Usage
- Arteether + Lumefantrine is prescribed for the treatment of acute, uncomplicated malaria infections caused by Plasmodium falciparum, including in geographical regions where chloroquine resistance has been reported. It is indicated for patients aged 2 months and older weighing 5 kg and above. It’s noteworthy that this medication is not intended for severe or complicated P. falciparum malaria or for malaria prevention.
- Pharmacological Classification: Antimalarial (Artemisinin-based combination therapy or ACT)
Alternate Names
- Coartem (brand name), Riamet (brand name in Europe)
- Artemether/Lumefantrine
How It Works
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Pharmacodynamics: Arteether + Lumefantrine exerts its antimalarial effect through the combined action of its components. Arteether, an artemisinin derivative, acts rapidly against the asexual blood stages of P. falciparum, leading to rapid parasite clearance. It forms free radicals within the parasite’s food vacuole, causing damage to parasite proteins and membranes. Lumefantrine, an aryl amino alcohol, also acts against the asexual blood stages, but with a slower onset and longer duration of action, contributing to the overall efficacy of the combination and helping prevent recrudescence.
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Pharmacokinetics: Arteether is rapidly absorbed and metabolized to its active metabolite, dihydroartemisinin. Both arteether and dihydroartemisinin have short half-lives. Lumefantrine is more slowly absorbed and has a longer half-lives. Both drugs are extensively metabolized by the liver (CYP3A4), predominantly via hepatic excretion. Food enhances lumefantrine absorption; concurrent administration with fatty meals is recommended to optimize bioavailability.
Dosage
Standard Dosage
Adults: (≥ 35 kg)
- 4 tablets (artemether 80 mg + lumefantrine 480 mg) as a single initial dose, followed by 4 tablets after 8 hours.
- Then, 4 tablets twice daily (morning and evening) for the following 2 days.
- Total course: 24 tablets over 3 days (6 doses).
Children: (5 kg and above)
- Dosage is weight-based, administered over 3 days (6 doses, as with adults):
- 5 kg to <15 kg: 1 tablet per dose
- 15 kg to <25 kg: 2 tablets per dose
- 25 kg to <35 kg: 3 tablets per dose
Special Cases:
- Elderly Patients: No dose adjustments are typically necessary.
- Patients with Renal Impairment: No dose adjustment is generally required. Caution is advised in severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is generally required. Caution is advised in severe hepatic impairment.
Clinical Use Cases
The drug is intended for uncomplicated malaria. It is not indicated for the following:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
No specific dosage adjustments are provided for comorbid conditions, metabolic disorders, or genetic polymorphisms.
Side Effects
Common Side Effects:
- Headache, dizziness, weakness
- Muscle or joint pain, tiredness
- Difficulty sleeping
- Vomiting, loss of appetite, fever, chills
- Cough
Rare but Serious Side Effects:
- QT prolongation, cardiac arrhythmias
- Severe allergic reactions (e.g., hives, angioedema, difficulty breathing)
- Worsening malaria symptoms
Long-Term Effects:
Limited data on long-term effects are available.
Adverse Drug Reactions (ADR):
Contraindications
- Hypersensitivity to artemether, lumefantrine, or any excipients
- Severe malaria (according to WHO definition)
- Concomitant use of drugs metabolized by CYP2D6 (e.g., metoprolol, imipramine, amitriptyline)
- Conditions known to prolong the QTc interval, including congenital long QT syndrome, or concomitant use of QT-prolonging drugs (e.g., some antiarrhythmics, neuroleptics, antidepressants, certain antibiotics).
Drug Interactions
- Drugs metabolized by CYP3A4 (including some antibiotics like erythromycin or ketoconazole): Co-administration may alter levels of either drug.
- Drugs that prolong the QT interval: Increased risk of arrhythmias.
- Mefloquine: May reduce lumefantrine absorption.
- Quinine: May increase the risk of QTc prolongation.
- Halofantrine: Avoid concomitant use or administer at least one month apart.
