Артеметер люмефантрин инструкция по применению

Общее название: артеметер и люмефантрин (ar TEM e ther и LOO me FAN treen)
Именамарок:Coartem

Coartem содержит комбинацию артеметер и люмефантрин. Артеметер и люмефантрин являются противомалярийными лекарствами, которые мешают росту паразитов в эритроцитах человеческого тела. Малярия вызвана паразитами, которые проникают в организм через укус москита. Малярия распространена в таких областях, как Африка, Южная Америка и Южная Азия.

Coartem используется для лечения нестрогой малярии .

Coartem используется только для лечения малярии. Не используйте это лекарство для предотвращения малярии.

Серьезные взаимодействия с лекарственными средствами могут возникать, когда определенные лекарства используются вместе. Расскажите своему врачу обо всех ваших текущих лекарствах и о том, что вы начинаете или прекращаете использовать, особенно карбамазепин, фенитоин, рифампин или зверобой.

Слайд-шоу Это Buggin ‘Me! Как безопасно использовать репеллент для насекомых

Вы не должны использовать Coartem, если у вас аллергия на артеметер или люмефантрин.

Некоторые лекарства могут взаимодействовать с артеметом и люмефантрином и не должны использоваться одновременно. Вашему врачу может потребоваться изменить ваш план лечения, если вы используете любой из следующих препаратов:

• рифампицин;

• Зверобой; или

• Судорожная медицина — карбамазепин, фенитоин.

Чтобы убедиться, что Coartem безопасен для вас, сообщите своему врачу, если у вас есть:

• болезнь сердца;

• Личная или семейная история длительного синдрома QT;

• Заболевания печени или почек;

• Низкие уровни калия или магния в крови.

Расскажите своему врачу обо всех других противомалярийных препаратах, которые вы использовали недавно.

Неизвестно, причинит ли Коартем вред нерожденному ребенку. Расскажите своему врачу, если вы беременны или планируете забеременеть.

Используйте барьерную форму контроля рождаемости (презерватив или диафрагму со спермицидом). Гормональная контрацепция (противозачаточные таблетки, инъекции, имплантаты, пятна для кожи и вагинальные кольца) может быть недостаточно эффективной для предотвращения беременности во время вашего лечения.

Неизвестно, переходит ли артеметер и люмефантрин в грудное молоко или может повлиять на грудного ребенка. Расскажите своему врачу, если вы кормите грудью.

Coartem не следует давать ребенку весом менее 11 фунтов.

Возьмите Coartem точно, как предписано вашим доктором. Следуйте всем указаниям на этикетке рецепта. Не принимайте это лекарство в больших или меньших количествах или дольше, чем рекомендуется.

Возьмите Coartem с пищей, молоком, пудингом, овсяной мукой или бульоном. Таблетку можно измельчать и смешивать с 1 или 2 чайными ложками воды для облегчения глотания. Вы также можете смешать дробленную таблетку с детской смесью при предоставлении этого лекарства ребенку. Начните есть как можно скорее, чтобы помочь вашему телу лучше впитывать лекарство.

Если вы рвёте в течение 1 часа после приема этого лекарства, сделайте еще одну дозу. Если ваша рвота продолжается или вы не можете есть, позвоните своему врачу.

Coartem обычно дают в общей сложности 6 доз в течение 3 дней. Тщательно следуйте инструкциям своего врача о том, сколько таблеток принимать на дозу. Дозированные дозы основаны на весе и возрасте. Обычные дозы следующие, если только ваш врач не говорит вам об обратном.

Для людей старше 16 лет, которые весит не менее 77 фунтов:

• Принимать четыре (4) таблетки в качестве начальной дозы.

• Возьмите еще 4 таблетки через 8 часов.

• Возьмите 4 таблетки утром и 4 таблетки вечером в течение следующих 2 дней.

Для детей младше 16 лет, которые весят от 55 до 77 фунтов:

• Возьмите три (3) таблетки в качестве начальной дозы.

• Возьмите еще 3 таблетки через 8 часов.

• Возьмите 3 таблетки утром и 3 таблетки вечером в течение следующих 2 дней.

Для детей младше 16 лет, которые весят от 33 до 55 фунтов:

• Принимать две (2) таблетки в качестве начальной дозы.

• Возьмите еще 2 таблетки через 8 часов.

• Возьмите 2 таблетки утром и 2 таблетки вечером в течение следующих 2 дней.

Для детей младше 16 лет, которые весят от 11 до 33 фунтов:

• Возьмите одну (1) таблетку в качестве начальной дозы.

• Возьмите вторую таблетку через 8 часов.

• Возьмите 1 таблетку утром и 1 таблетку вечером в течение следующих 2 дней.

Никакое лекарство не является эффективным на 100% при лечении малярии. Для достижения наилучших результатов продолжайте использовать Coartem, как указано.

Позвоните своему врачу, если ваши симптомы не улучшится, или если у вас есть лихорадка, озноб, головная боль или боль в мышцах.

Хранить при комнатной температуре вдали от влаги и тепла.

Обычная доза для взрослых коартема для малярии:

Обычная Детская доза Coartem для малярии:

См. Также: Информация дозирования (более подробно)

Читайте так же про препарат Тектурна.

Примите пропущенную дозу, как только вспомните. Пропустите пропущенную дозу, если это почти время для вашей следующей запланированной дозы. Не принимайте дополнительное лекарство, чтобы восполнить пропущенную дозу.

Обратитесь за неотложной медицинской помощью или позвоните в справочную строку Poison по телефону 1-800-222-1222.

Читайте так же про препарат Epclusa.

Избегайте принимать другие лекарства против малярии, если только ваш врач не сказал вам.

Грейпфрут и грейпфрутовый сок могут взаимодействовать с артеметом и люмефантрином и приводить к нежелательным побочным эффектам. Избегайте использования продуктов грейпфрута, принимая Coartem.

Получите экстренную медицинскую помощь, если у вас есть признаки аллергической реакции на Coartem : ульи; Быстрый сердечный ритм; Затрудненное дыхание; Отек лица, губ, языка или горла.

Позвоните своему врачу сразу, если у вас есть серьезные побочные эффекты, такие как:

• Ухудшение симптомов малярии;

• Сильная рвота, потеря аппетита или неспособность есть;

• Быстрое или стучащее сердцебиение;

• Легкомысленное чувство, как вы могли бы исчезнуть; или

• Первый признак любой кожной сыпи, какой бы мягкой она ни была.

