Artemether and lumefantrine (artemether/lumefantrine) is a fixed combination of 2 antimalarial agents;1 artemether is an artemisinin-derivative antimalarial1, 161 and lumefantrine is an aryl aminoalcohol antimalarial.161
Treatment of Uncomplicated Malaria
Artemether and lumefantrine (artemether/lumefantrine) is used in adults and children weighing 5 kg or more for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum , including malaria acquired in areas with chloroquine resistance.1, 3, 4, 5, 6, 7, 8, 143, 144 Artemether/lumefantrine also has been used for the treatment of uncomplicated malaria caused by P. vivax †.1
For the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or the treatment of uncomplicated malaria when the plasmodial species has not been identified, the US Centers for Disease Control and Prevention (CDC) recommends the fixed combination of atovaquone and proguanil (atovaquone/proguanil), artemether/lumefantrine, or a regimen that includes quinine sulfate in conjunction with doxycycline, tetracycline, or clindamycin.143, 144 Although mefloquine is another option for treatment in these patients,143, 144 the CDC recommends that it be used only when other recommended treatment regimens cannot be used.143
For the treatment of uncomplicated malaria caused by chloroquine-susceptible P. falciparum , P. malariae , or P. knowlesi or the treatment of uncomplicated malaria when the plasmodial species has not been identified and the infection was acquired in areas where chloroquine resistance has not been reported, the CDC recommends chloroquine (or hydroxychloroquine).143, 144 Alternatively, the CDC states that any of the regimens recommended for the treatment of uncomplicated chloroquine-resistant P. falciparum malaria may be used if preferred, more readily available, or more convenient.143, 144
Pediatric patients with uncomplicated malaria generally can receive the same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages.143, 144 For the treatment of uncomplicated chloroquine-resistant P. falciparum in children younger than 8 years of age, the CDC recommends atovaquone/proguanil or artemether/lumefantrine; mefloquine can be considered if no other options are available.144 For the treatment of chloroquine-resistant P. vivax malaria in children younger than 8 years of age, the CDC recommends mefloquine given in conjunction with primaquine.143, 144 Alternatively, if mefloquine is not available or not tolerated and if potential benefits outweigh risks, atovaquone/proguanil or artemether/lumefantrine can be used for treatment of chloroquine-resistant P. vivax in this age group.143, 144
Pregnant women with uncomplicated malaria caused by P. malariae , P. vivax , P. ovale , or chloroquine-susceptible P. falciparum should receive prompt treatment with chloroquine (or hydroxychloroquine).143 The CDC recommends that pregnant women with uncomplicated malaria caused by chloroquine-resistant P. falciparum receive prompt treatment with either mefloquine or a regimen of quinine sulfate and clindamycin;143 mefloquine is recommended for those with uncomplicated malaria caused by chloroquine-resistant P. vivax .143 Alternatively, atovaquone/proguanil or artemether/lumefantrine can be considered for the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum in pregnant women when other treatment options are not available or not tolerated and if potential benefits outweigh risks.143 (See Pregnancy under Warnings/Precautions: Specific Populations, in Cautions.)
Patients with severe malaria require aggressive antimalarial treatment with a parenteral regimen of IV quinidine gluconate in conjunction with doxycycline, tetracycline, or clindamycin initiated as soon as possible after the diagnosis.143, 144 (See Uses: Malaria, in Quinidine 24:04.04.04.)
