Usage
- Artesunate + Lumefantrine is prescribed for the treatment of uncomplicated Plasmodium falciparum malaria. This includes treatment of acute episodes and as a prophylactic when travelling to areas with known presence of the parasite. This medication is not effective against severe malaria (e.g., cerebral malaria) which often requires intravenous or intramuscular artesunate.
- Pharmacological Classification: Antimalarial. Specifically, it belongs to the artemisinin-based combination therapies (ACTs).
- Mechanism of Action: Artesunate, a derivative of artemisinin, acts as a rapid-acting schizonticide, targeting the asexual blood stages of P. falciparum, the primary cause of malaria mortality. Lumefantrine, a synthetic aryl amino alcohol, also demonstrates antimalarial activity by inhibiting parasite growth and development within red blood cells. It acts slower than artesunate and is included to eliminate remaining parasites and reduce the risk of treatment failure and recurrence. The combination provides synergistic activity and reduces the likelihood of resistance development.
Alternate Names
- No widely recognized alternate generic names. Artemether-lumefantrine is the most common variation.
- Brand Names: Coartem®, Riamet®.
How It Works
- Pharmacodynamics: Artesunate interferes with parasite protein synthesis and produces free radicals that damage parasite membranes. Lumefantrine inhibits heme polymerization, a crucial process for parasite survival within red blood cells.
- Pharmacokinetics:
- Absorption: Both drugs are lipophilic and absorbed orally. Absorption of lumefantrine is enhanced when taken with fatty food.
- Metabolism: Artesunate is rapidly hydrolyzed to dihydroartemisinin, its active metabolite. Lumefantrine is metabolized primarily by CYP3A4.
- Elimination: Metabolites of both drugs are eliminated mainly through biliary/fecal excretion.
- Mode of Action: Both components target the asexual blood stages of P. falciparum. The exact molecular mechanism of artemisinins is complex, involving the generation of reactive oxygen species and alkylation of parasite proteins. Lumefantrine acts by preventing the formation of hemozoin, a detoxification product of heme metabolism in the malaria parasite.
- Receptor Binding/Enzyme Inhibition: Artesunate interacts with parasite proteins. Lumefantrine inhibits heme polymerase.
- Elimination Pathways: Primarily hepatic metabolism and biliary/fecal excretion for both drugs.
Dosage
Standard Dosage
Adults (≥ 35 kg):
- 4 tablets (20 mg artesunate/120 mg lumefantrine per tablet) as a single initial dose, followed by 4 tablets after 8 hours, and then 4 tablets twice a day (morning and evening) for the following 2 days.
- Total course: 24 tablets (six doses over three days).
- Administer with food, preferably fatty food, to improve lumefantrine absorption.
Children:
Dosage is weight-based:
- 5 kg to <15 kg: 1 tablet per dose x 6 doses (total 6 tablets).
- 15 kg to <25 kg: 2 tablets per dose x 6 doses (total 12 tablets).
- 25 kg to <35 kg: 3 tablets per dose x 6 doses (total 18 tablets).
Special Cases:
- Elderly Patients: No specific dose adjustments are typically required, but monitor for potential adverse effects.
- Patients with Renal Impairment: No dose adjustment is needed.
- Patients with Hepatic Dysfunction: Caution is advised in patients with severe hepatic impairment. Close monitoring is recommended. Dose reduction may be considered in cases of decompensated liver disease.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiac conditions or other significant comorbidities.
Clinical Use Cases
Artesunate plus lumefantrine is specifically indicated for uncomplicated malaria. It is not indicated or recommended for clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments are primarily weight-based in children. No adjustments are typically required in elderly patients or those with renal impairment. Consider dose reduction or close monitoring for those with severe hepatic dysfunction. Adjust dosage based on patient response and tolerance.
Side Effects
Common Side Effects:
- Headache
- Dizziness
- Anorexia
- Nausea
- Vomiting
- Abdominal pain
- Arthralgia
- Myalgia
- Cough
- Insomnia
- Asthenia
- Pyrexia
Rare but Serious Side Effects:
- QT prolongation (mainly with lumefantrine)
- Severe skin reactions (e.g., Stevens-Johnson syndrome)
- Hepatotoxicity (rare)
- Neutropenia
- Anemia
Long-Term Effects:
Limited data exist on long-term effects. Cardiac monitoring may be warranted with prolonged use due to QT prolongation potential.
