Usage
- Artemether is prescribed for the treatment of acute, uncomplicated malaria infections caused by Plasmodium falciparum, including in geographical regions where resistance to chloroquine has been reported. It is also used for the treatment of severe malaria, particularly when other antimalarials are ineffective. It is effective against the asexual blood stages of P. falciparum, but not against the gametocytes. It is not intended for the prevention of malaria.
- Pharmacological classification: Antimalarial, specifically an artemisinin derivative.
- Mechanism of Action: Artemether is a rapidly acting blood schizonticide. It interferes with the parasite’s ability to detoxify heme, a byproduct of hemoglobin digestion, leading to free radical formation within the parasite and subsequent parasitic death.
Alternate Names
- Artemether is often combined with Lumefantrine and marketed under the brand name Coartem. The injectable formulation may be referred to as Artemether Injection. Riamet is another brand name for the combination of Artemether and Lumefantrine.
How It Works
- Pharmacodynamics: Artemether acts rapidly against the asexual blood stages of P. falciparum, resulting in quick parasite clearance and symptom relief.
- Pharmacokinetics:
- Absorption: Oral artemether is well-absorbed, particularly when taken with fatty food. Intramuscular injection offers rapid absorption for severe cases.
- Metabolism: Artemether is rapidly metabolized in the liver to its active metabolite, dihydroartemisinin (DHA). DHA is further metabolized and eliminated.
- Elimination: Primarily through hepatic metabolism with biliary and renal excretion.
- Mode of Action: Artemether’s endoperoxide bridge is essential for its antimalarial activity. This bridge interacts with heme iron, generating reactive oxygen species that damage parasitic proteins and membranes, ultimately causing parasite death. The rapid action is due to its ability to quickly reach high concentrations within the parasites.
- Receptor Binding/Enzyme Inhibition: The primary mechanism involves heme-mediated free radical formation rather than specific receptor binding or direct enzyme inhibition.
- Elimination Pathways: Hepatic metabolism, with biliary and renal excretion.
Dosage
Standard Dosage
Adults:
- Oral (as part of Artemether-Lumefantrine combination): Four tablets (typically 20mg artemether/120mg lumefantrine per tablet) initially, followed by another four tablets after 8 hours. Then, four tablets twice daily (morning and evening) for the following two days. Total treatment course is 24 tablets over 3 days (six doses). Adults should not use the dispersible tablet.
- Intramuscular Injection: 3.2mg/kg body weight initially, followed by 1.6mg/kg daily for four days. Overweight patients may require dose adjustments.
Children:
- Oral (as part of Artemether-Lumefantrine combination): Dosing is weight-based:
- 5 kg to <15 kg: One tablet initially, followed by another tablet after 8 hours, then one tablet twice daily for two days (total 6 tablets).
- 15 kg to <25 kg: Two tablets initially, followed by another two tablets after 8 hours, then two tablets twice daily for two days (total 12 tablets).
- 25 kg to <35 kg: Three tablets initially, followed by another three tablets after 8 hours, then three tablets twice daily for two days (total 18 tablets).
- Intramuscular Injection: 3.2mg/kg body weight initially, followed by 1.6mg/kg daily for four days.
Special Cases:
- Elderly Patients: No specific dose adjustments are usually needed, but caution is advised for those with significant organ impairment.
- Patients with Renal Impairment: Caution is advised in severe renal impairment, but dosage adjustments may not be routinely necessary.
- Patients with Hepatic Dysfunction: Caution is advised in severe hepatic impairment, but dosage adjustments may not be routinely necessary.
- Patients with Comorbid Conditions: Caution in patients with a history of cardiac arrhythmias, QT prolongation, or electrolyte imbalances.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: Intramuscular artemether may be preferred for initial treatment of severe malaria in these situations due to faster absorption, followed by oral artemether-lumefantrine once the patient can tolerate oral medications.
Dosage Adjustments
- Adjust dosages based on patient weight (particularly in children), renal and hepatic function, and comorbid conditions. Close ECG monitoring is advisable for patients with a risk of QT prolongation.
Side Effects
Common Side Effects
- Headache, dizziness, weakness, fever, chills, tiredness, muscle/joint pain, nausea, vomiting, abdominal pain, cough, trouble sleeping, loss of appetite.
Rare but Serious Side Effects
- Abnormal or fast heartbeat, fainting, rash, hives, difficulty breathing, swelling, severe headache, worsening malaria symptoms, severe vomiting, or inability to eat.
