Artemether and Lumefantrine

Artemether and lumefantrine (brand name Coartem) is a combination antimalarial medicine used to treat non-severe malaria in adults and children (in patients who weigh at least 11 pounds).

Overview

The combination of artemether and lumefantrine is prescribed for treatment of certain kinds of malaria infections (a serious tropical infection caused by Plasmodium falciparum and spread by female anopheles mosquito). Belonging to a class of medications referred to as antimalarials, artemether and lumefantrine should not be used for malaria prevention.

Artemether and lumefantrine (brand name Coartem) works by killing plasmodium falciparum, the protozoal parasite that causes malaria. Artemether and lumefantrine are the two active ingredients that cure malaria by killing malaria causing pathogens.

As already indicated, malaria is caused by a protozoal parasite Plasmodium, which is transmitted by female anopheles mosquitoes. During a bite, the infected mosquito passes the parasite into the human body, where it lives and reproduces, resulting in the tropical disease known as malaria.

Plasmodium has various stages in its lifecycle within the body. After entering the bloodstream during a bite, it is transported to the liver where it reproduces. It is then released back into the bloodstream where it attacks the red blood cells.

In the red blood cells, Plasmodium digests hemoglobin, the protein within the red blood cell that is responsible for transporting oxygen. Upon attack by Plasmodium, hemoglobin splits into two components – haem and globin. Haem is toxic to plasmodium. Thus, the parasite protects itself by producing a substance that converts the toxic haem to a compound known as haemozoin, which does not affect the parasite.

Artemether and lumefantrine works by interfering with Plasmodium’s ability to convert haem to haemozoin. This results in a rise in the levels of the toxic haem, which destroys the blood stages of plasmodium to stop the infection from progressing.

Coartem tablets are administered orally to treat malaria caused by Plasmodium falciparum (P. falciparum) parasites. However, this medication should not be used in the following circumstances:

  • Treating severe malaria – According to World Health Organization, this is a form of malaria that causes pulmonary oedema, affects the brain or causes kidney failure
  • Treating a patient with a family history of sudden death
  • Treating a patient with a history of irregular heart rhythm
  • Treating patients with diseases or conditions that can trigger irregular heart rhythm, or patients taking other medications that can cause this condition
  • Treating patients with bradycardia (slow heart rate)
  • Treating a patient with a history of heart failures
  • Treating patients with disturbances in blood salt levels (hypokalaemia or hypomagnesaemia)
  • Treating expectant and breastfeeding mothers

What you need to know while taking artemether and lumefantrine

  • Inform all of your healthcare providers that you are taking artemether and lumefantrine. These include your doctors, pharmacists, nurses and dentists
  • Avoid operating machinery, driving or handling tasks that require you to be alert until you establish how this medication affects you
  • To reduce your chances of feeling dizzy and passing out, rise slowly if you have been in a sitting or lying position. Be attentive when going up and down stairs.
  • You may need to have an ECG check-up before starting artemether and lumefantrine and while on the medication. Talk to your doctor about this.
  • Avoid grapefruit as well as grapefruit juice
  • Hormone based birth control medications may not work well during artemether and lumefantrine medication. Therefore, use some other forms of birth control while on this medication.
  • Inform your doctor if you are pregnant or are planning to get pregnant soon before starting this medication. Based on your condition, your doctor will weigh the benefits versus the risks of using artemether and lumefantrine before approving its use during pregnancy.
  • Inform your doctor if you are breastfeeding before taking this medication as studies have shown that the ingredients can be passed on to the baby via breast milk.

Conditions treated by artemether and lumefantrine

  • Non-severe malaria

Type of medicine

  • antimalarials

Side effects of artemether and lumefantrine

Medications and their side effects affect individual patients in different ways. The following are some of the side effects that are associated with artemether and lumefantrine. However, it is important to note that because a side effect has been stated here does not mean that all patients using this medication will experience any or all the side effects.

General side effects

The most frequently reported side effects of artemether and lumefantrine include anorexia, headache, asthenia and dizziness. These side effects are often mild and should not lead to the discontinuation of the medication.

Effects on the nervous system

Nervous system side effects of artemether and lumefantrine include vertigo, headache and dizziness. Other side effects include tinnitus, clonus, ataxia, fine motor delay, hypoesthesia, hyperreflexia, nystagmus and tremors. Some patients also experience ototoxicity (including decreased hearing) and paresthesia.

