickly (half-life ~1 hour).
- Piperaquine: Good oral absorption, Tmax 2.5-4.5 hours. Food enhances absorption. Metabolized primarily by CYP3A4, with a long elimination half-life (around 22 days).
- Mode of Action: Arterolane forms reactive oxygen species within the parasite’s food vacuole, disrupting essential biological processes. Piperaquine inhibits parasite heme detoxification, leading to toxic heme accumulation within the parasite.
- Elimination Pathways: Both drugs are primarily metabolized by hepatic CYP3A4 enzymes, with minimal renal excretion of unchanged drug.
Dosage
Standard Dosage
Adults:
- One tablet (Arterolane 150mg + Piperaquine 750mg) once daily for three consecutive days.
Children (6 months to 12 years):
- A dispersible tablet formulation (Arterolane 37.5mg/187.5mg + Piperaquine 187.5 mg/937.5 mg) is available. Dosage is based on weight, and should be taken for 3 consecutive days with food.
- Safety and efficacy have been established in pediatric clinical trials.
Special Cases:
- Elderly Patients: Use with caution; consider renal/hepatic function.
- Patients with Renal Impairment: Use with caution in moderate to severe impairment.
- Patients with Hepatic Dysfunction: Use with caution in moderate to severe impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiac disease, especially those with prolonged QT interval or taking QT-prolonging medications.
Clinical Use Cases
- Arterolane + Piperaquine is specifically indicated for uncomplicated malaria. It’s not recommended for severe malaria, which requires parenteral therapy. Dosages for specific medical settings like intubation, surgical procedures, or ICU use are not relevant as the drug is for oral administration in uncomplicated cases.
Dosage Adjustments
- Adjustments may be needed in patients with moderate to severe renal or hepatic impairment.
Side Effects
Common Side Effects:
- Nausea, vomiting, abdominal pain
- Loss of appetite
- Cough
- Dizziness, headache
Rare but Serious Side Effects:
- QT prolongation (monitor ECG in at-risk patients)
- Hepatotoxicity (monitor liver function)
Long-Term Effects:
- Limited data available on long-term effects.
Adverse Drug Reactions (ADR):
- Severe allergic reactions (rare).
- Significant QT prolongation requiring intervention.
Contraindications
- Hypersensitivity to arterolane, piperaquine, or any component of the formulation.
- Patients with congenital long QT syndrome, or a family history of QT prolongation.
- Concomitant use with other QT-prolonging drugs.
- Severe malaria.
Drug Interactions
- Drugs that inhibit or induce CYP3A4 can alter the metabolism of both arterolane and piperaquine.
- Avoid concomitant use with other antimalarials, especially those that prolong the QT interval (e.g., halofantrine, quinine, quinidine).
- Caution with other QT-prolonging agents (e.g., some antiarrhythmics, antipsychotics, antidepressants, antibiotics).
- Grapefruit juice can increase piperaquine levels.
Pregnancy and Breastfeeding
- Pregnancy: Limited data available. Not recommended in the first trimester. May be used in the second and third trimesters if the benefit outweighs the risk.
- Breastfeeding: Piperaquine is excreted in breast milk. Use with caution; monitor the infant for adverse effects.
Drug Profile Summary
- Mechanism of Action: Arterolane: Generates reactive oxygen species; Piperaquine: Inhibits heme detoxification.
- Side Effects: Nausea, vomiting, abdominal pain, headache, dizziness, QT prolongation (rare).
- Contraindications: Hypersensitivity, long QT syndrome, concomitant QT prolonging drugs.
- Drug Interactions: CYP3A4 inhibitors/inducers, other antimalarials, QT-prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution; limited data.
- Dosage: Adults: One tablet daily for 3 days; Children: Dispersible tablets, weight-based dosing.
- Monitoring Parameters: ECG (for QT interval), Liver function tests.
Popular Combinations
Arterolane and piperaquine are typically prescribed together as a fixed-dose combination, and currently there are not other clinically significant combinations.
Precautions
- Screen patients for cardiac conditions, electrolyte imbalances, and concomitant medications that may prolong the QT interval.
- Assess liver and kidney function.
- Monitor for adverse events, particularly during the first few days of treatment.
- Avoid alcohol during treatment as its interaction with the medication is unknown.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Arterolane + Piperaquine?
A: Adults: One tablet (150mg/750mg) daily for three days. Children: Dispersible tablets, weight-based dosing for three days.
Q2: What are the common side effects of Arterolane + Piperaquine?
A: Nausea, vomiting, abdominal pain, dizziness, headache, cough and loss of appetite.
Q3: Can Arterolane + Piperaquine be used in pregnancy?
A: Limited data. Not recommended in the first trimester. Can be considered in the second and third trimesters if potential benefit justifies the risk.
Q4: Are there any drug interactions with Arterolane + Piperaquine?
A: Yes. Avoid co-administration with other antimalarials and drugs that prolong the QT interval. CYP3A4 inhibitors/inducers can alter drug levels.
Q5: Can Arterolane + Piperaquine be used in patients with renal or hepatic impairment?
A: Use with caution in moderate to severe renal or hepatic impairment. Dosage adjustments may be needed.
Q6: How does Arterolane + Piperaquine work?
A: Arterolane rapidly kills malaria parasites by generating free radicals. Piperaquine has a slower, longer-lasting effect by inhibiting heme detoxification in the parasite.
Q7: What is the treatment duration for Arterolane + Piperaquine?
A: Three consecutive days.
Q8: Can Arterolane + Piperaquine be used for severe malaria?
A: No. It’s only indicated for acute uncomplicated malaria. Severe malaria requires parenteral therapy.
Q9: What should be monitored during Arterolane + Piperaquine treatment?
A: Monitor for adverse events, especially QT prolongation. Monitor ECG in patients at risk. Liver function tests are also recommended.
