Usage
Arteether is an antimalarial drug prescribed for the treatment of severe Plasmodium falciparum malaria, including cerebral malaria. It is also used as a second-line treatment for chloroquine-resistant malaria. Its pharmacological classification is as an antimalarial agent, specifically within the artemisinin group of drugs. It acts as a blood schizonticide, targeting the asexual blood stages of the P. falciparum parasite.
Alternate Names
Arteether is also known as alpha-beta arteether. Brand names include Artebeta and Athemax.
How It Works
Pharmacodynamics: Arteether works by generating free radicals within the malaria parasite. This process damages the parasite’s cell membranes and disrupts its critical functions, leading to parasite death. The drug specifically targets the erythrocytic stage of the parasite’s life cycle, when it resides within red blood cells. By eliminating these parasites, arteether prevents the disease from progressing.
Pharmacokinetics: Arteether is administered intramuscularly. It is rapidly absorbed and metabolized, primarily by the liver. Though the exact metabolic pathways are not fully elucidated, evidence suggests involvement of the CYP3A4 enzyme. The drug is eliminated primarily through hepatic routes, with a smaller portion excreted renally.
Mode of Action: Arteether’s endoperoxide bridge is cleaved in the presence of the iron-rich environment within the malaria parasite. This generates reactive oxygen species (free radicals), which cause oxidative damage to the parasite’s proteins and lipids, disrupting cellular function and ultimately leading to parasite death.
Receptor Binding/Enzyme Inhibition: The primary mechanism is not through receptor binding or direct enzyme inhibition but rather via free radical generation, as described above. Although, some research indicates possible interaction with membrane channel proteins.
Elimination: Primarily hepatic, partially renal.
Dosage
Arteether is administered via intramuscular (IM) injection.
Standard Dosage
Adults:
150 mg IM once daily for 3 consecutive days.
Children:
3 mg/kg IM daily for 3 consecutive days.
Special Cases:
- Elderly Patients: No specific dosage adjustments are outlined in the available literature, but caution is advised due to potential age-related decline in organ function.
- Patients with Renal Impairment: Use with caution. Dosage adjustments may be necessary in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Use with caution. Dosage adjustments may be necessary in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: No explicit guidelines exist for specific comorbid conditions. Clinical judgment is advised.
Clinical Use Cases
Dosage in specific clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is not explicitly defined. The standard dosing regimen is generally followed.
Dosage Adjustments:
Dose modifications are based on clinical judgment and patient-specific factors, including renal or hepatic dysfunction.
Side Effects
Common Side Effects:
Nausea, dizziness, headache, vomiting, abdominal pain, cough, trouble sleeping, pain at the injection site.
Rare but Serious Side Effects:
Neurotoxicity (gait disturbances, loss of spinal cord responses, incoordination, respiratory depression, convulsions, cardio-respiratory arrest), cardiotoxicity (QT prolongation, arrhythmias)., neutropenia, elevated liver enzymes.
Long-Term Effects:
Limited data are available on long-term effects.
Adverse Drug Reactions (ADR):
Any sign of neurotoxicity or cardiotoxicity requires immediate medical attention.
Contraindications
Hypersensitivity to artemisinin derivatives. First trimester of pregnancy (except in life-threatening situations where no other suitable antimalarial is available).
Drug Interactions
Arteether may interact with drugs metabolized by CYP3A4 (inducers like rifampicin and carbamazepine; inhibitors like ketoconazole, HIV protease inhibitors). It should be used cautiously with QT-prolonging drugs (amiodarone, sotalol, quinine, quinidine). Concomitant use with other artemisinin derivatives (artesunate, artemether) is generally avoided. Interactions with mefloquine, halofantrine, and quetiapine have been reported.
Pregnancy and Breastfeeding
Arteether should not be used during the first trimester of pregnancy unless absolutely necessary due to the potential risk to the fetus. Use in the second and third trimesters should be considered only if the benefit to the mother outweighs the risk to the fetus. It’s unknown whether arteether is excreted in breast milk. Caution is advised, and breastfeeding may need to be interrupted during treatment.
Drug Profile Summary
- Mechanism of Action: Generates free radicals within the malaria parasite, leading to its death.
- Side Effects: Nausea, dizziness, headache, vomiting, abdominal pain; rarely: neurotoxicity, cardiotoxicity.
- Contraindications: Hypersensitivity to artemisinin derivatives, first trimester of pregnancy.
- Drug Interactions: CYP3A4 inducers/inhibitors, QT-prolonging drugs.
- Pregnancy & Breastfeeding: Avoid in the first trimester; caution in other trimesters. Caution during breastfeeding.
- Dosage: Adults: 150 mg IM daily for 3 days; Children: 3 mg/kg IM daily for 3 days.
- Monitoring Parameters: Monitor for signs of neurotoxicity and cardiotoxicity (e.g., ECG for QT prolongation). Liver function tests and complete blood counts should also be monitored.
Popular Combinations
Arteether is not typically used in combination with other artemisinin derivatives. It can be used with other antimalarials like quinine, but caution is needed due to potential drug interactions.
Precautions
Screen for allergies and assess hepatic and renal function before administering. Exercise caution in pregnant and breastfeeding women, children, and the elderly. Patients should avoid driving or operating machinery if dizziness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Arteether?
A: Adults: 150 mg IM once daily for 3 consecutive days; Children: 3 mg/kg IM daily for 3 days.
Q2: What are the common side effects?
A: Nausea, dizziness, headache, and pain at the injection site are common.
Q3: What are the serious side effects to watch out for?
A: Neurotoxicity (difficulty walking, loss of coordination, convulsions) and cardiotoxicity (irregular heartbeat, QT prolongation) are rare but serious.
Q4: Can Arteether be used in pregnancy?
A: Avoid in the first trimester unless absolutely necessary. Use with caution in later trimesters if the benefit outweighs the risks.
Q5: Can Arteether be used during breastfeeding?
A: Caution is advised as it is unknown if arteether is excreted in breast milk. Breastfeeding may need to be interrupted during treatment.
Q6: What drugs interact with Arteether?
A: CYP3A4 inducers/inhibitors and QT prolonging drugs may interact.
Q7: How does Arteether work?
A: It produces free radicals within the malaria parasite, damaging its cell membranes and leading to its death.
Q8: What are the contraindications?
A: Hypersensitivity to artemisinin derivatives and the first trimester of pregnancy.
Q9: How is Arteether administered?
A: Intramuscular (IM) injection.
Q10: What should be monitored in patients receiving Arteether?
A: Monitor for signs of neurotoxicity, cardiotoxicity (ECG), liver function, and complete blood counts.