- Grapefruit juice: Increases artemether exposure.
Pregnancy and Breastfeeding
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Pregnancy: Recommended by WHO for treatment of uncomplicated falciparum malaria during all trimesters of pregnancy. Earlier guidance advised against first-trimester use if alternative treatments were available, due to concerns of embryotoxicity observed in animal studies; newer evidence suggests safety in the first trimester.
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Breastfeeding: Amounts of artemether, dihydroartemisinin, and lumefantrine excreted in breast milk are small. Generally considered acceptable for use during breastfeeding, especially for infants weighing at least 5 kg. Safety in infants under 5 kg is not fully established.
Drug Profile Summary
- Mechanism of Action: Arteether: Rapidly acting schizonticide forming free radicals in the parasite. Lumefantrine: Aryl amino alcohol also active against asexual blood stages, with slower onset and longer duration.
- Side Effects: Common: Headache, dizziness, GI disturbances. Serious: QT prolongation.
- Contraindications: Hypersensitivity, severe malaria, concomitant use of CYP2D6 substrates, conditions prolonging the QT interval.
- Drug Interactions: CYP3A4 interactions, QT prolonging drugs, mefloquine, quinine, halofantrine, grapefruit juice.
- Pregnancy & Breastfeeding: Generally considered safe in all trimesters of pregnancy and during breastfeeding.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: ECG (for QTc interval), especially in patients at risk.
Popular Combinations
- Arteether + Lumefantrine is itself a combination therapy. Fixed-dose combinations with other antimalarials are under development (e.g., with amodiaquine). Avoid concurrent use of other antimalarials unless absolutely necessary.
Precautions
- Ensure correct diagnosis of uncomplicated malaria.
- Administer with food to enhance lumefantrine absorption.
- Monitor for cardiac effects (QTc prolongation).
- Re-administer the dose if vomiting occurs within 1 hour.
- Tablets can be crushed and mixed with water or a small amount of semi-solid food for young children or patients who cannot swallow whole tablets.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Arteether + Lumefantrine?
A: See the detailed dosage guidelines above. Dosage varies by weight for children and is a fixed dose for adults (≥35 kg).
Q2: Can Arteether + Lumefantrine be used during pregnancy?
A: Yes, the WHO recommends Arteether + Lumefantrine for uncomplicated falciparum malaria during all trimesters of pregnancy.
Q3: What are the most common side effects of Arteether + Lumefantrine?
A: Common side effects include headache, dizziness, fever, chills, weakness, fatigue, muscle/joint aches, gastrointestinal disturbances (vomiting, loss of appetite), cough, and sleep disturbances.
Q4: What are the contraindications for Arteether + Lumefantrine?
A: Contraindications include known hypersensitivity, severe malaria, concomitant use of CYP2D6 substrates, and conditions known to prolong the QT interval.
Q5: Are there any important drug interactions with Arteether + Lumefantrine?
A: Yes, significant interactions can occur with drugs metabolized by CYP3A4, QT-prolonging medications, mefloquine, quinine, and halofantrine.
Q6: What should I do if a patient vomits after taking Arteether + Lumefantrine?
A: If vomiting occurs within 1 hour of administration, repeat the dose.
Q7: How is Arteether + Lumefantrine administered to young children or patients unable to swallow tablets?
A: The tablets can be crushed and mixed with a small amount of water or semi-solid food for administration.
Q8: What is the mechanism of action of Arteether + Lumefantrine?
A: Arteether acts quickly against malaria parasites by generating free radicals within the parasite. Lumefantrine acts similarly but with a slower onset and longer duration, helping to prevent the parasite from returning.
Q9: Is it safe to breastfeed while taking Arteether + Lumefantrine?
A: Generally, it is considered safe to breastfeed while taking Arteether + Lumefantrine, particularly if the infant weighs at least 5 kg, as the amount of drug in breastmilk is small. However, the safety in breastfed infants weighing less than 5 kg is not fully established.