Adverse Drug Reactions (ADR):
Any signs of cardiotoxicity (e.g., palpitations, syncope, dizziness), severe skin reactions, or signs of severe hepatic dysfunction should be considered serious ADRs requiring prompt evaluation and management.
Contraindications
- Hypersensitivity to artesunate or lumefantrine.
- First trimester of pregnancy.
- Use with caution in second and third trimesters.
- Coadministration with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John’s wort) as these may reduce lumefantrine levels and compromise efficacy.
Drug Interactions
- CYP3A4 Inhibitors/Inducers: Avoid concomitant use with strong CYP3A4 inducers. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) may increase lumefantrine exposure.
- QT Prolonging Drugs: Caution is advised when co-administering with other drugs that prolong the QT interval (e.g., some antiarrhythmics, macrolides).
- Antacids: May reduce absorption; administer at least 2 hours apart.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (second and third trimesters). Contraindicated in the first trimester.
- Fetal Risks: Potential for adverse effects on fetal development during the first trimester. Use with caution in later trimesters if the potential benefit outweighs the risk.
- Breastfeeding: Limited data; use with caution. The amount of drug excreted in breast milk is unknown. It is advisable to discontinue breastfeeding during treatment.
Drug Profile Summary
- Mechanism of Action: Artesunate: rapid-acting schizonticide; Lumefantrine: inhibits heme polymerization.
- Side Effects: Headache, dizziness, GI disturbances, QT prolongation (rare).
- Contraindications: Hypersensitivity, first trimester of pregnancy, strong CYP3A4 inducers.
- Drug Interactions: CYP3A4 modulators, QT prolonging drugs, antacids.
- Pregnancy & Breastfeeding: Category C (second and third trimesters), contraindicated in the first trimester; use with caution during breastfeeding.
- Dosage: Weight-based in children; adults typically receive 4 tablets per dose x 6 doses over 3 days.
- Monitoring Parameters: ECG (for QT interval), liver function tests, complete blood count.
Popular Combinations
Artesunate + Lumefantrine is itself a combination therapy and generally not combined with other antimalarials for uncomplicated malaria. For severe malaria, intravenous artesunate may be combined with other antimalarials.
Precautions
- General Precautions: Assess for any history of cardiac abnormalities or hypersensitivity. Monitor liver function tests and complete blood count during treatment, especially with prolonged use.
- Specific Populations: Adhere to pregnancy and breastfeeding precautions. No special precautions are needed for children or elderly, apart from weight-based dosing for children.
- Lifestyle Considerations: No specific lifestyle restrictions other than advising patients to take the medication with food, particularly fatty foods. No restrictions on driving or operating machinery unless experiencing side effects like dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Artesunate + Lumefantrine?
A: The dosage is weight-based for children (see detailed dosage section above). For adults weighing 35 kg or more, the standard regimen is 4 tablets as a single dose, then another 4 tablets after 8 hours, followed by 4 tablets twice a day for 2 days.
Q2: Can Artesunate + Lumefantrine be used in pregnant women?
A: It is contraindicated in the first trimester. Use with caution in the second and third trimesters only if the potential benefit justifies the potential risk to the fetus.
Q3: What are the most common side effects?
A: Common side effects include headache, dizziness, gastrointestinal symptoms (nausea, vomiting, abdominal pain), and general malaise.
Q4: Are there any serious side effects to be aware of?
A: While rare, QT prolongation (with lumefantrine) can occur and requires monitoring. Severe skin reactions and hepatotoxicity are also rare but potentially serious side effects.
Q5: How should Artesunate + Lumefantrine be taken?
A: The tablets should be taken orally with food, preferably a meal containing fat, as this enhances the absorption of lumefantrine.
Q6: What if a dose is missed?
A: Take the missed dose as soon as remembered. If it is close to the time for the next dose, skip the missed dose and continue the regular dosing schedule. Do not double the dose.
Q7: How does this combination therapy work?
A: Artesunate acts rapidly to reduce the parasite load, while lumefantrine has a slower onset but longer duration of action, clearing remaining parasites and reducing the risk of recurrence.
Q8: Can Artesunate + Lumefantrine be used for all types of malaria?
A: It is specifically indicated for uncomplicated P. falciparum malaria. It is not effective against other malaria species (e.g., P. vivax, P. ovale, P. malariae) or for severe P. falciparum malaria, including cerebral malaria.
Q9: Are there any drug interactions I should be aware of?
A: Yes, avoid co-administration with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine). Caution is advised with other QT prolonging drugs. Antacids may reduce absorption and should be taken at least 2 hours apart.