Assistance with diagnosis or treatment of malaria is available by contacting the CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or the CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143, 144
Efficacy of artemether/lumefantrine was evaluated for the treatment of acute, uncomplicated malaria caused by P. falciparum in HIV-negative patients in 8 clinical studies.1 Studies were conducted in partially immune and non-immune adults and children weighing 5 kg or more with uncomplicated malaria in China, Thailand, sub-Saharan Africa, Europe, and South America.1, 4, 5, 6, 7, 8 In studies that used the recommended 6-dose regimen, artemether/lumefantrine was associated with 28-day cure rates (defined as clearance of asexual parasites [the erythrocytic stage] within 7 days without recrudescence by day 28) in 88-97% of evaluable patients; the median time to parasite clearance was 24-44 hours and the median time to resolution of fever was 8-37 hours.1
Efficacy of artemether/lumefantrine for the treatment of mixed infections involving P. falciparum and P. vivax was assessed in 43 patients.1 Although parasitemia was cleared in all patients within 48 hours, relapse occurred in 33%.1 P. vivax malaria requires additional treatment with primaquine to achieve a radical cure (i.e., eradicate hypnozoites that remain dormant in the liver).1 (See Cautions: Selection and Use of Antimalarials.)
Artemether/lumefantrine is one of several artemisinin-based combination therapy (ACT) regimens recommended by the World Health Organization (WHO) for treatment of uncomplicated P. falciparum malaria in countries where the disease is endemic.161 Such regimens reduce malaria transmission in these areas and may delay or prevent emergence of resistance to the drugs contained in the combination regimen.161
Presumptive Self-treatment of Malaria
Travelers who elect not to take chemoprophylaxis for prevention of malaria and travelers who require or choose to use a chemoprophylaxis regimen that may not have optimal efficacy (e.g., chloroquine prophylaxis in areas with chloroquine-resistant P. falciparum ) are at increased risk of acquiring malaria and may need prompt treatment.115 In addition, some travelers who are taking effective prophylaxis but who will be in very remote areas may decide, in consultation with their health-care provider, to take along an appropriate antimalarial that can be used for presumptive self-treatment if necessary.115, 134
The antimalarial regimen provided for presumptive self-treatment should be different than the regimen that the traveler is using for prophylaxis.134 Travelers should be advised to initiate self-treatment promptly in the event of an influenza-like illness (e.g., fever, chills) if professional medical care is not readily available.115, 134 Use of presumptive self-treatment is only a temporary measure and these travelers should be advised that it is imperative that they seek a professional medical evaluation as soon as possible.115
For presumptive self-treatment of malaria† in travelers, the CDC and other experts recommend atovaquone/proguanil or artemether/lumefantrine.115, 134
Artemether/lumefantrine is not approved by the FDA for prevention of malaria.1 The CDC and other clinicians recommend use of other antimalarial agents (e.g., chloroquine [or hydroxychloroquine], atovaquone/proguanil, doxycycline, mefloquine) for prevention or chemoprophylaxis of malaria caused by susceptible Plasmodium .115, 134
Information on the risk of malaria transmission in specific countries, information on mosquito avoidance measures, recommendations regarding whether chemoprophylaxis of malaria is indicated, and information on the choice of antimalarials for prevention are available from the CDC at [Web] and [Web].115
Artemether and lumefantrine (artemether/lumefantrine) is administered orally with food.1 Administration with food increases bioavailability of both drugs.1
For patients who are unable to swallow tablets, artemether/lumefantrine tablets may be crushed and mixed with a small amount of water (5-10 mL) immediately prior to administration.1 The container can be rinsed with more water and the contents swallowed by the patient.1
Each dose of tablets or the crushed tablet preparation should be followed by food or drink (e.g., milk, formula, pudding, broth, porridge).1
If a patient vomits within 1-2 hours after receiving a dose of artemether/lumefantrine, another full dose should be administered as a replacement.1 If the repeat dose is vomited, the patient should be given an alternative antimalarial agent.1
Dosage of artemether/lumefantrine is expressed as the number of tablets of the fixed combination containing 20 mg of artemether and 120 mg of lumefantrine.1
Treatment of Uncomplicated Malaria
For the treatment of acute uncomplicated malaria caused by Plasmodium falciparum , artemether/lumefantrine is given in a regimen that includes a total of 6 doses given over 3 days.1, 144
The recommended dosage of artemether/lumefantrine for the treatment of acute uncomplicated malaria caused by P. falciparum in adults older than 16 years of age weighing 35 kg or more is 4 tablets as an initial dose, followed by 4 tablets 8 hours after the initial dose, and then 4 tablets twice daily (morning and evening) for the next two days (total of 24 tablets given in 6 doses over 3 days).1, 144
Adults weighing less than 35 kg and pediatric patients weighing 5 kg or more should receive a dosage based on weight.1, 144 (See Table 1.)
