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Artemether and Lumefantrine

Medically reviewed by Drugs.com. Last updated on May 7, 2020.

Pronunciation

(ar TEM e ther & loo me FAN treen)

Index Terms

  • Artemether and Benflumetol
  • Artemether/Lumefantrine
  • Benflumetol and Artemether
  • Lumefantrine and Artemether

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:

Coartem: Artemether 20 mg and lumefantrine 120 mg

Brand Names: U.S.

  • Coartem

Pharmacologic Category

  • Antimalarial Agent

Pharmacology

A coformulation of artemether and lumefantrine with activity against Plasmodium falciparum. Artemether and major metabolite dihydroartemisinin (DHA) are rapid schizontocides with activity attributed to the endoperoxide moiety common to each substance. Artemether inhibits an essential calcium adenosine triphosphatase. The exact mechanism of lumefantrine is unknown, but it may inhibit the formation of β-hematin by complexing with hemin. Both artemether and lumefantrine inhibit nucleic acid and protein synthesis. Artemether rapidly reduces parasite biomass and lumefantrine eliminates residual parasites.

Absorption

Artemether: Rapid; Lumefantrine: Initial absorption at 2 hours; enhanced with food

Metabolism

Artemether is hepatically metabolized to an active metabolite, dihydroartemisinin (DHA), catalyzed predominately by CYP3A4/5 and to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. The artemether/DHA AUC ratio is 1.2 after 1 dose and 0.3 after 6 doses which may indicate autoinduction.

Lumefantrine is hepatically metabolized to desbutyl-lumefantrine by CYP3A4.

Time to Peak

Plasma: Artemether: ~2 hours; Lumefantrine: ~6-8 hours

Half-Life Elimination

Artemether: 1-2 hours; DHA: 2 hours; Lumefantrine: 72-144 hours

Protein Binding

Artemether: 95%; Dihydroartemisinin (DHA): 47% to 76%; Lumefantrine: 99.7%

Use: Labeled Indications

Malaria, treatment: Treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum, including geographical regions where chloroquine resistance has been reported. Note: CDC guidelines also recommend artemether/lumefantrine as an alternative agent for chloroquine-sensitive Plasmodium species, for chloroquine-resistant Plasmodium vivax or Plasmodium ovale, and as oral treatment for severe malaria after completion of IV therapy or as interim therapy pending IV therapy (CDC 2020).

Contraindications

Hypersensitivity to artemether, lumefantrine, or any component of the formulation; concurrent use with strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, St John’s wort)

Dosing: Adult

Malaria, treatment: 3-day schedule: Oral:

Patients ≥35 kg: 4 tablets (based on artemether 20 mg/lumefantrine 120 mg per tablet; additional tablet strengths may be available outside the US) at hour 0 and hour 8 on the first day, then 4 tablets twice daily on day 2 and day 3 (total of 24 tablets per treatment course).

Note: If used for P. vivax or P. ovale, use in combination with primaquine. If used for severe malaria (after completion of IV therapy), use full 3-day schedule in addition to IV therapy (CDC 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Malaria, treatment; uncomplicated (due to P. falciparum, including chloroquine resistant P. falciparum): Note: Not for treatment of severe or complicated Plasmodium falciparum malaria or prevention of malaria.

Infants ≥2 months, Children, and Adolescents: Note: Additional tablet strengths may be available outside the US:

Oral (artemether 20 mg/lumefantrine 120 mg per tablet):

5 kg to <15 kg: One tablet at hour 0 and at hour 8 on the first day and then one tablet twice daily (in the morning and evening) on days 2 and 3 (total of 6 tablets per treatment course).

15 kg to <25 kg: Two tablets at hour 0 and at hour 8 on the first day and then two tablets twice daily (in the morning and evening) on days 2 and 3 (total of 12 tablets per treatment course).