Позвоните своему врачу, если у вас развилась лихорадка, озноб, боли в теле, сильная головная боль или симптомы гриппа после того, как вы закончили принимать все ваши дозы Coartem.

Общие побочные эффекты Coartem могут включать:

• Головная боль, головокружение;

• Лихорадка, озноб, кашель, чувство слабости или усталости;

• Жесткость или боль в мышцах и суставах;

• рвота; или

• потеря аппетита.

Это не полный список побочных эффектов, и другие могут возникнуть. Спросите у своего доктора о побочных эффектах. Вы можете сообщить о побочных эффектах FDA на уровне 1-800-FDA-1088.

См. Также: Побочные эффекты (более подробно)

Многие препараты могут взаимодействовать с артеметом и люмефантрином. Здесь перечислены не все возможные взаимодействия. Расскажите своему врачу обо всех ваших текущих лекарствах и о том, что вы начинаете или прекращаете использовать, особенно:

• Другие противомалярийные препараты;

• Антибиотики или лекарства для лечения туберкулеза;

• Антидепрессант;

• Антипсихотические препараты;

• Противозачаточные таблетки или заместительная гормональная терапия;

• Лечение сердечного ритма;

• Противовирусная медицина для лечения ВИЧ или СПИДа; или

• Захват лекарства или медицина для нервной боли в вашем лице.

Этот список не является полным, и многие другие лекарства могут взаимодействовать с артеметером и люмефантрином. Это включает в себя рецептурные и внебиржевые лекарства, витамины и растительные продукты. Дайте список всех ваших лекарств любому поставщику медицинских услуг, который вас лечит.

• Ваш фармацевт может предоставить дополнительную информацию о Coartem.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Overview

Artemether/lumefantrine is an antimalarial that is FDA approved for the treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above.. Common adverse reactions include anorexia, dizziness, arthralgia and myalgia, pyrexia (adults and children) and cough (children).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Artemether and lumefantrine are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above. Artemether and lumefantrine Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported.

• Dosage:

• Tablets should be taken with food
• A 3-day treatment schedule with a total of 6 doses
• 4 tablets as a single initial dose, 4 tablets again after 8 hours and then 4 tablets twice daily (morning and evening) for the following two days (total course of 24 tablets).

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Artemether/lumefantrine in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Artemether/lumefantrine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Artemether and lumefantrine are indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum in patients of 5 kg bodyweight and above. Artemether and lumefantrine Tablets have been shown to be effective in geographical regions where resistance to chloroquine has been reported.

• Dosage:

• Tablets should be taken with food
• 5 kg to less than 15 kg bodyweight: One tablet as an initial dose, 1 tablet again after 8 hours and then 1 tablet twice daily (morning and evening) for the following two days (total course of 6 tablets).
• 15 kg to less than 25 kg bodyweight: Two tablets as an initial dose, 2 tablets again after 8 hours and then 2 tablets twice daily (morning and evening) for the following two days (total course of 12 tablets).
• 25 kg to less than 35 kg bodyweight: Three tablets as an initial dose, 3 tablets again after 8 hours and then 3 tablets twice daily (morning and evening) for the following two days (total course of 18 tablets).
• 35 kg bodyweight and above: Four tablets as a single initial dose, 4 tablets again after 8 hours and then 4 tablets twice daily (morning and evening) for the following two days (total course of 24 tablets).

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Artemether/lumefantrine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Artemether/lumefantrine in pediatric patients.

Contraindications

Hypersensitivity

Known hypersensitivity to artemether, lumefantrine, or to any of the excipients of Artemether and lumefantrine Tablets.

Strong CYP3A4 Inducers

Co-administration of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St. John’s wort with Artemether and lumefantrine Tablets can result in decreased concentrations of artemether and/or lumefantrine and loss of antimalarial efficacy.

Warnings

Prolongation of the QT Interval

Some antimalarials (e.g., halofantrine, quinine, quinidine) including Artemether and lumefantrine Tablets have been associated with QT interval prolongation on the electrocardiogram.

Artemether and lumefantrine Tablets should be avoided in patients:

• with congenital prolongation of the QT interval (e.g., long QT syndrome) or any other clinical condition known to prolong the QTc interval such as patients with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
• with a family history of congenital prolongation of the QT interval or sudden death.
• with known disturbances of electrolyte balance, e.g., hypokalemia or hypomagnesemia.

receiving other medications that prolong the QT interval, such as class IA (quinidine, procainamide, disopyramide), or class III (amiodarone, sotalol) antiarrhythmic agents; antipsychotics (pimozide, ziprasidone); antidepressants; certain antibiotics (macrolide antibiotics, fluoroquinolone antibiotics, imidazole, and triazole antifungal agents).

• receiving medications that are metabolized by the cytochrome enzyme CYP2D6 which also have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine).

Use of QT Prolonging Drugs and Other Antimalarials

Halofantrine and Artemether and lumefantrine Tablets should not be administered within one month of each other due to the long elimination half-life of lumefantrine (3-6 days) and potential additive effects on the QT interval.

Antimalarials should not be given concomitantly with Artemether and lumefantrine Tablets, unless there is no other treatment option, due to limited safety data.

Drugs that prolong the QT interval, including antimalarials such as quinine and quinidine, should be used cautiously following Artemether and lumefantrine Tablets, due to the long elimination half-life of lumefantrine (3-6 days) and the potential for additive effects on the QT interval; ECG monitoring is advised if use of drugs that prolong the QT interval is medically required.

If mefloquine is administered immediately prior to Artemether and lumefantrine Tablets there may be a decreased exposure to lumefantrine, possibly due to a mefloquine-induced decrease in bile production. Therefore, patients should be monitored for decreased efficacy and food consumption should be encouraged while taking Artemether and lumefantrine Tablets.

Drug Interactions with CYP3A4

When Artemether and lumefantrine Tablets are co-administered with substrates of CYP3A4 it may result in decreased concentrations of the substrate and potential loss of substrate efficacy. When Artemether and lumefantrine Tablets are co-administered with an inhibitor of CYP3A4, including grapefruit juice it may result in increased concentrations of artemether and/or lumefantrine and potentiate QT prolongation. When Artemether and lumefantrine Tablets are co-administered with inducers of CYP3A4 it may result in decreased concentrations of artemether and/or lumefantrine and loss of antimalarial efficacy.