Weight | Dosage Expressed as Number of Tablets of Artemether/lumefantrine |
|---|---|
5 kg to <15 kg | 1 tablet as initial dose, 1 tablet 8 hours after initial dose, then 1 tablet twice daily (morning and evening) for next 2 days (total of 6 tablets given in 6 doses over 3 days) |
15 kg to <25 kg | 2 tablets as initial dose, 2 tablets 8 hours after initial dose, then 2 tablets twice daily (morning and evening) for next 2 days (total of 12 tablets given in 6 doses over 3 days) |
25 kg to <35 kg | 3 tablets as initial dose, 3 tablets 8 hours after initial dose, then 3 tablets twice daily (morning and evening) for next 2 days (total of 18 tablets given in 6 doses over 3 days) |
≥35 kg | 4 tablets as initial dose, 4 tablets 8 hours after initial dose, then 4 tablets twice daily (morning and evening) for next 2 days (total of 24 tablets given in 6 doses over 3 days) |
For the treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax † in adults or pediatric patients, the US Centers for Disease Control and Prevention (CDC) and other experts recommend the same dosage of artemether/lumefantrine used for treatment of uncomplicated P. falciparum malaria.134, 144 Because artemether/lumefantrine cannot prevent relapse of P. vivax malaria, a 14-day regimen of primaquine phosphate is indicated in conjunction with artemether/lumefantrine to provide a radical cure.134, 143, 144
Presumptive Self-treatment of Malaria
If artemether/lumefantrine is used for presumptive self-treatment of malaria† in adult travelers weighing 35 kg or more, the CDC recommends 4 tablets as an initial dose, followed by 4 tablets 8 hours after the initial dose, and then 4 tablets twice daily (morning and evening) for the next two days (total of 24 tablets given in 6 doses over 3 days).115
For presumptive self-treatment of malaria† in pediatric travelers, the CDC recommends the same weight-based dosage regimen recommended for the treatment of uncomplicated P. falciparum malaria (see Table 1).115
Travelers should be advised to keep an amount of artemether/lumefantrine sufficient for presumptive self-treatment in their possession during travel and to take it promptly in the event of a febrile illness if professional medical care is not readily available.115, 134 Presumptive self-treatment of a possible malarial infection is only a temporary measure; it is imperative that a professional medical evaluation be obtained as soon as possible.115
Dosage adjustment is not needed in patients with mild to moderate hepatic impairment;1 artemether/lumefantrine should be used with caution in patients with severe hepatic impairment.1 (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
Dosage adjustment is not needed in patients with mild to moderate renal impairment;1 artemether/lumefantrine should be used with caution in patients with severe renal impairment.1 (See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
Artemether/lumefantrine is contraindicated in individuals with known hypersensitivity to artemether, lumefantrine, or any ingredient in the formulation.1
Concomitant use of artemether/lumefantrine and drugs that are potent inducers of cytochrome P-450 (CYP) isoenzyme 3A4 (e.g., rifampin, carbamazepine, phenytoin, St. John's wort [ Hypericum perforatum ]) is contraindicated because such use can result in decreased concentrations of artemether and/or lumefantrine and may be associated with loss of antimalarial efficacy.1 (See Drug Interactions.)
