Artemether and lumefantrine

Name: Artemether and lumefantrine

What is artemether and lumefantrine?

Artemether and lumefantrine are anti-malaria medications that interfere with the growth of parasites in the red blood cells of the human body. Malaria is caused by parasites that enter the body through the bite of a mosquito. Malaria is common in areas such as Africa, South America, and Southern Asia.

Artemether and lumefantrine is a combination medicine used to treat non-severe malaria.

This medication is used only to treat malaria. Do not use artemether and lumefantrine to prevent malaria.

Artemether and lumefantrine may also be used for purposes not listed in this medication guide.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should I avoid while taking artemether and lumefantrine?

Avoid taking other anti-malaria medications, unless your doctor has told you to.

Grapefruit and grapefruit juice may interact with artemether and lumefantrine and lead to unwanted side effects. Avoid the use of grapefruit products while taking artemether and lumefantrine.

What other drugs will affect artemether and lumefantrine?

Many drugs can interact with artemether and lumefantrine. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • other anti-malaria medications;

  • antibiotics or medicine to treat tuberculosis;

  • an antidepressant;

  • antipsychotic medication;

  • birth control pills or hormone replacement therapy;

  • heart rhythm medication;

  • antiviral medicine to treat HIV or AIDS; or

  • seizure medication or medicine for nerve pain in your face.

This list is not complete and many other drugs can interact with artemether and lumefantrine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Interactions for Artemether and Lumefantrine

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Artemether: Metabolized predominantly by CYP 3A4/5 isoenzyme and, to a lesser extent, by CYP isoenzymes 2B6, 2C9, and 2C19.1 May be a weak inducer of CYP isoenzymes 2C19, 2B6, and 3A4.1 Does not inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.1

Lumefantrine: Metabolized principally by CYP3A4.1 Inhibits CYP2D6.1

Potential pharmacokinetic interactions with drugs metabolized by CYP3A4 (decreased concentrations of CYP3A4 substrate).1

Potential pharmacokinetic interactions with drugs that inhibit or induce CYP3A4 (altered metabolism of artemether and/or lumefantrine).1

Potential pharmacokinetic interactions with CYP2D6 (increased concentrations of CYP2D6 substrate).1 Avoid concurrent use with drugs that are CYP2D6 substrates and are known to have cardiac effects (e.g., flecainide, imipramine, amitriptyline, clomipramine).1

Drugs that Prolong the QT Interval

Additive effect on the QT interval might occur if artemether/lumefantrine used with other agents that prolong the QT interval;1 avoid concomitant use.1

Avoid concomitant use with class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), class III antiarrhythmic agents (e.g., amiodarone, sotalol), antipsychotics (e.g., pimozide, ziprasidone), antidepressants, certain other antimalarials (e.g., quinine, quinidine, halofantrine [not commercially available in US]), and certain anti-infectives (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents).1 Also avoid concomitant use with drugs metabolized by CYP2D6 that can prolong QT interval (e.g., flecainide, imipramine, amitriptyline, clomipramine).1

If concomitant use with drugs that prolong the QT interval considered medically necessary, monitor ECGs.1

Specific Drugs

Drug

Interaction

Comments

Antiarrhythmics, class IA or III

Possible additive effects on prolongation of QT interval1

Avoid concomitant use with drugs known to prolong QT interval1

Anticonvulsants

Carbamazepine, phenytoin: Possible decreased concentrations of artemether and/or lumefantrine; possible loss of antimalarial efficacy1

Carbamazepine, phenytoin: Concomitant use contraindicated1

Antidepressants known to prolong QT interval

Possible additive effects on prolongation of QT interval1

Avoid concomitant use with drugs known to prolong QT interval1

Anti-infectives known to prolong QT interval (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents)

Possible additive effects on prolongation of QT interval1

Ketoconazole: Increased concentrations of artemether, active metabolite of artemether, and lumefantrine;1 12 increased risk of QT prolongation1

Avoid concomitant use with drugs known to prolong QT interval1

Ketoconazole: Dosage adjustment for artemether/lumefantrine not needed;1 12 use concomitantly with caution1

Antimalarial agents

Antimalarial agents: Safety data on concomitant use limited1

Mefloquine: Decreased concentrations and AUC of lumefantrine possibly as the result of mefloquine-induced decrease in bile production; no effect on pharmacokinetics of artemether or mefloquine1 146