Gastrointestinal side effects

Gastrointestinal side effects of artemether and lumefantrine include nausea, anorexia, light diarrhea and abdominal pains. Some patients may experience constipation, dysphagia, dyspepsia, and peptic ulcers.

Cardiovascular side effects

Cardiovascular side effects of this medication include QT interval prolongation and palpitations

Hypersensitivity side effects

Some patients may experience hypersensitive reactions while using this medication. These include angioedema and urticaria.

Hematologic side effects

Hematologic side effects of artemether and lumefantrine include anemia and splenomegaly. Eosinophilia, decreased hematocrit, abnormal lymphocyte morphology, increased and decreased white blood cell count, and increased and decreased platelet count have been reported in some patients as well. Some patients have also suffered from hemolytic anemia (including autoimmune hemolytic anemia) after using this medication.

Hepatic side effects

Though rare, some patients may suffer from jaundice after artemether and lumefantrine treatment. Other hepatic side effects include increased alanine aminotransferase, hepatomegaly and aspartate aminotransferase.

Dermatologic side effects

Dermatologic side effects of artemether and lumefantrine include rashes and pruritus. Urticaria and less serious skin reactions (bullous eruption) are rare dermatologic side effects.

Immunologic side effects

Immunologic side effects of this medication include abscess, bronchitis, acrodermatitis, ear infection, helminthic infection, gastroenteritis, hookworm infection, influenza, impetigo, lower respiratory tract infection, pneumonia, oral herpes, subcutaneous abscess, urinary tract infection and upper respiratory tract infection.

Metabolic side effects

Metabolic side effects of artemether and lumefantrine include hypokalemia. However, this side effect is rare.

Musculoskeletal side effects

Musculoskeletal side effects of this medication are rare. However, they include myalgia and arthralgia. Some patients have also reported gait disturbance and back pain while treating malaria with this medication.

Respiratory side effects

Some patients have reported sore throat and dry cough after using this medication. Patients with asthma may experience pharyngolaryngeal pain while using the medication.

Genitourinary side effects

Genitourinary side effects of the medication include proteinuria and hematuria.

Other side effects have included the following:

  • Loss of appetite
  • Fatigue
  • Weakness and general loss of strength
  • Pins and needles or numb sensations
  • Muscle and joint pains
  • Palpitations
  • Rashes or itching
  • Involuntary muscle contractions
  • Shaky movement or poor control (ataxia)
  • Insomnia
  • Malaise

While most of these side effects may not be life threatening, you should call your doctor or the emergency room if they persist. You may also report these side effects to the Food and Drugs Agency (FDA) at 1-800-FDA-1088.

Artemether and lumefantrine dosage

Follow all the directions on the medication’s prescription label and do not take this medication in larger or small doses, or for longer than prescribed.

It is recommended that you take artemether and lumefantrine with milk, food, pudding or oatmeal. Crush the tablet and mix with 1-2 teaspoons of water for easy swallowing. You may mix the medication with the infant’s formula if you are medicating a child. If you take the medication before food, start eating as soon as possible to help the body absorb the medication faster.

Should you vomit within an hour after taking the medication, consider taking another dose. Call your doctor if the vomiting persists, or if you are unable to eat.

Artemether and lumefantrine is usually administered as a total of six doses over a three-day period. Carefully observe your doctor’s prescription on the number of tablets you should take per dose. Artemether and lumefantrine dosage is based on age and body weight.

The standard doses are as follows, unless otherwise advised by your doctor.

For patients 16 years and older with body weight of at least 77 pounds:

  • The initial dose is 4 tablets
  • Take another 4 tablets after 8 hours
  • Take 4 tablets 12-hours apart (possibly morning and evening) for the next two days

For patients younger than 16 years, and with body weight between 55 and 77 pounds:

  • The initial dose is 3 tablets
  • Take another 3 tablets after 8 hours
  • Take 3 tablets 12-hours apart (morning and evening) for the next two days

For patients younger than 16 years, and with body weight between 33 and 55 pounds:

  • The initial dose is 2 tablets
  • Take another 2 tablets after 8 hours
  • Take 2 tablets 12-hours apart (morning and evening) for the next two days

For patients younger than 16 years, and with body weight between 11 and 33 pounds:

  • The initial dose is 1 tablet
  • The second tablet should be taken after 8 hours
  • Take 1 tablet 12-hours apart (morning and evening) for the next two days

Renal dose adjustments

There is no recommended renal dose adjustment. However, the manufacturer recommends caution when administering this mediation to a patient with severe renal dysfunction.