25 kg to <35 kg: Three tablets at hour 0 and at hour 8 on the first day and then three tablets twice daily (in the morning and evening) on day 2 and 3 (total of 18 tablets per treatment course).

≥35 kg: Four tablets at hour 0 and at hour 8 on the first day and then four tablets twice daily (in the morning and evening) on days 2 and 3 (total of 24 tablets per treatment course).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Administer with a full meal for best absorption. For patients unable to swallow tablets: Crush tablet and mix with 5-10 mL of water. Administer to patient. Rinse container with water and administer contents to the patient. The crushed mixture should be followed with food/drink if possible. Repeat dose if vomiting occurs within 2 hours of administration; for persistent vomiting, explore alternative therapy.

Dietary Considerations

Administer with a full meal for best absorption. Patients should be encouraged to take with a meal as soon as food can be tolerated. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be great.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Antimalarial Agents: Artemether may enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Antimalarial Agents: May enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): Lumefantrine may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Lumefantrine. Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lumefantrine. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapsone (Systemic): May enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Efavirenz: May decrease the serum concentration of Artemether. Concentrations of dihydroartemisinin (active metabolite of artemether) may also be decreased by efavirenz Monitor therapy

Efavirenz: May decrease the serum concentration of Lumefantrine. Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Estrogen Derivatives (Contraceptive): Artemether may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification

Etravirine: May decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, concentrations of dihydroartemisinin may be decreased. Artemether may increase the serum concentration of Etravirine. Etravirine may increase the serum concentration of Artemether. Monitor therapy

Grapefruit Juice: May increase the serum concentration of Artemether. Monitor therapy

Halofantrine: Lumefantrine may enhance the QTc-prolonging effect of Halofantrine. Management: Halofantrine and lumefantrine (as artemether-lumefantrine combination) should not be used within 1 month of each other. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Mequitazine: Lumefantrine may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to lumefantrine or mequitazine when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Consider therapy modification

Nevirapine: May decrease the serum concentration of Artemether. Nevirapine may also increase or decrease serum concentrations of lumefantrine. Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy

Progestins (Contraceptive): Artemether may decrease the serum concentration of Progestins (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Exceptions: Levonorgestrel (IUD). Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. St John's Wort may decrease the serum concentration of Artemether. Avoid combination

St John's Wort: May decrease the serum concentration of Lumefantrine. Avoid combination

Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Consider therapy modification

Adverse Reactions

>10%:

Cardiovascular: Palpitation (adults: 18%)

Central nervous system: Headache (adults 56%; children 13%), dizziness (adults 39%; children 4%), fever (25% to 29%), chills (adults 23%; children 5%), sleep disorder (adults: 22%), fatigue (adults 17%; children 3%)

Gastrointestinal: Anorexia (adults 40%; children 13%), nausea (adults 26%; children 5%), vomiting (17% to 18%), abdominal pain (8% to 17%)

Infection: Plasmodium falciparum (exacerbation: children: 17%)

Neuromuscular & skeletal: Weakness (adults 38%; children 5%), arthralgia (adults 34%; children 3%), myalgia (adults 32%; children 3%)

Respiratory: Cough (adults 6%; children 23%)

Miscellaneous: Fever (25% to 29%)

3% to 10%:

Central nervous system: Insomnia (adults: 5%), malaise (adults: 3%), vertigo (adults: 3%)

Dermatologic: Pruritus (adults: 4%), skin rash (3%)

Gastrointestinal: Diarrhea (7% to 8%)

Hematologic & oncologic: Anemia (4% to 9%)

Hepatic: Hepatomegaly (6% to 9%), increased serum AST (≤4%)

Infection: Malaria (≤3%)

Respiratory: Rhinitis (4%), nasopharyngitis (≤3%)