Drugs that have a mixed effect on CYP3A4, especially antiretroviral drugs such as HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, and those that have an effect on the QT interval should be used with caution in patients taking Artemether and lumefantrine Tablets.

Artemether and lumefantrine Tablets may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control.

Drug Interactions with CYP2D6

Administration of Artemether and lumefantrine Tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the co-administered drug and increase the risk of adverse effects. Many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with Artemether and lumefantrine Tablets due to the potential additive effect on the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine).

Recrudescence

Food enhances absorption of artemether and lumefantrine following administration of Artemether and lumefantrine Tablets. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be greater.

In the event of recrudescent P. falciparum infection after treatment with Artemether and lumefantrine Tablets, patients should be treated with a different antimalarial drug.

Hepatic and Renal Impairment

Artemether and lumefantrine Tablets have not been studied for efficacy and safety in patients with severe hepatic and/or renal impairment.

Plasmodium vivax Infection

Artemether and lumefantrine Tablets have been shown in limited data (43 patients) to be effective in treating the erythrocytic stage of P. vivax infection. However, relapsing malaria caused by P. vivax requires additional treatment with other antimalarial agents to achieve radical cure i.e., eradicate any hypnozoites forms that may remain dormant in the liver.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice.

The data described below reflect exposure to a 6-dose regimen of Artemether and lumefantrine Tablets in 1,979 patients including 647 adults (older than 16 years) and 1,332 children (16 years and younger). For the 6-dose regimen, Artemether and lumefantrine Tablets was studied in active-controlled (366 patients) and non-controlled, open-label trials (1,613 patients). The 6-dose Artemether and lumefantrine Tablets population was patients with malaria between ages 2 months and 71 years: 67% (1,332) were 16 years and younger and 33% (647) were older than 16 years. Males represented 73% and 53% of the adult and pediatric populations, respectively. The majority of adult patients were enrolled in studies in Thailand, while the majority of pediatric patients were enrolled in Africa.

Tables 1 and 2 show the most frequently reported adverse reactions (≥3%) in adults and children respectively who received the 6-dose regimen of Artemether and lumefantrine Tablets. Adverse reactions collected in clinical trials included signs and symptoms at baseline but only treatment emergent adverse events, defined as events that appeared or worsened after the start of treatment, are presented below. In adults, the most frequently reported adverse reactions were headache, anorexia, dizziness, and asthenia. In children, the adverse reactions were pyrexia, cough, vomiting, anorexia, and headache. Most adverse reactions were mild, did not lead to discontinuation of study medication, and resolved.

In limited comparative studies, the adverse reaction profile of Artemether and lumefantrine Tablets appeared similar to that of another antimalarial regimen.

Discontinuation of Artemether and lumefantrine Tablets due to adverse drug reactions occurred in 1.1% of patients treated with the 6-dose regimen overall: 0.2% (1/647) in adults and 1.6% (21/1,332) in children.

Clinically significant adverse reactions reported in adults and/or children treated with the 6-dose regimen of Artemether and lumefantrine Tablets which occurred in clinical studies at <3% regardless of causality are listed below:

• Blood and lymphatic system disorders: eosinophilia
• Ear and labyrinth disorders: tinnitus
• Eye disorders: conjunctivitis
• Gastrointestinal disorders: constipation, dyspepsia, dysphagia, peptic ulcer
• General disorders: gait disturbance
• Infections and infestations: abscess, acrodermatitis, bronchitis, ear infection, gastroenteritis, helminthic infection, hookworm infection, impetigo, influenza, lower respiratory tract infection, malaria, nasopharyngitis, oral herpes, pneumonia, subcutaneous abscess, upper respiratory tract infection, urinary tract infection
• Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, hematocrit decreased, lymphocyte morphology abnormal, platelet count decreased, platelet count increased, white blood cell count decreased, white blood cell count increased
• Metabolism and nutrition disorders: hypokalemia
• Musculoskeletal and connective tissue disorders: back pain
• Nervous system disorders: ataxia, clonus, fine motor delay, hyperreflexia, hypoaesthesia, nystagmus, tremor
• Psychiatric disorders: agitation, mood swings
• Renal and urinary disorders: hematuria, proteinuria
• Respiratory, thoracic and mediastinal disorders: asthma, pharyngo-laryngeal pain
• Skin and subcutaneous tissue disorders: urticaria

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Artemether and lumefantrine Tablets. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hypersensitivity reactions including urticaria and angioedema. Serious skin reactions (bullous eruption) have been rarely reported.

Drug Interactions

Rifampin

Oral administration of rifampin, a strong CYP3A4 inducer, with Artemether and lumefantrine Tablets resulted in significant decreases in exposure to artemether, dihydroartemisinin (DHA, metabolite of artemether) and lumefantrine by 89%, 85% and 68%, respectively, when compared to exposure values after Artemether and lumefantrine Tablets alone. Concomitant use of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St. John’s wort is contraindicated with Artemether and lumefantrine Tablets.

Ketoconazole

Concurrent oral administration of ketoconazole, a potent CYP3A4 inhibitor, with a single dose of Artemether and lumefantrine Tablets resulted in a moderate increase in exposure to artemether, DHA, and lumefantrine in a study of 15 healthy subjects. No dose adjustment of Artemether and lumefantrine Tablets is necessary when administered with ketoconazole or other potent CYP3A4 inhibitors. However, due to the potential for increased concentrations of lumefantrine which could lead to QT prolongation, Artemether and lumefantrine Tablets should be used cautiously with drugs that inhibit CYP3A4.

Antiretroviral Drugs

Both artemether and lumefantrine are metabolized by CYP3A4. Antiretroviral drugs, such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors, are known to have variable patterns of inhibition, induction or competition for CYP3A4. Therefore, the effects of antiretroviral drugs on the exposure to artemether, DHA, and lumefantrine are also variable. Artemether and lumefantrine Tablets should be used cautiously in patients on antiretroviral drugs because decreased artemether, DHA, and/or lumefantrine concentrations may result in a decrease of antimalarial efficacy of Artemether and lumefantrine Tablets, and increased lumefantrine concentrations may cause QT prolongation.

