Usage
Artesunate + Mefloquine is prescribed for the treatment of uncomplicated Plasmodium falciparum malaria. It is an antimalarial drug combination. The mechanism of action involves the synergistic activity of artesunate and mefloquine to inhibit parasite growth and development within red blood cells. Artesunate, an artemisinin derivative, interferes with parasite protein synthesis, while mefloquine inhibits heme polymerization, a process toxic to the parasite.
Alternate Names
- AS + MQ
- Artesunate-Mefloquine
- AS-MQ
- Fixed-dose Artesunate-Mefloquine
How It Works
Pharmacodynamics: Artesunate exerts its parasiticidal effect by generating reactive oxygen species that damage parasite proteins and other vital biomolecules. Mefloquine accumulates in infected red blood cells and disrupts parasite metabolism by inhibiting heme polymerization.
Pharmacokinetics: Artesunate is rapidly absorbed and hydrolyzed to dihydroartemisinin, its active metabolite. Mefloquine is also well-absorbed, but its absorption can be affected by food. Both drugs are metabolized in the liver via CYP450 enzymes and are eliminated primarily through biliary excretion.
Mode of Action: Artesunate and mefloquine work synergistically to eliminate malaria parasites. Artesunate’s rapid action quickly reduces the parasite burden, while mefloquine’s longer half-life provides sustained parasite clearance and prevents recrudescence.
Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Not explicitly discussed for this combination therapy. However, metabolism by CYP450 enzymes is a key factor influencing drug interactions.
Dosage
Standard Dosage
Adults: The total dose over three days is 12 mg/kg artesunate and 25 mg/kg mefloquine. This can be administered as four doses of artesunate at 4mg/kg/day for three days plus mefloquine 8mg/kg/day also for three days.
Children: The total dose over three days is 12 mg/kg artesunate and 25 mg/kg mefloquine. Children ≥6 months and ≥5 kg can receive the adult regimen. Pediatric doses should be calculated precisely based on the child’s weight.
Clinical Use Cases The drug combination is specifically indicated for uncomplicated Plasmodium falciparum malaria. It’s not indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations other than malaria treatment.
Dosage Adjustments
Adjustments are essential in patients with renal or hepatic impairment based on the severity of dysfunction. In patients with hepatic impairment, both artesunate and mefloquine dosages may need reduction. Renal impairment primarily affects mefloquine clearance, necessitating dose adjustments.
Side Effects
Common Side Effects:
Nausea, vomiting, dizziness, headache, abdominal discomfort, loss of appetite, weakness, mild anemia, sleep disturbances.
Rare but Serious Side Effects:
Neuropsychiatric reactions (anxiety, depression, hallucinations, psychosis), seizures, cardiac arrhythmias, severe allergic reactions.
Long-Term Effects: Long-term effects are rare with the standard three-day course. However, neuropsychiatric symptoms may persist in some individuals.
Contraindications
- Hypersensitivity to artesunate or mefloquine
- History of neuropsychiatric disorders (especially psychosis, depression, seizures)
- Pre-existing cardiac conduction abnormalities
- First trimester of pregnancy (relative contraindication)
Drug Interactions
- Antiepileptic drugs (increased risk of seizures)
- Chloroquine or co-artemether (increased risk of seizures and cardiotoxicity)
- Quinine (increased risk of seizures and cardiotoxicity, administer mefloquine 12 hours after last quinine dose)
- Antiarrhythmics, beta-blockers, calcium channel blockers, digitalis (increased risk of cardiac arrhythmias)
- CYP450 enzyme inducers or inhibitors (may alter drug metabolism and clearance)
Pregnancy and Breastfeeding
Pregnancy: Artesunate + Mefloquine is contraindicated in the first trimester and should be used with caution during the second and third trimesters.
Breastfeeding: Mefloquine is excreted in breast milk; weigh the benefits of treatment against potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Synergistic antimalarial activity through inhibition of parasite protein synthesis (artesunate) and heme polymerization (mefloquine).
- Side Effects: Nausea, vomiting, dizziness, headache, neuropsychiatric reactions (rare but serious).
- Contraindications: Hypersensitivity, history of neuropsychiatric disorders, cardiac conduction abnormalities, first trimester of pregnancy.
- Drug Interactions: Antiepileptics, chloroquine, co-artemether, quinine, antiarrhythmics.
- Pregnancy & Breastfeeding: Contraindicated in first trimester; caution during breastfeeding.
- Dosage: Adults/Children: 12 mg/kg artesunate and 25 mg/kg mefloquine over three days.
- Monitoring Parameters: Clinical response, parasite counts, liver function tests, ECG (if indicated).
Popular Combinations Artesunate + Mefloquine is itself a popular fixed-dose combination specifically designed for uncomplicated malaria.
Precautions
Assess renal and hepatic function before initiating treatment, as dosage adjustments may be necessary. Monitor for neuropsychiatric symptoms throughout therapy. Advise patients about potential side effects and interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Artesunate + Mefloquine?
A: The standard dosage is 12 mg/kg artesunate and 25 mg/kg mefloquine given over three days.
Q2: Can Artesunate + Mefloquine be used in pregnancy?
A: It is contraindicated in the first trimester. Use with caution during the second and third trimesters if benefits outweigh risks.
Q3: What are the common side effects of this combination?
A: Common side effects include nausea, vomiting, dizziness, headache, and sleep disturbances.
Q4: What are the serious side effects to watch out for?
A: Neuropsychiatric reactions, cardiac arrhythmias, and severe allergic reactions are rare but serious side effects.
Q5: Are there any drug interactions I should be aware of?
A: Yes, clinically significant interactions exist with certain antiepileptics, antimalarials, and cardiovascular drugs.
Q6: Can Artesunate + Mefloquine be used in patients with renal impairment?
A: Dosage adjustments are necessary in patients with renal impairment, particularly for mefloquine.
Q7: What is the mechanism of action of this drug combination?
A: Artesunate inhibits parasite protein synthesis while mefloquine inhibits heme polymerization, working synergistically to eliminate parasites.
Q8: How should I monitor patients on Artesunate + Mefloquine?
A: Monitor for clinical response, parasite counts, liver function, and cardiac rhythm (if indicated).
Q9: Can this drug be used for severe malaria?
A: No, it’s indicated for uncomplicated P. falciparum malaria. Parenteral artesunate followed by a complete course of another effective oral antimalarial treatment is usually recommended for severe malaria.
Q10: What should I do if a patient experiences vomiting after taking the medication?
A: If vomiting occurs within 30 minutes, repeat the full dose. If vomiting occurs between 30 and 60 minutes, repeat half the dose.