Prolongation of the QT Interval
Artemether/lumefantrine is associated with prolongation of the QT interval.1 In clinical trials in adults, increases in QTcF of more than 60 msec from baseline were observed in over 6% of patients; QTcF exceeded 500 msec in 0.3% of patients (3 patients).1 In clinical trials in pediatric patients, increases in QTcF of more than 60 msec from baseline were observed in over 5% of patients; no patient had a QTcF exceeding 500 msec.1
Artemether/lumefantrine should not be used in patients with congenital long QT syndrome, clinical conditions known to prolong the QTc interval (e.g., symptomatic cardiac arrhythmias, clinically important bradycardia, severe cardiac disease), family history of congenital long QT syndrome or sudden death, or electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia).1
In addition, artemether/lumefantrine should not be used in patients receiving other drugs known to cause QT interval prolongation, including class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), class III antiarrhythmic agents (e.g., amiodarone, sotalol), antipsychotics (e.g., pimozide, ziprasidone), antidepressants, certain antimalarials (e.g., quinine, quinidine, halofantrine [not commercially available in the US]), and certain other anti-infectives (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents) or in patients receiving drugs that are metabolized by cytochrome P-450 (CYP) isoenzyme 2D6 (CYP2D6) and are known to have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine).1 If concomitant use of artemether/lumefantrine and other drugs that prolong the QT interval is considered medically necessary, ECGs should be monitored.1 (See Drug Interactions.)
Concomitant or sequential use of artemether/lumefantrine with some other drugs is not recommended or requires particular caution (e.g., other antimalarials, certain antiretroviral agents).1 (See Drug Interactions.)
Patients who are unable to eat while receiving artemether/lumefantrine may be at increased risk of recrudescence and treatment failure since food is needed to enhance absorption of the antimalarial; these individuals should be closely monitored.1
Artemether/lumefantrine should not be used for retreatment in patients who had recrudescence of malaria after treatment with the drug.1 Alternative antimalarial therapy should be used.1
Selection and Use of Antimalarials
Oral antimalarials, including artemether/lumefantrine, should not be used for initial treatment of severe or complicated malaria.1, 143 In the event of life-threatening, serious, or overwhelming malaria, aggressive treatment with a parenteral antimalarial regimen is necessary.143, 144
Because artemether/lumefantrine is active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), primaquine is indicated to provide a radical cure (i.e., eradication of hypnozoites that remain dormant in the liver) if artemether/lumefantrine is used for the treatment of P. vivax or P. ovale malaria†.1, 143, 144
Category C.1 (See Users Guide)
The manufacturer states that efficacy of artemether/lumefantrine for the treatment of acute uncomplicated malaria has not been established in pregnant women, and the drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.1
The US Centers for Disease Control and Prevention (CDC) states that use of artemether/lumefantrine in pregnant women can be considered for treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum when other treatment options are not available or not tolerated and if potential benefits outweigh risks.143
Safety data from approximately 500 pregnant women who received artemether/lumefantrine (about one-third received the drug during the first trimester) and published data from over 1000 pregnant women who were exposed to artemisinin derivatives did not show an increase in adverse pregnancy outcomes or teratogenic effects compared with background rate.1
It is not known whether artemether or lumefantrine is distributed into human milk;1 animal data suggest that both drugs are distributed into milk.1