Prior Use of Mefloquine

Administration of three doses of mefloquine followed 12 hours later by a 6-dose regimen of Artemether and lumefantrine Tablets in 14 healthy volunteers demonstrated no effect of mefloquine on plasma concentrations of artemether or the artemether/DHA ratio. However, exposure to lumefantrine was reduced, possibly due to lower absorption secondary to a mefloquine-induced decrease in bile production. Patients should be monitored for decreased efficacy and food consumption should be encouraged with administration of Artemether and lumefantrine Tablets.

Hormonal Contraceptives

In vitro, the metabolism of ethinyl estradiol and levonorgestrel was not induced by artemether, DHA, or lumefantrine. However, artemether has been reported to weakly induce, in humans, the activity of CYP2C19, CYP2B6, and CYP3A. Therefore, Artemether and lumefantrine Tablets may potentially reduce the effectiveness of hormonal contraceptives. Patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control.

CYP2D6 Substrates

Lumefantrine inhibits CYP2D6 in vitro. Administration of Artemether and lumefantrine Tablets with drugs that are metabolized by CYP2D6 may significantly increase plasma concentrations of the co-administered drug and increase the risk of adverse effects. Many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with Artemether and lumefantrine Tablets due to the potential additive effect on the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine.

Sequential Use of Quinine

A single dose of intravenous quinine (10 mg/kg bodyweight) concurrent with the final dose of a 6-dose regimen of Artemether and lumefantrine Tablets demonstrated no effect of intravenous quinine on the systemic exposure of DHA or lumefantrine. Quinine exposure was also not altered. Exposure to artemether was decreased. This decrease in artemether exposure is not thought to be clinically significant. However, quinine and other drugs that prolong the QT interval should be used cautiously following treatment with Artemether and lumefantrine Tablets due to the long elimination half-life of lumefantrine and the potential for additive QT effects; ECG monitoring is advised if use of drugs that prolong the QT interval is medically required.

Interaction with Drugs that are Known to Prolong the QT Interval

Artemether and lumefantrine is to be used with caution when co-administered with drugs that may cause prolonged QT interval such as antiarrhythmics of classes IA and III, neuroleptics and antidepressant agents, certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C
Safety data from an observational pregnancy study of approximately 500 pregnant women who were exposed to Artemether and lumefantrine Tablets (including a third of patients who were exposed in the first trimester), and published data of over 1,000 pregnant patients who were exposed to artemisinin derivatives, did not show an increase in adverse pregnancy outcomes or teratogenic effects over background rate.

The efficacy of Artemether and lumefantrine Tablets in the treatment of acute, uncomplicated malaria in pregnant women has not been established.

Artemether and lumefantrine Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnant rats dosed during the period of organogenesis at or higher than a dose of about half the highest clinical dose of 1120 mg artemether-lumefantrine per day (based on body surface area comparisons), showed increases in fetal loss, early resorptions and post implantation loss. No adverse effects were observed in animals dosed at about one-third the highest clinical dose. Similarly, dosing in pregnant rabbits at about three times the clinical dose (based on body surface area comparisons) resulted in abortions, preimplantation loss, post implantation loss and decreases in the number of live fetuses. No adverse reproductive effects were detected in rabbits at two times the clinical dose. Embryo-fetal loss is a significant reproductive toxicity. Other artemisinins are known to be embryotoxic in animals. However, because metabolic profiles in animals and humans are dissimilar, artemether exposures in animals may not be predictive of human exposures. These data cannot rule out an increased risk for early pregnancy loss or fetal defects in humans.

Pregnancy Category (AUS): D
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Artemether/lumefantrine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Artemether/lumefantrine during labor and delivery.

Nursing Mothers

It is not known whether artemether or lumefantrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Artemether and lumefantrine Tablets are administered to a nursing woman. Animal data suggest both artemether and lumefantrine are excreted into breast milk. The benefits of breastfeeding to mother and infant should be weighed against potential risk from infant exposure to artemether and lumefantrine through breast milk.

Pediatric Use

The safety and effectiveness of Artemether and lumefantrine Tablets have been established for the treatment of acute, uncomplicated malaria in studies involving pediatric patients weighing 5 kg or more. The safety and efficacy have not been established in pediatric patients who weigh less than 5 kg. Children from non-endemic countries were not included in clinical trials.

Geriatic Use

Clinical studies of Artemether and lumefantrine Tablets did not include sufficient numbers of subjects aged 65 years and over to determine they respond differently from younger subjects. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing Artemether and lumefantrine Tablets.

Gender

There is no FDA guidance on the use of Artemether/lumefantrine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Artemether/lumefantrine with respect to specific racial populations.

Renal Impairment

No specific pharmacokinetic studies have been performed in patients with renal impairment. Artemether and lumefantrine Tablets have not been studied for efficacy and safety in patients with severe renal impairment. Based on the pharmacokinetic data in 16 healthy subjects showing no or insignificant renal excretion of lumefantrine, artemether and DHA, no dose adjustment for the use of Artemether and lumefantrine in patients with renal impairment is advised.

Hepatic Impairment

No specific pharmacokinetic studies have been performed in patients with either hepatic or renal impairment. Artemether and lumefantrine Tablets have not been studied for efficacy and safety in patients with severe hepatic impairment. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment

Females of Reproductive Potential and Males

Pregnancy rates were reduced by about one half in female rats dosed for 2 to 4 weeks with the artemether-lumefantrine combination at 1000 mg/kg (about 9 times the clinical dose based on body surface area comparisons). Male rats dosed for 70 days showed increases in abnormal sperm (87% abnormal) and increased testes weights at 30 mg/kg doses (about one third the clinical dose). Higher doses (about 9 times the clinical dose) resulted in decreased sperm motility and 100% abnormal sperm cells.

Immunocompromised Patients

There is no FDA guidance one the use of Artemether/lumefantrine in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral

Monitoring

There is limited information regarding Artemether/lumefantrine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Artemether/lumefantrine and IV administrations.

Overdosage

There is no information on overdoses of Artemether and lumefantrine Tablets higher than the doses recommended for treatment.

In cases of suspected overdosage, symptomatic and supportive therapy, which would include ECG and blood electrolyte monitoring, should be given as appropriate.