Liver adjustment

No adjustment is recommended for patients with mild to moderate hepatic impairment. That said, there is no data available for administration of this medication to patients with severe hepatic impairment. The manufacturer, therefore, advises caution when administering the medication to patients with severe liver problems.

Artemether and lumefantrine overdose

It is unlikely that an overdose will occur if this medication is administered in a medical setting by a healthcare provider. Call your healthcare provider or local Poison Control Center if you take too much artemether and lumefantrine.

Artemether and lumefantrine interactions

Artemether and lumefantrine co-administration with strong CYP450 3A4 inducers like carbamazepine, rifampin, St. John’s wort and phenytoin may decrease the levels of artemether and lumefantrine to result in loss of its antimalarial efficacy. In addition, administering the medication alongside CYP450 3A4 substrate may decrease the concentration of the substrate with potential loss of the substrate’s efficacy.

Administering artemether and lumefantrine alongside CYP450 3A4 inhibitors such as grapefruit juice may increase the levels of artemether and/or lumefantrine while potentiating QT prolongation.

Administering the medication together with CYP450 3A4 inducers may lower the levels of artemether and/or lumefantrine to result in loss of its antimalarial efficacy.

Antiretroviral medications that counter the efficacy of CYP450 3A4 such as non-nucleoside reverse transcriptase inhibitors and HIV protease inhibitors should be taken with caution during artemether and lumefantrine medication.

Artemether and lumefantrine have been linked to prolongation of the QT interval on electrocardiogram. Therefore, artemether and lumefantrine should be avoided by patients with congenital prolongation or the QT interval or any other condition that might prolong the QT interval like a history of symptomatic cardiac arrhythmias, severe cardiac disease or clinically relevant bradycardia. Patients with a family history of sudden death or congenital prolongation of the QT interval should also avoid this medication.

Other patients who should avoid artemether and lumefantrine include:

  • Those with known electrolyte balance disturbances like hypomagnesemia and hypokalemia
  • Those on medications that prolong the QT interval like antipsychotics, class IA and class III antiarrhythmics, antidepressants, antibiotics like imidazole, macrolides, triazole antifungals and fluoroquinolones, and cisapride.
  •  Those on medications that affect the QT interval

Due to lumefantrine’s long elimination half-life coupled with its potential addictive effects on QT interval, artemether and lumefantrine should never be administered with halofantrine within 4 weeks of each other. In addition, medications that prolong QT interval, such as quinidine and quinine, should be administered with caution to a patient who is on artemether and lumefantrine medication.

Reduced exposure, and efficacy, of lumefantrine may occur if a patient uses mefloquine immediately prior to artemether and lumefantrine. This is possibly because mefloquine induces a reduction in bile secretion. The patient should be monitored for reduced efficacy and advised to consume food while on artemether and lumefantrine medication.

Food boosts artemether and lumefantrine absorption, and efficacy. A patient who is averse to food during medication should be closely monitored due to increased risk of recrudescence. A treatment with a different antimalarial is recommended in the event of recrudescent.

Artemether and lumefantrine have been associated with various hypersensitivity reactions. The medication should be discontinued at the earliest sign of urticaria, skin rash or any other kind of skin reaction, breathing and swallowing difficulty, tachycardia, any swelling indicative of angioedema, as well as other signs of allergic reactions.

Data on the effectiveness of artemether and lumefantrine for treatment against the erythrocyte stage of Falciparum vivax is limited. Thus, relapsing malaria that is caused by this protozoan may require additional treatment with other antimalarial medications.

The efficacy of artemether and lumefantrine have not been established in the treatment of expectant mothers with acute or uncomplicated malaria. In addition, the safety and effectiveness of this medication has not been established in patients who weigh less than 11 pounds (5 kg).

Artemether and Lumefantrine Food Interactions

Patients are advised to avoid grapefruit juice while on artemether and lumefantrine medication. This is because grapefruit juice can cause too much medicine in the patient’s blood.