Artemether/lumefantrine should be used with caution in nursing women and the benefits of breastfeeding to the mother and infant should be weighed against potential risks to the infant.1
Safety and efficacy of artemether/lumefantrine have not been established in children weighing less than 5 kg.1
Studies evaluating safety and efficacy of the drug included children 2 months of age or older weighing at least 5 kg;1 nonimmune children (children residing in nonendemic countries) were not included in these studies.1
Clinical studies did not include sufficient numbers of adults 65 years of age or older to determine whether response differs from younger adults.1
The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or drug therapy observed in geriatric individuals should be considered.1
Pharmacokinetics of artemether/lumefantrine have not been specifically studied in patients with hepatic impairment;1 safety and efficacy have not been evaluated in those with severe hepatic impairment.1
Dosage adjustment is not needed in patients with mild to moderate hepatic impairment.1
Artemether/lumefantrine should be used with caution in patients with severe hepatic impairment.1
Pharmacokinetics of artemether/lumefantrine have not been specifically studied in patients with renal impairment;1 safety and efficacy have not been evaluated in those with severe renal impairment.1
Dosage adjustment is not needed in patients with mild to moderate renal impairment.1
Artemether/lumefantrine should be used with caution in patients with severe renal impairment.1
Adults: Headache, anorexia, dizziness, asthenia, arthralgia, and myalgia.1
Children: Pyrexia, cough, vomiting, anorexia, and headache.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Artemether is metabolized predominantly by the cytochrome P-450 (CYP) 3A4/5 isoenzyme and, to a lesser extent, by CYP isoenzymes 2B6, 2C9, and 2C19.1 Artemether may be a weak inducer of CYP isoenzymes 2C19, 2B6, and 3A4.1 Artemether does not inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.1
Lumefantrine is metabolized principally by CYP3A4.1 Lumefantrine inhibits CYP2D6.1
Potential pharmacokinetic interactions with drugs metabolized by CYP3A4 (decreased plasma concentrations of the drug metabolized by CYP3A4).1
Potential pharmacokinetic interactions with drugs that inhibit or induce CYP3A4 (altered metabolism of artemether and/or lumefantrine).1
Potential pharmacokinetic interactions with drugs metabolized by CYP2D6 (increased plasma concentrations of the CYP2D6 substrate).1 Concomitant use of artemether and lumefantrine (artemether/lumefantrine) and CYP2D6 substrates that are known to have cardiac effects should be avoided (e.g., flecainide, imipramine, amitriptyline, clomipramine).1 (See Drugs that Prolong the QT Interval.)
Drugs that Prolong the QT Interval
Because artemether/lumefantrine prolongs the QT interval, an additive effect on the QT interval might occur if the fixed combination is administered with other agents that prolong the QT interval.1
Because of potential additive effects on the QT interval, artemether/lumefantrine should be avoided in patients receiving other drugs known to cause QT prolongation, including class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), class III antiarrhythmic agents (e.g., amiodarone, sotalol), antipsychotics (e.g., pimozide, ziprasidone), antidepressants, and certain anti-infectives (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents).1
Since many drugs that are metabolized by CYP2D6 can prolong the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine), concomitant use of artemether/lumefantrine and these drugs should be avoided.1
Concomitant or sequential use of artemether/lumefantrine and some other antimalarials (e.g., quinine, quinidine, halofantrine [not commercially available in the US]) should be avoided or requires caution because of potential additive effects on the QT interval.1 (See Drug Interactions: Antimalarial Agents.)