Pharmacology

Mechanism of Action

Artemether and lumefantrine Tablets, a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively, is an antimalarial agent. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. The exact mechanism by which lumefantrine, exerts its antimalarial effect is not well defined. Available data suggest lumefantrine inhibits the formation of β-hematin by forming a complex with hemin. Both artemether and lumefantrine were shown to inhibit nucleic acid and protein synthesis.

Structure

It has the empirical formula C16H26O5 with a molecular weight of 298.4, and the following structural formula:

Pharmacodynamics

Effects on the Electrocardiogram

In a healthy adult volunteer parallel group study including a placebo and moxifloxacin control group (n=42 per group), the administration of the 6-dose regimen of Artemether and lumefantrine Tablets was associated with prolongation of QTcF (Fridericia). Following administration of a 6-dose regimen of Artemether and lumefantrine Tablets consisting of 4 tablets per dose (total of 4 tablets of 80 mg artemether/480 mg lumefantrine) taken with food, the maximum mean change from baseline and placebo adjusted QTcF was 7.5 msec (1-sided 95% Upper CI: 11 msec). There was a concentration-dependent increase in QTcF for lumefantrine.

In clinical trials conducted in children, no patient had QTcF >500 msec. Over 5% of patients had an increase in QTcF of over 60 msec.

In clinical trials conducted in adults, QTcF prolongation of >500 msec was reported in 3 (0.3%) of patients. Over 6% of adults had a QTcF increase of over 60 msec from baseline.

Pharmacokinetics

Absorption

Following administration of Artemether and lumefantrine Tablets to healthy volunteers and patients with malaria, artemether is absorbed with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with peak plasma concentrations about 6 to 8 hours after administration. The single dose (4 tablets) pharmacokinetic parameters for artemether, dihydroartemisinin (DHA), an active antimalarial metabolite of artemether, and lumefantrine in adult Caucasian healthy volunteers are given in Table 3. Multiple dose data after the 6-dose regimen of Artemether and lumefantrine Tablets in adult malaria patients are given in Table 4.

Food enhances the absorption of both artemether and lumefantrine. In healthy volunteers, the relative bioavailability of artemether was increased between two- to three-fold, and that of lumefantrine sixteen-fold when Artemether and lumefantrine Tablets were taken after a high-fat meal compared under fasted conditions. Patients should be encouraged to take Artemether and lumefantrine Tablets with a meal as soon as food can be tolerated.

Distribution

Artemether and lumefantrine are both highly bound to human serum proteins in vitro (95.4% and 99.7%, respectively). Dihydroartemisinin is also bound to human serum proteins (47% to 76%). Protein binding to human plasma proteins is linear.

Biotransformation

In human liver microsomes and recombinant CYP450 enzymes, the metabolism of artemether was catalyzed predominantly by CYP3A4/5. Dihydroartemisinin (DHA) is an active metabolite of artemether. The metabolism of artemether was also catalyzed to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. In vitro studies with artemether at therapeutic concentrations revealed no significant inhibition of the metabolic activities of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and CYP4A9/11. In vitro studies with artemether, DHA, and lumefantrine at therapeutic concentrations revealed no significant induction of the metabolic activities of CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, or CYP3A5.

During repeated administration of Artemether and lumefantrine Tablets, systemic exposure of artemether decreased significantly, while concentrations of DHA increased, although not to a statistically significant degree. The artemether/DHA AUC ratio is 1.2 after a single dose and 0.3 after 6 doses given over 3 days. This suggests that there was induction of enzymes responsible for the metabolism of artemether.

In human liver microsomes and in recombinant CYP450 enzymes, lumefantrine was metabolized mainly by CYP3A4 to desbutyl-lumefantrine. The systemic exposure to the metabolite desbutyl-lumefantrine was less than 1% of the exposure to the parent compound. In vitro, lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations.

Caution is recommended when combining Artemether and lumefantrine Tablets with substrates, inhibitors, or inducers of CYP3A4, especially antiretroviral drugs and those that prolong the QT interval (e.g., macrolide antibiotics, pimozide).

Co-administration of Artemether and lumefantrine Tablets with CYP2D6 substrates may result in increased plasma concentrations of the CYP2D6 substrate and increase the risk of adverse reactions. In addition, many of the drugs metabolized by CYP2D6 can prolong the QT interval and should not be administered with Artemether and lumefantrine Tablets due to the potential additive effect on the QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine).

Elimination

Artemether and DHA are cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated more slowly, with an elimination half-life of 3-6 days in healthy volunteers and in patients with falciparum malaria. Demographic characteristics such as sex and weight appear to have no clinically relevant effects on the pharmacokinetics of artemether and lumefantrine.

In 16 healthy volunteers, neither lumefantrine nor artemether was found in the urine after administration of Artemether and lumefantrine, and urinary excretion of DHA amounted to less than 0.01% of the artemether dose.

Nonclinical Toxicology

Activity In Vitro and In Vivo

Artemether and lumefantrine are active against the erythrocytic stages of Plasmodium falciparum.

Drug Resistance

Strains of P. falciparum with a moderate decrease in susceptibility to artemether or lumefantrine alone can be selected in vitro or in vivo, but not maintained in the case of artemether. The clinical relevance of such an effect is not known.

Carcinogenesis

Carcinogenicity studies were not conducted.

Mutagenesis

No evidence of mutagenicity was detected. The artemether: lumefantrine combination was evaluated using the Salmonella and Escherichia/mammalian-microsome mutagenicity test, the gene mutation test with Chinese hamster cells V79, the cytogenetic test on Chinese hamster cells in vitro, and the rat micronucleus test, in vivo.

Animal Toxicology and/or Pharmacology

Neonatal rats (7-21 days old) were more sensitive to the toxic effects of artemether (a component of Artemether and lumefantrine) than older juvenile rats or adults. Mortality and severe clinical signs were observed in neonatal rats at doses which were well tolerated in pups above 22 days old.

Clinical Studies

Treatment of Acute, Uncomplicated P. falciparum Malaria

The efficacy of Artemether and lumefantrine Tablets was evaluated for the treatment of acute, uncomplicated malaria caused by P. falciparum in HIV negative patients in 8 clinical studies. Uncomplicated malaria was defined as symptomatic P. falciparum malaria without signs and symptoms of severe malaria or evidence of vital organ dysfunction. Baseline parasite density ranged from 500/µL — 200,000/µL (0.01% to 4% parasitemia) in the majority of patients. Studies were conducted in partially immune and non-immune adults and children (≥5kg body weight) with uncomplicated malaria in China, Thailand, sub-Saharan Africa, Europe, and South America. Patients who had clinical features of severe malaria, severe cardiac, renal, or hepatic impairment were excluded.