Quinidine: Possible additive effects on prolongation of QT interval1

Quinine: Pharmacokinetic interaction unlikely;1 13 possible additive effects on prolongation of QT interval1

Halofantrine (not commercially available in US): Possible additive effects on QT interval1

Antimalarial agents: Concurrent use not recommended unless there are no other treatment options1

Mefloquine: If artemether/lumefantrine given shortly after mefloquine, take dose with food and monitor for effectiveness1

Quinidine: Caution advised if quinidine administered after artemether/lumefantrine; monitor ECG1

Quinine: Caution advised if quinine administered after artemether/lumefantrine; monitor ECG1

Halofantrine: Allow one month to elapse between administration of halofantrine and artemether/lumefantrine and vice versa1

Antipsychotics known to prolong QT interval (e.g., pimozide, ziprasidone)

Possible additive effects on prolongation of QT interval1

Avoid concomitant use with drugs known to prolong QT interval1

Grapefruit Juice

Possible increased artemether and/or lumefantrine concentrations; possible increased risk of prolonged QT interval1

Avoid concomitant use1

HIV protease inhibitors (PIs)

PIs: Possible decreased antimalarial efficacy and increased risk of QT prolongation1

Ritonavir-boosted darunavir: Decreased AUC of artemether and active metabolite of artemether; increased AUC of lumefantrine; no effect on darunavir or ritonavir AUC14

Lopinavir/ritonavir: Decreased AUC of artemether and active metabolite of artemether; increased AUC of lumefantrine; no effect on lopinavir AUC1 9

PIs: Use concomitantly with caution.1

Hormonal contraceptives

Oral, transdermal, or other hormonal contraceptives: Possible decreased effectiveness of the hormonal contraceptive1

Use additional nonhormonal methods of contraception1

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

NNRTIs: Possible decreased antimalarial efficacy and increased risk of QT prolongation1

Efavirenz: Decreased AUC of artemether, active metabolite of artemether, and lumefantrine; no effect on efavirenz AUC1 15

Etravirine: Decreased AUC of artemether, active metabolite of artemether, and lumefantrine; no effect on etravirine AUC14

NNRTIs: Use concomitantly with caution1

Rifampin

Decreased AUC of artemether, active metabolite of artemether, and lumefantrine1

Concomitant use contraindicated1

Uses of Artemether and Lumefantrine

  • It is used to treat malaria.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Artemether and Lumefantrine?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Dosing Hepatic Impairment

Dosage adjustments are not recommended in mild or moderate impairment. Use caution in severe impairment (has not been studied).

Usual Pediatric Dose for Malaria

5 kg to less than 15 kg: 1 tablet as single initial dose, followed by 1 tablet after 8 hours, and then 1 tablet twice a day (morning and evening) for the following 2 days (total course: 6 tablets)

15 kg to less than 25 kg: 2 tablets as single initial dose, followed by 2 tablets after 8 hours, and then 2 tablets twice a day (morning and evening) for the following 2 days (total course: 12 tablets)

25 kg to less than 35 kg: 3 tablets as single initial dose, followed by 3 tablets after 8 hours, and then 3 tablets twice a day (morning and evening) for the following 2 days (total course: 18 tablets)

35 kg or more: 4 tablets as single initial dose, followed by 4 tablets after 8 hours, and then 4 tablets twice a day (morning and evening) for the following 2 days (total course: 24 tablets)

Liver Dose Adjustments

Mild to moderate hepatic impairment: No adjustment recommended.
Severe hepatic impairment: No data available; the manufacturer recommends caution when administering this drug to patients with severe liver dysfunction.

Dialysis

Data not available

Artemether / lumefantrine Pregnancy Warnings

Artemether-lumefantrine has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of embryo-fetal loss and fetal defects. Safety data from an observational pregnancy study of approximately 500 pregnant women who were exposed to artemether-lumefantrine (including a third exposed during the first trimester), and published data of over 1000 pregnant patients who were exposed to artemisinin derivatives, did not show an increase in adverse pregnancy outcomes or teratogenic effects over background rate. Artemether-lumefantrine is only recommended for use during pregnancy when benefit outweighs risk.

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