If concomitant use of artemether/lumefantrine and other drugs that prolong the QT interval is considered medically necessary, ECGs should be monitored.1
Concomitant use of artemether/lumefantrine and carbamazepine or phenytoin is contraindicated since concentrations of artemether and/or lumefantrine may be decreased resulting in loss of antimalarial efficacy.1
Concomitant use of ketoconazole and artemether/lumefantrine increases peak plasma concentrations and area under the plasma concentration-time curve (AUC) of artemether, the active metabolite of artemether (dihydroartemisinin; DHA), and lumefantrine.1, 12
Although adjustment of artemether/lumefantrine dosage is not necessary if ketoconazole is used concomitantly,1, 12 ketoconazole and artemether/lumefantrine should be used concomitantly with caution because of the potential for increased lumefantrine concentrations and increased risk of QT prolongation.1
Because safety data are limited, the manufacturer states that artemether/lumefantrine should not be used concurrently with other antimalarial agents unless there are no other treatment options.1
Administration of artemether/lumefantrine 12 hours after mefloquine in healthy adults decreased the peak plasma concentration and AUC of lumefantrine compared with administration of artemether/lumefantrine alone;1, 146 the pharmacokinetics of artemether and mefloquine were not affected.1, 146 Because this pharmacokinetic interaction may occur as the result of lower absorption of lumefantrine secondary to a mefloquine-induced decrease in bile production,1 patients who receive artemether/lumefantrine shortly after mefloquine should be monitored for decreased efficacy and encouraged to take artemether/lumefantrine with food.1
Because of the potential for additive effects on the QT interval and the long elimination half-life of lumefantrine (3-6 days),1, 13 caution is advised and ECG should be monitored if use of quinine or quinidine is considered medically necessary after artemether/lumefantrine.1
A clinically important pharmacokinetic interaction with quinine is unlikely.1, 13
Because of the potential for additive effects on the QT interval and the long elimination half-life of lumefantrine (3-6 days), one month should elapse between administration of halofantrine (not commercially available in the US) and artemether/lumefantrine and vice versa.1
Concomitant use of rifampin (600 mg daily) and artemether/lumefantrine (6-dose regimen given over 3 days) decreased the AUC of artemether, DHA, and lumefantrine by 89, 85, and 68%, respectively.1
Concomitant use of rifampin and artemether/lumefantrine is contraindicated.1
Artemether/lumefantrine should be used with caution in patients receiving antiretroviral agents that have variable effects on CYP3A4, including human immunodeficiency virus (HIV) protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), because decreased artemether, DHA, and/or lumefantrine concentrations may result in decreased antimalarial efficacy and increased lumefantrine concentrations may increase the risk of QT prolongation.1
Concomitant use of ritonavir-boosted darunavir (600 mg of darunavir and 100 mg of ritonavir twice daily for 21 days) and artemether/lumefantrine (6-dose regimen given over 3 days) in healthy individuals decreased the AUC of artemether and DHA by 16-18% and increased the AUC of lumefantrine approximately threefold; the AUCs of darunavir and ritonavir were not affected.14
Concomitant use of lopinavir/ritonavir (400 mg/100 mg twice daily for 26 days) and artemether/lumefantrine (6-dose regimen given over 3 days) in healthy individuals decreased the AUC of artemether and DHA by approximately 40% and increased the AUC of lumefantrine approximately twofold; the AUC of lopinavir was not affected.1, 9
Nonnucleoside Reverse Transcriptase Inhibitors
Concomitant use of efavirenz (600 mg once daily for 26 days) and artemether/lumefantrine (6-dose regimen given over 3 days) in healthy individuals decreased the AUC of artemether, DHA, and lumefantrine by approximately 50, 45, and 20%, respectively, but did not affect the AUC of efavirenz.1, 15
Concomitant use of etravirine (200 mg twice daily for 21 days) and artemether/lumefantrine (6-dose regimen given over 3 days) in healthy individuals decreased the AUC of artemether, DHA, and lumefantrine by 38, 15, and 13%, respectively; the AUC of etravirine was not affected.14
Grapefruit juice should be avoided in patients receiving artemether/lumefantrine because it is an inhibitor of CYP3A4 and may increase artemether and/or lumefantrine concentrations and potentiate QT prolongation.1
Although artemether/lumefantrine does not induce metabolism of ethinyl estradiol or levonorgestrel in vitro, artemether has been reported to be a weak inducer of CYP isoenzymes 2C19, 2B6, and 3A and potentially could reduce effectiveness of hormonal contraceptives.1 Therefore, patients using oral, transdermal, or other systemic hormonal contraceptives should be advised to use additional nonhormonal methods of contraception.1