Pregnancy and breastfeeding

Certain medications are never safe for use by pregnant and breastfeeding mothers. However, other medications may be safe for use during these times provided the benefits to the mother outweigh the risks to the unborn baby or the infant. Inform your healthcare provider if you are pregnant or breastfeeding before using this, or any other medication.

  • The safety of artemether and lumefantrine to the unborn baby is yet to be established. This medication should be avoided whenever possible during the first trimester of pregnancy. It should only be administered later in the pregnancy if the benefits to the mother far outweigh the risks to the unborn baby. Seek direction from your healthcare provider.
  • It is not clear if artemether and lumefantrine passes into breast milk. Women who are nursing should avoid breastfeeding while on this medication, and for at least one week after the last dose. Seek direction from your healthcare provider on use of this medication while breastfeeding.

Artemether and lumefantrine interactions with other medications

Inform your pharmacist or healthcare provider of any other medication you are already taking, including over-the-counter prescriptions, supplements, and herbal medications. Similarly, check with your healthcare provider before taking any medication alongside artemether and lumefantrine.

As already indicated, the manufacturer of this medication states that it should never be taken in combination with other antimalarial medications due to unavailability of data on efficacy and safety of combination treatment.

The following medications should not be taken in combination with artemether and lumefantrine because it may increase the level of these medications in the blood to trigger possible side effects:

  • Metoprolol
  • Imipramine
  • Amitriptyline
  • Flecainide
  • Clomipramine

The manufacturer cautions against use of artemether and lumefantrine in combination with the following medications because such combinations may increase the patient’s risk of developing abnormal heart rhythms.

  • Medications for irregular cardiac rhythms such as propafenone, mexiletine, procainamide, amiodarone, disopyramide, sotalol and quinidine
  • Antidepressant medications like maprotiline, amitriptyline, and fluoxetine
  • Antipsychotic medications like thioridazine, chlorpromazine, and haloperidol
  • Antihistamines like terfenadine and astemizole
  • Cisapride
  • Some anti-infectives like clarithromycin, erythromycin, moxifloxacin, ketoconazole, voriconazole and pentamidine.

Artemether and lumefantrine warnings

  • The patient should take Coartem with or after food to improve its effectiveness. Even if the patient cannot tolerate food, they should still take the medication. The tablets can be crushed or dissolved into water or formula for children and infants.
  • Consult your healthcare provider immediately if you fall sick within one hour of taking this medication. Call for emergency services if you develop breathing difficulty or irregular heartbeats
  • It is important that the patient completes the prescribed dose, unless otherwise directed by the healthcare provider, as the medication may not be fully effective if treatment is incomplete.
  • Unless on approval from your healthcare provider, avoid grapefruit juice while taking this medication for reasons already indicated
  • The medication causes dizziness and general fatigue. The patient should take caution when performing potentially hazardous tasks like driving or operating industrial machinery.
  • Patients who have liver, kidney or heart problems should be closely monitored while on this medication. Potassium levels in the blood as well as heart function should be monitored closely.
  • Never administer this medication to patients who weigh less than 11 pounds (5 kg)

Artemether and lumefantrine storage

Artemether and lumefantrine should be stored in a tight container away from moisture and heat. The medication should be stored at 15 degrees C to 30 degrees C (59 degrees F and 86 degrees F). Store the medicine out of reach of children and pets. Keep away from direct sunlight. All unused and expired medications should be disposed of appropriately.

Summary

Artemether and lumefantrine is a prescription medication used for treatment of mild malaria. It belongs to a group of drugs called antimalarial agents. Artemether and lumefantrine works by blocking nucleic acid and protein synthesis to disrupt the growth of malaria causing Plasmodium falciparum.

Artemether and lumefantrine (brand name Coartem) is only used for treating malaria. It should never be taken to prevent the disease. The medication comes in tablet form and is taken orally with food, water, or pudding. However, patients are advised to avoid grapefruit juice while on this medication.

Artemether and lumefantrine dosage is determined by the patient’s age and body weight. The medication must never be administered to infants whose body weights are less than 11 pounds (5 kg). In addition, concomitant use of this medication alongside other antimalarials is not recommended unless advised otherwise by your healthcare provider.

Patients on artemether and lumefantrine treatment may exhibit a range of side effects. Most of these side effects are mild and may not require medical attention. However, other side effects like irregular heartbeats and breathing difficulty may require the patient to contact emergency services.

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Last Reviewed:
December 25, 2017
Last Updated:
December 22, 2017
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