The studies include two 4-dose studies assessing the efficacy of the components of the regimen, a study comparing a 4-dose versus a 6-dose regimen, and 5 additional 6-dose regimen studies.

Artemether and lumefantrine Tablets were administered at 0, 8, 24, and 48 hours in the 4-dose regimen, and at 0, 8, 24, 36, 48, and 60 hours in the 6-dose regimen. Efficacy endpoints consisted of:

• 28 day cure rate, defined as clearance of asexual parasites (the erythrocytic stage) within 7 days without recrudescence by day 28
• parasite clearance time (PCT), defined as time from first dose until first total and continued disappearance of asexual parasite which continues for a further 48 hours
• fever clearance time (FCT), defined as time from first dose until the first time body temperature fell below 37.5°C and remained below 37.5°C for at least a further 48 hours (only for patients with temperature >37.5°C at baseline)

The modified intent to treat (mITT) population includes all patients with malaria diagnosis confirmation who received at least one dose of study drug. Evaluable patients generally are all patients who had a day 7 and a day 28 parasitological assessment or experienced treatment failure by day 28.

Studies 1 and 2

The two studies which assessed the efficacy of Artemether and lumefantrine Tablets (4 doses of 4 tablets of 20 mg artemether/120 mg lumefantrine) compared to each component alone were randomized, double-blind, comparative, single center, conducted in China. The efficacy results (Table 5) support that the combination of artemether and lumefantrine in Artemether and lumefantrine Tablets had a significantly higher 28-day cure rate compared to artemether and had a significantly faster parasite clearance time (PCT) and fever clearance time (FCT) compared to lumefantrine.

Results of 4-dose studies conducted in areas with high resistance such as Thailand during 1995-96 showed lower efficacy results than the above studies. Therefore, Study 3 was conducted.

Study 3

Study 3 was a randomized, double-blind, two-center study conducted in Thailand in adults and children (aged ≥2 years), which compared the 4-dose regimen (administered over 48 hours) of Artemether and lumefantrine Tablets to a 6-dose regimen (administered over 60 hours). Twenty-eight day cure rate in mITT subjects was 81% (96/118) for the Artemether and lumefantrine Tablets 6-dose arm as compared to 71% (85/120) in the 4-dose arm.

Studies 4, 5, 6, 7, and 8

In these studies, Artemether and lumefantrine Tablets were administered as the 6-dose regimen.

In study 4, a total of 150 adults and children aged ≥2 years received Artemether and lumefantrine Tablets. In study 5, a total 164 adults and children ≥12 years received Artemether and lumefantrine Tablets. Both studies were conducted in Thailand.

Study 6 was a study of 165 non-immune adults residing in regions non-endemic for malaria (Europe and Colombia) who contracted acute uncomplicated falciparum malaria when traveling in endemic regions.

Study 7 was conducted in Africa in 310 infants and children aged 2 months to 9 years, weighing 5 kg to 25 kg, with an axillary temperature ≥37.5ºC.

Study 8 was conducted in Africa in 452 infants and children, aged 3 months to 12 years, weighing 5 kg to <35 kg, with fever (≥37.5°C axillary or ≥38°C rectally) or history of fever in the preceding 24 hours.

Results of 28-day cure rate, median parasite clearance time (PCT), and fever clearance time (FCT) for Studies 3 to 8 are reported in Table 6.

In all studies, patients’ signs and symptoms of malaria resolved when parasites were cleared.

In studies conducted in areas with high transmission rates, such as Africa, reappearance of P. falciparum parasites may be due to recrudescence or a new infection.

The efficacy by body weight category for studies 7 and 8 is summarized in Table 7.

The efficacy of Artemether and lumefantrine Tablets for the treatment P. falciparum infections mixed with P. vivax was assessed in a small number of patients. Artemether and lumefantrine Tablets are only active against the erythrocytic phase of P. vivax malaria. Of the 43 patients with mixed infections at baseline, all cleared their parasitemia within 48 hours. However, parasite relapse occurred commonly (14/43; 33%). Relapsing malaria caused by P. vivax requires additional treatment with other antimalarial agents to achieve radical cure i.e., eradicate any hypnozoite forms that may remain dormant in the liver.

How Supplied

• Artemether and lumefantrine 20 mg/120 mg Tablets

• Bottle of 24
• NDC 0078-0568-45

Storage

Store at 25°C (77°F)

Images

Drug Images

{{#ask: Page Name::Artemether/lumefantrine
|?Pill Name
|?Drug Name
|?Pill Ingred
|?Pill Imprint
|?Pill Dosage
|?Pill Color
|?Pill Shape
|?Pill Size (mm)
|?Pill Scoring
|?NDC
|?Drug Author
|format=template
|template=DrugPageImages
|mainlabel=-
|sort=Pill Name
}}

Package and Label Display Panel

{{#ask: Label Page::Artemether/lumefantrine
|?Label Name
|format=template
|template=DrugLabelImages
|mainlabel=-
|sort=Label Page
}}

Patient Counseling Information

Information for Safe Use:

