artemether/lumefantrine

Absorption: Well absorbed following oral administration; food ↑ absorption. Artemether is a prodrug that is rapidly converted to dihydroartemisinin (DHA), an active antimalarial compound.

Distribution: Unknown.

Protein Binding: Lumefantrine: 99.7%.

Metabolism/Excretion: Extensively metabolized by the liver. Artemether is primarily metabolized by the liver via the CYP3A4/5 isoenzymes. Lumefantrine is metabolized mainly by the CYP3A isoenzyme.

Half-Life: Artemether and dihydroartemisinin: 2 hr; lumefantrine: 3–6 days.

Time/Action Profile ⬆ ⬇

(antimalarial effect)

ROUTE	ONSET	PEAK‡	DURATION
Artemether PO	unknown	2 hr	hrs
Lumefantrine PO	unknown	6–8 hr	days

‡Plasma concentrations.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to artemether or lumefantrine;
Known QTc interval prolongation, conditions or medications associated with QTc interval prolongation, hypokalemia, or hypomagnesemia;
Concurrent use of strong CYP3A4 inducers.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <5 kg (safety and effectiveness not established);
Geri: Consider age-related ↓ in hepatic, renal, or cardiac function, and concurrent disease or drug therapy.

Adv. Reactions/Side Effects ⬆ ⬇

CV: palpitations

Derm: pruritus

EENT: vertigo

GI: abdominal pain, anorexia, nausea, vomiting, diarrhea, hepatomegaly, splenomegaly

GU: ↓fertility

Hemat: anemia

MS: arthralgia, myalgia

Neuro: dizziness, fatigue, headache, sleep disorder, weakness, insomnia, malaise

Resp: cough

Misc: chills, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, URTICARIA, AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, carbamazepine, or phenytoin, may ↓ levels and effectiveness; concurrent use contraindicated.
Concurrent use with other antimalarials should be avoided due to lack of safety data.
QT interval prolonging drugs, including quinine, class IA antiarrhythmics (quinidine, procainamide, disopyramide), class III antiarrhythmics (amiodarone, sotalol), antipsychotics (pimozide, ziprasidone), antidepressants, or certain anti-infectives (macrolides, fluoroquinolones, imidazoles/triazoles), may ↑ risk of QT interval prolongation; avoid concurrent use.
CYP3A4 inhibitors may ↑ levels and risk of toxicity.
Mefloquine may ↓ effectiveness if used immediately before treatment.
May ↓ effectiveness of hormonal contraceptives.
Concurrent use of antiretrovirals may ↑ risk of QTc interval prolongation, ↓ antiretroviral efficacy, or ↓ antimalarial efficacy.
May ↑ levels and risk of toxicity of CYP2D6 substrates, including flecainide, imipramine, amitriptyline, and clomipramine.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; concurrent use contraindicated.

Drug-Food:

Grapefruit juicemay ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥35 kg): Artemether 80 mg/lumefantrine 480 mg twice daily for 3 days (1st 2 doses should be separated by 8 hr).
PO (Children 25–<35 kg): Artemether 60 mg/lumefantrine 360 mg twice daily for 3 days (1st 2 doses should be separated by 8 hr).
PO (Children 15–<25 kg): Artemether 40 mg/lumefantrine 240 mg twice daily for 3 days (1st 2 doses should be separated by 8 hr).
PO (Children 5–<15 kg): Artemether 20 mg/lumefantrine 120 mg twice daily for 3 days (1st 2 doses should be separated by 8 hr).

Availability ⬆ ⬇

Tablets: artemether 20 mg/lumefantrine 120 mg

Assessment ⬆ ⬇

Assess patient for improvement in signs/symptoms of malaria (fever, chills, muscle pains, headache) periodically during therapy.
Assess cardiac history and ECG at baseline.

Lab Test Considerations:

Perform Giemsa-stained thick and thin blood films to confirm malaria parasite within 12 hr of presentation of patients with suspected malaria. Repeat blood films are recommended at 12–24 hr intervals for 48–72 hr if original thin film is negative and patient is suspected to have malaria. Repeat after at ≥28 days is recommended, as resolution of fever is not confirmation of cure of malaria.
May cause ↑ AST, ↑ ALT, ↓ hematocrit, ↑ or ↓ WBC, ↑ or ↓ platelet count, and eosinophilia.
- May cause hypokalemia.

Implementation ⬆ ⬇

PO: Administer with food. Tablets may be crushed and mixed with 5–10 mL of water for patients with difficulty swallowing. Rinse container with more water and have patient swallow contents. Follow with food or drink (milk, formula, pudding, broth, porridge) if possible. Lack of adequate food ↑ risk for malaria relapse.
If vomiting occurs within 1–2 hr of administration, repeat dose. If repeat dose is vomited, use an alternative antimalarial.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of artemether/lumefantrine. Instruct patient to take as directed. Advise patient to resume eating as soon as food can be tolerated; ↑ absorption of medication. Advise patient to notify health care provider of flu-like symptoms (chills, fever, muscle pains, headache) occur again after finishing medication. Instruct patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care provider if they have taken other medications to treat malaria recently.
Advise patient to avoid drinking grapefruit juice during therapy; may cause ↑ concentrations and risk of arrhythmias.
May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider if symptoms of prolongation of the QT interval (prolonged heart palpitations, loss of consciousness) occur.
Advise patients and family to call 911 and seek urgent treatment for signs/symptoms of hypersensitivity reactions (difficulty breathing; chest tightness; hives; rash; light-headedness; itching; swelling of the face, lips, tongue, or throat).
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications, especially St. John's wort.
Review methods of minimizing exposure to mosquitoes with patient.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Medication may cause ↓ effectiveness of hormonal contraceptives; advise patient to use a nonhormonal form of birth control during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