Long-Term Effects
Adverse Drug Reactions (ADR)
- QT prolongation, cardiac arrhythmias, severe skin reactions (rare), and worsening of pre-existing cardiac conditions.
Contraindications
- Hypersensitivity to artemether or lumefantrine.
- First trimester of pregnancy (unless no alternatives are available).
- Concurrent use of drugs metabolized by CYP2D6 (e.g., metoprolol, imipramine, amitriptyline).
- Patients with conditions that prolong the QTc interval or those taking QT-prolonging drugs.
- Severe malaria (for oral formulation; parenteral formulations are used).
Drug Interactions
- CYP450 Interactions: Artemether and lumefantrine are metabolized by CYP3A4. Avoid co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) or inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort).
- QT Prolonging Drugs: Avoid concurrent use with other QT-prolonging drugs (e.g., quinine, quinidine, amiodarone, antipsychotics, macrolide antibiotics, fluoroquinolones).
- Other Interactions: Mefloquine, HIV protease inhibitors, ritonavir.
- Food and Lifestyle Factors: Take with food (preferably fatty food) for optimal absorption. Avoid grapefruit juice.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated in the first trimester unless no other suitable antimalarial is available. Use with caution in the second and third trimesters, weighing the benefits against potential risks.
- Breastfeeding: Breastfeeding is generally not recommended during treatment. If breastfeeding is unavoidable, consider the developmental benefits versus the potential risks of infant exposure to artemether and lumefantrine through breast milk.
Drug Profile Summary
- Mechanism of Action: Rapidly acting blood schizonticide disrupting parasite heme detoxification.
- Side Effects: Headache, dizziness, GI disturbances, fatigue, QT prolongation (rare but serious).
- Contraindications: Hypersensitivity, first trimester of pregnancy, concomitant use of CYP2D6 substrates, QT prolongation risk.
- Drug Interactions: CYP3A4 inhibitors/inducers, QT prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated in the first trimester. Use with caution during breastfeeding.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: ECG (for QT interval), parasite counts, liver function tests.
Popular Combinations
- Artemether is most commonly combined with lumefantrine (Coartem). This combination enhances efficacy and reduces the risk of resistance development. Lumefantrine is a slowly eliminated antimalarial drug, which helps to prevent recrudescence.
Precautions
- Assess for allergies, cardiac history (especially QT prolongation), renal and hepatic function, and concomitant medications.
- Pregnant Women: Avoid use during the first trimester unless essential. Use with caution in later trimesters and closely monitor fetal development.
- Breastfeeding Mothers: Avoid breastfeeding if possible or use with extreme caution, monitoring the infant for any adverse effects.
- Children & Elderly: Dose adjustments based on weight and organ function are essential.
- Lifestyle Considerations: Take with food for optimal absorption; avoid grapefruit juice; counsel patients about potential driving impairment due to dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Artemether?
A: See detailed dosage guidelines above, including adult, pediatric and special populations.
Q2: What is the mechanism of action of Artemether?
A: Artemether acts as a rapid blood schizonticide by interfering with heme detoxification within the malarial parasite. This leads to oxidative stress and parasite death.
Q3: What are the common side effects of Artemether?
A: Common side effects include headache, dizziness, GI disturbances (nausea, vomiting, abdominal pain), fatigue, fever, chills, muscle and joint pain, and sleep disturbances.
Q4: Is Artemether safe during pregnancy?
A: It is contraindicated during the first trimester unless no alternative treatments are available. Use cautiously in the second and third trimesters if the potential benefit outweighs the risk.
Q5: Are there any significant drug interactions with Artemether-Lumefantrine?
A: Yes. Avoid concurrent use of CYP3A4 inhibitors or inducers and drugs that prolong the QT interval. Consult drug interaction resources for a comprehensive list.
Q6: How should Artemether-Lumefantrine be administered?
A: Administer orally with food to enhance absorption. The tablets can be crushed and mixed with water or semi-solid food for young children who cannot swallow tablets whole.
Q7: Can Artemether be used for severe malaria?
A: Yes, intramuscular artemether is used in the treatment of severe malaria, particularly in cases where other antimalarials are ineffective or cannot be administered orally. The intravenous formulation is not recommended.
Q8: Can Artemether-Lumefantrine be used for malaria prophylaxis?
A: No, Artemether-Lumefantrine is not approved for malaria prophylaxis. It is specifically indicated for the treatment of acute, uncomplicated malaria.
Q9: What monitoring is required when administering Artemether?
A: ECG monitoring for QT interval, parasite counts, and liver function tests are recommended.