• Instruct patients to take Artemether and lumefantrine Tablets with food. Patients who do not have an adequate intake of food are at risk for recrudescence of malaria.
• Patients with known hypersensitivity to artemether, lumefantrine, or to any of the excipients should not receive Artemether and lumefantrine Tablets.
• Instruct patients to inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia.
• Instruct patients to inform their physician if they are taking any other medications that prolong the QT interval, such as class IA (quinidine, procainamide, disopyramide), or class III (amiodarone, sotalol) antiarrhythmic agents; antipsychotics (pimozide, ziprasidone); antidepressants; certain antibiotics (macrolide antibiotics, fluoroquinolone antibiotics, imidazole, and triazole antifungal agents).
• Instruct patients to notify their physicians if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.
• Instruct patients to avoid medications that are metabolized by the cytochrome enzyme CYP2D6 while receiving Artemether and lumefantrine Tablets since these drugs also have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine).
• Inform patients that based on animal data, Artemether and lumefantrine Tablets administered during pregnancy may result in fetal loss. Fetal defects have been reported when artemisinins are administered to animals.
• Halofantrine and Artemether and lumefantrine Tablets should not be administered within one month of each other due to potential additive effects on the QT interval.
• Antimalarials should not be given concomitantly with Artemether and lumefantrine Tablets, unless there is no other treatment option, due to limited safety data.
• QT prolonging drugs, including quinine and quinidine, should be used cautiously following Artemether and lumefantrine Tablets due to the long elimination half-life of lumefantrine and the potential for additive effects on the QT interval. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required.
• Closely monitor food intake in patients who received mefloquine immediately prior to treatment with Artemether and lumefantrine Tablets.
• Use Artemether and lumefantrine Tablets cautiously in patients receiving other drugs that are substrates, inhibitors or inducers of CYP3A4, including grapefruit juice, especially those that prolong the QT interval or are antiretroviral drugs.
• Co-administration of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St. John’s wort is contraindicated with Artemether and lumefantrine Tablets.

Artemether and lumefantrine Tablets may reduce the effectiveness of hormonal contraceptives. Therefore, patients using oral, transdermal patch, or other systemic hormonal contraceptives should be advised to use an additional non-hormonal method of birth control.

• Inform patients that Artemether and lumefantrine Tablets can cause hypersensitivity reactions. Instruct patients to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.

Precautions with Alcohol

Alcohol-Artemether/lumefantrine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Coartem ^[1]

Look-Alike Drug Names

There is limited information regarding Artemether/lumefantrine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Description and Brand Names

Drug information provided by: Merative, Micromedex®

US Brand Name

1. Coartem

Descriptions

Artemether and lumefantrine combination is used to treat acute, uncomplicated malaria in patients 2 months of age and older who weigh at least 5 kilograms (kg). It may be used to treat malaria infections in areas or regions where it is known that other medicines (eg, chloroquine) may not work.

Artemether and lumefantrine combination belongs to a group of medicines known as antimalarials. It treats malaria, a red blood cell infection transmitted by the bite of a mosquito. However, this medicine is not used to prevent malaria or to treat severe or complicated malaria.

This medicine is available only with your doctor’s prescription.

This product is available in the following dosage forms:

• Tablet

Before Using

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of artemether and lumefantrine combination in children 2 months of age and older weighing 5 kilograms (kg) or more. However, safety and efficacy have not been established in children younger than 2 months of age weighing less than 5 kg.

Geriatric

Appropriate studies on the relationship of age to the effects of artemether and lumefantrine combination have not been performed in the geriatric population. However, geriatric-specific problems that would limit the usefulness of this medication in the elderly are not expected.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Aurothioglucose
• Bepridil
• Carbamazepine
• Cisapride
• Dexamethasone
• Dronedarone
• Enzalutamide
• Fluconazole
• Fosphenytoin
• Ketoconazole
• Levoketoconazole
• Mesoridazine
• Nelfinavir
• Phenytoin
• Pimozide
• Piperaquine
• Posaconazole
• Rifabutin
• Rifampin
• Rifapentine
• Saquinavir
• Sparfloxacin
• St John’s Wort
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adagrasib
• Alfuzosin
• Amiodarone
• Amisulpride
• Amitriptyline
• Amoxapine
• Amprenavir
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Boceprevir
• Buprenorphine
• Buserelin
• Ceritinib
• Chloroquine
• Chlorpromazine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clothiapine
• Clozapine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Desogestrel
• Deutetrabenazine
• Dexmedetomidine
• Dienogest
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Droperidol
• Drospirenone
• Efavirenz
• Encorafenib
• Entrectinib
• Erythromycin
• Escitalopram
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Etravirine
• Fexinidazole
• Fingolimod
• Flecainide
• Fluoxetine
• Formoterol
• Fosamprenavir
• Foscarnet
• Fostemsavir
• Gatifloxacin
• Gemifloxacin
• Gepirone
• Gestodene
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Indinavir
• Inotuzumab Ozogamicin
• Ivabradine
• Ivosidenib
• Lapatinib
• Lefamulin
• Lenvatinib
• Leuprolide
• Levofloxacin
• Levonorgestrel
• Lofexidine
• Lopinavir
• Macimorelin
• Medroxyprogesterone
• Mestranol
• Methadone
• Metronidazole
• Mifepristone
• Mirtazapine
• Mobocertinib
• Moxifloxacin
• Nafarelin
• Nelfinavir
• Nevirapine
• Nilotinib
• Nomegestrol
• Norelgestromin
• Norethindrone
• Norfloxacin
• Norgestimate
• Norgestrel
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Ozanimod
• Pacritinib
• Paliperidone
• Panobinostat
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Phenobarbital
• Pimavanserin
• Pitolisant
• Ponesimod
• Primidone
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Quizartinib
• Ranolazine
• Relugolix
• Ribociclib
• Ritonavir
• Segesterone
• Selpercatinib
• Sertraline
• Sevoflurane
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tipranavir
• Toremifene
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimipramine
• Triptorelin
• Ulipristal
• Vandetanib
• Vardenafil
• Vemurafenib
• Vilanterol
• Vinflunine
• Voclosporin
• Voriconazole
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Mefloquine

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bradycardia (slow heartbeat), severe or
• Heart attack, recent or
• Heart disease, severe or
• Heart rhythm problems (eg, prolonged QT interval, congenital long QT interval), or a history of or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood)—Use is not recommended. May increase the risk of severe heart rhythm problems.

• Decreased food intake during treatment—May increase the chance for this infection to return.

• Kidney disease, severe or
• Liver disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Talk with your doctor if you have any questions.

This medicine should be taken with food or drinks (eg, milk, infant formula, pudding, porridge, or broth). This will help your body absorb the medicine.

If you or your child are unable to swallow the tablet, it may be crushed and mixed with one or two teaspoons of water in a clean container.