Artemether and lumefantrine (artemether/lumefantrine) is a fixed combination of 2 antimalarial agents.1 Artemether is an artemisinin-derivative antimalarial1, 161 and lumefantrine is an aryl aminoalcohol antimalarial.161 Both drugs are blood schizonticidal agents active against the erythrocytic stages of Plasmodium .1
Artemether is rapidly metabolized to an active metabolite (dihydroartemisinin; DHA).1 The antimalarial activity of artemether and DHA has been attributed to the endoperoxide moiety.1 The exact mechanism by which lumefantrine exerts its antimalarial effect is not well defined.1 Available data suggest lumefantrine inhibits the formation of β-hematin by forming a complex with hemin.1 Both artemether and lumefantrine were shown to inhibit nucleic acid and protein synthesis.1
Artemether has a rapid onset of action and the drug and its metabolite have elimination half-lives of approximately 2 hours.1, 3, 6 Lumefantrine has a longer elimination half-life (3-6 days).1, 3, 6 The rationale behind the fixed-combination preparation is that the artemisinin derivative (artemether) provides rapid resolution of symptoms by reducing the number of malaria parasites and then lumefantrine clears any residual parasites.3, 6, 161 In addition, use of artemisinin-based combinations may delay or prevent emergence of resistance.161 Although the clinical importance is not known, P. falciparum with decreased susceptibility to artemether or lumefantrine can be selected in vitro or in vivo.1
Following oral administration of artemether/lumefantrine, artemether is rapidly absorbed and peak plasma concentrations are attained within about 2 hours.1 However, lumefantrine is highly lipophilic and absorption is delayed for up to 2 hours and peak plasma concentrations of the drug are attained about 6-8 hours after the dose.1 Food enhances absorption of both drugs.1 Administration of an artemether/lumefantrine tablet after a high-fat meal increases the relative bioavailability of artemether up to threefold and increases the relative bioavailability of lumefantrine sixteenfold compared with administration under fasting conditions.1
Importance of taking each dose of artemether and lumefantrine (artemether/lumefantrine) with food.1
Advise patients that individuals with acute malaria are frequently averse to food; encourage them to resume normal eating as soon as food can be tolerated since this improves absorption of the drug.1
Advise patients to repeat a dose if vomiting occurs within 1-2 hours of ingestion and to contact their clinicians if they also vomit after the repeat dose.1
Advise patients that artemether/lumefantrine can cause hypersensitivity reactions.1 Importance of discontinuing the drug and contacting their clinicians if rash, hives, rapid heartbeat, difficulty swallowing or breathing, swelling of lips, tongue, or face, tightness of throat, or hoarseness occurs.1
Importance of informing clinicians of any personal or family history of QT interval or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia.1
Advise patients to inform their clinicians if they are taking any other medications that prolong the QT interval, including class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), class III antiarrhythmic agents (e.g., amiodarone, sotalol), antipsychotics (e.g., pimozide, ziprasidone), antidepressants, or certain anti-infectives (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents).1
Importance of informing clinician if any symptoms of QT interval prolongation, including prolonged heart palpitations or loss of consciousness occur.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise patients that artemether/lumefantrine may decrease effectiveness of oral, transdermal, or other systemic hormonal contraceptives and that additional nonhormonal methods of contraception should be used.1
Importance of informing patients of other precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
1. Novartis Pharmaceutics Corporation. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2013 Apr.
3. Omari AA, Gamble C, Garner P. Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria. Cochrane Database Syst Rev . 2005; :CD005564.
4. Vugt MV, Wilairatana P, Gemperli B et al. Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg . 1999; 60:936-42. [PubMed 10403324]
5. van Vugt M, Looareesuwan S, Wilairatana P et al. Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg . 2000 Sep-Oct; 94:545-8.
6. Lefèvre G, Looareesuwan S, Treeprasertsuk S et al. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg . 2001 May-Jun; 64:247-56.
7. Hatz C, Soto J, Nothdurft HD et al. Treatment of acute uncomplicated falciparum malaria with artemether-lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study. Am J Trop Med Hyg . 2008; 78:241-7. [PubMed 18256423]
8. Falade C, Makanga M, Premji Z et al. Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg . 2005; 99:459-67. [PubMed 15837358]
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