<3%, postmarketing, and/or case reports: Abnormal gait, abnormal lymphocytes, abscess, agitation, anaphylaxis, angioedema, asthma, ataxia, back pain, bronchitis, bullous dermatitis, change in platelet count (increased), clonus, conjunctivitis, constipation, decreased hematocrit, decreased platelet count, decreased white blood cell count, dermatitis (hands and feet), dyspepsia, dysphagia, emotional lability, eosinophilia, fine motor control disorder, gastroenteritis, helminthiasis, hematuria, hemolytic anemia (delayed), hookworm infection, hyper-reflexia, hypoesthesia, hypokalemia, impetigo, increased serum ALT, influenza, leukocytosis, leukopenia, lower respiratory tract infection, nystagmus, oral herpes, otic infection, peptic ulcer, pharyngolaryngeal pain, pneumonia, proteinuria, respiratory tract infection, subcutaneous abscess, tinnitus, tremor, upper respiratory tract infection, urinary tract infection, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• QT prolongation: Use associated with prolonging the QT interval; avoid use in patients at risk for QT prolongation, including patients with a history of long QT syndrome, family history of congenital QT prolongation or sudden death, symptomatic arrhythmias, clinically relevant bradycardia, severe heart disease, known hypokalemia, hypomagnesemia or concurrent administration of antiarrhythmics (eg, Class Ia or III), drugs metabolized by CYP2D6 known to have cardiac effects (eg, flecainide, tricyclic antidepressants), or other drugs known to prolong the QT interval (eg, antipsychotics, antidepressants, macrolides, fluoroquinolones, triazole antifungals, or cisapride).

Disease-related concerns:

• Hepatic impairment: Use caution in patients with severe hepatic impairment; has not been adequately studied.

• Renal impairment: Use caution in patients with severe renal impairment; has not been adequately studied.

Concurrent drug therapy issues:

• Drugs that prolong the QT interval: Avoid use in patients receiving other agents that prolong the QT interval; consider alternative therapy. ECG monitoring is advised if concomitant use of agents that prolong the QT interval is medically required. In addition, do not use halofantrine (not available in the US) and artemether/lumefantrine within one month of one another due to the potential additive effects on the QT interval. After discontinuation of artemether/lumefantrine, drugs that prolong the QT interval, including quinidine and quinine, should be used with caution.

• Duplicate therapy: Antimalarials should not be given concomitantly unless there is no other treatment option.

Other warnings/precautions:

• Appropriate use: Not indicated for the treatment of severe or complicated malaria or for the prevention of malaria.

• Recrudescence: In the event of disease reappearance after a quiescent period, patients should be treated with a different antimalarial drug.

Monitoring Parameters

Monitor patients for adequate food consumption (to ensure absorption and efficacy); ECG monitoring is advised if concomitant use of other agents that prolong the QT interval is medically required

Reproductive Considerations

Artemether may reduce the effectiveness of hormonal contraceptives. An additional nonhormonal method of birth control should be used during therapy.

Pregnancy Considerations

A meta-analysis of observational pregnancy studies, which included 500 pregnant women exposed to artemether/lumefantrine in their first trimester, and data from observational and open-label studies of >1,200 pregnant women exposed to artemether/lumefantrine in their second or third trimesters have not shown an increased risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes.

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020; CDC Yellow Book 2020).

Artemether/lumefantrine may be used to treat chloroquine resistant uncomplicated malaria during the second and third trimesters. Artemether/lumefantrine also may be used as an alternative treatment during the first trimester when preferred agents are not available. In pregnant patients with severe malaria, artemether/lumefantrine is the preferred interim oral therapy when the preferred IV agent is not readily available (discontinue once IV treatment is initiated). Dosing is the same as nonpregnant patients (Ballard [CDC 2018]; CDC 2020).

Patient Education

What is this drug used for?

• It is used to treat malaria.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Chills

• Nausea

• Vomiting

• Cough

• Abdominal pain

• Lack of appetite

• Muscle pain

• Joint pain

• Diarrhea

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fast heartbeat

• Abnormal heartbeat

• Severe dizziness

• Passing out

• Severe loss of strength and energy

• Trouble swallowing

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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