Keep using this medicine for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For the treatment of malaria:
    • Adults and children 2 months of age and older weighing 35 kilograms or more—At first, 4 tablets as a single dose, then one dose (4 tablets) after 8 hours. On days 2 and 3, take one dose (4 tablets) two times a day. This 3-day treatment schedule should have a total of 24 tablets in six doses.
    • Children 2 months of age and older weighing 25 kg to less than 35 kg—At first, 3 tablets as a single dose, then one dose (3 tablets) after 8 hours. On days 2 and 3, take one dose (3 tablets) two times a day. This 3-day treatment schedule should have a total of 18 tablets in six doses.
    • Children 2 months of age and older weighing 15 kg to less than 25 kg—At first, 2 tablets as a single dose, then one dose (2 tablets) after 8 hours. On days 2 and 3, take one dose (2 tablets) two times a day. This 3-day treatment schedule should have a total of 12 tablets in six doses.
    • Children 2 months of age and older weighing 5 kg to less than 15 kg—At first, 1 tablet as a single dose, then one dose (1 tablet) after 8 hours. On days 2 and 3, take one dose (1 tablet) two times a day. This 3-day treatment schedule should have a total of 6 tablets in six doses.
    • Children younger than 2 months of age weighing less than 5 kg—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you or your child vomit within 1 to 2 hours of taking this medicine, take another dose. If you vomit the second dose, tell your doctor right away. You may need to use a different medicine to treat your condition.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Store the medicine in the original package with the container tightly closed.

Precautions

It is important that your doctor check your or your child’s progress after treatment. This is to make sure that the infection is cleared up completely, and to allow your doctor to check for any unwanted effects.

If your or your child’s symptoms do not improve within a few days or if they become worse, check with your doctor.

Tell your doctor if you or your child have used other medicines to treat your malaria infection. Using this medicine together with halofantrine (Halfan®), mefloquine (Lariam®), or quinine may increase the chance for more serious side effects.

This medicine can cause changes in heart rhythms, such as a condition called QT prolongation. It may change the way your heart beats and cause fainting or serious side effects in some patients. Call your doctor right away if you or your child have any symptoms of heart rhythm problems, such as fast, pounding, or irregular heartbeats.

Check with your doctor right away if you or your child have flu-like symptoms (such as chills, fever, headache, or muscle pains) again after treatment with this medicine.

This medicine may cause serious allergic reactions. Call your doctor right away if you or your child have a rash, itching, hives, hoarseness, trouble with breathing, trouble with swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

Malaria is spread by the bites of certain kinds of infected female mosquitoes. If you are living in or will be traveling to an area where there is a chance of getting malaria, the following mosquito-control measures will help to prevent infection:

• If possible, avoid going out between dusk and dawn because it is at these times that mosquitoes most commonly bite.
• Wear long-sleeved shirts and long trousers to protect your arms and legs, especially from dusk through dawn when mosquitoes are out.
• Apply insect repellant, preferably one containing DEET, to uncovered areas of the skin from dusk through dawn when mosquitoes are out.
• If possible, sleep in a screened or air-conditioned room or under mosquito netting sprayed with insecticide to avoid being bitten by malaria-carrying mosquitoes.
• Use mosquito coils or sprays to kill mosquitoes in living and sleeping quarters during evening and nighttime hours.

This medicine may decrease the effects of birth control pills or transdermal patches. To avoid an unwanted pregnancy, it is a good idea to use additional contraceptive measures with your pills or patches (eg, condoms, a diaphragm, or a contraceptive foam or jelly) while using this medicine.

Grapefruits and grapefruit juice may increase the effects of artemether and lumefantrine combination by increasing the amount of this medicine in your body. You should not eat grapefruit or drink grapefruit juice while you or your child are taking this medicine.

Do not take other medicines, including prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements, unless they have been discussed with your doctor. Artemether and lumefantrine combination should not be taken with certain other medicines, including carbamazepine (Tegretol®), phenytoin (Dilantin®), rifampin (Rifadin®, Rimactane®), or St. John’s wort.

Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

1. Abdominal or stomach pain
2. chills
3. cough
4. fast, irregular, pounding, or racing heartbeat or pulse
5. fever
6. headache
7. muscle aches
8. pale skin
9. right upper abdominal or stomach pain and fullness
10. sore throat
11. stuffy or runny nose
12. troubled breathing with exertion
13. unusual bleeding or bruising
14. unusual tiredness or weakness

Less common

1. Accumulation of pus
2. acid or sour stomach
3. belching
4. black, tarry stools
5. bladder pain
6. blood in the urine
7. bloody or cloudy urine
8. body aches or pain
9. change in hearing
10. chest pain
11. cloudy urine
12. convulsions
13. cough producing mucus
14. decreased urine
15. diarrhea
16. difficult, burning, or painful urination
17. difficulty with breathing
18. difficulty with swallowing
19. dizziness
20. dry mouth
21. ear congestion
22. ear drainage
23. earache or pain in the ear
24. frequent urge to urinate
25. general feeling of discomfort or illness
26. heartburn
27. increased thirst
28. indigestion
29. joint pain
30. loss of appetite
31. loss of voice
32. lower back or side pain
33. mood changes
34. muscle pain or cramps
35. nasal congestion
36. nausea or vomiting
37. noisy breathing
38. numbness or tingling in the hands, feet, or lips
39. red rash with watery, yellow-colored, or pus filled blisters
40. shivering
41. sneezing
42. sores, ulcers, or white spots on the lips or in the mouth
43. stomach discomfort, upset, or pain
44. sweating
45. swollen glands
46. swollen, red, tender area of infection
47. thick yellow to honey-colored crusts
48. tightness in the chest
49. troubled sleeping

Incidence not known

1. Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

1. Difficulty with moving
2. lack or loss of strength
3. muscle aching or cramping
4. muscle pain or stiffness
5. weight loss

Less common

1. Back pain
2. burning, crawling, itching, numbness, prickling, «pins and needles», or tingling feelings
3. burning, dry, or itching eyes
4. continuing ringing or buzzing or other unexplained noise in the ears
5. difficulty having a bowel movement (stool)
6. discharge or excessive tearing
7. dizziness or lightheadedness
8. feeling of constant movement of self or surroundings
9. hearing loss
10. hives or welts
11. redness of the skin
12. redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
13. sensation of spinning
14. shakiness and unsteady walk
15. shakiness in the legs, arms, hands, or feet
16. trembling or shaking of the hands or feet
17. uncontrolled eye movements
18. unsteadiness, trembling, or other problems with muscle control or coordination

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: Nov. 01, 2023

Original article: https://www.mayoclinic.org/drugs-supplements/artemether-and-lumefantrine-oral-route/proper-use/drg-20072694