artemether-lumefantrine

artemether-lumefantrine

(ar-te-meth-er loo-me-fan-treen) ,

Coartem

(trade name)

Classification

Therapeutic: antimalarials
Pregnancy Category: C

Indications

Treatment of acute, uncomplicated malaria in patients ≥5 kg.Not approved for severe/complicated P. falciparum malaria or prevention.

Action

Consists of a fixed ratio of 1:6 parts of artemether and lumefantrine, respectively. Artemether is a prodrug that is rapidly converted to dihydroartemisinin (DHA), its active metabolite. Both components inhibit nucleic acid and protein synthesis.

Therapeutic effects

Antimalarial activity directed at the erythrocytic stages of Plasmodium falciparum.

Pharmacokinetics

Absorption: Well absorbed following oral administration, food increases absorption. Artemether is a prodrug that is rapidly converted to Dihydroartemisinin (DHA), an active antimalarial compound.
Distribution: Unknown.
Protein Binding: Lumefantrine—99.7%.
Metabolism and Excretion: Extensively metabolized by the liver. Artemether is primarily metabolized by CYP3A4/5. Lumefantrine is metabolized mainly by CYP3A. Lumefantrine also significantly inhibits CYP2D6.
Half-life: Artemether and DHA—2 hr; lumefantrine—3–6 days.

Time/action profile (antimalarial effect)

ROUTEONSETPEAK†DURATION
artemether POunknown2 hrhrs
lumefantrine POunknown6–8 hrdays
†blood levels

Contraindications/Precautions

Contraindicated in: Hypersensitivity to artemether or lumefantrine; Known QTc prolongation, conditions or medications associated with QTc prolongation, hypokalemia, or hypomagnesemia; Concurrent use of strong CYP3A4 inducers
Use Cautiously in: Severe hepatic/renal impairment; Concurrent use of medications that are metabolized by the cytochrome enzyme CYP2D6 and/or also have cardiac effects; Geriatric: Use cautiously in elderly patients; consider age-related decreased hepatic, renal, or cardiac function, and concomitant disease concurrent drug therapy; Lactation: Benefits of breastfeeding to mother and infant should be weighed against potential risk from infant exposure to artemether and lumefantrine through breast milk; Obstetric: Use during pregnancy only if potential benefit justifies the potential risk to the fetus; Pediatric: Safety and efficacy not established in children <5 kg.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • sleep disorder (most frequent)
  • weakness (most frequent)
  • insomnia
  • malaise

Ear, Eye, Nose, Throat

  • vertigo

Respiratory

  • cough

Cardiovascular

  • palpitations (most frequent)

Gastrointestinal

  • abdominal pain (most frequent)
  • anorexia (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • diarrhea
  • hepatomegaly
  • splenomegaly

Dermatologic

  • pruritus

Hematologic

  • anemia

Musculoskeletal

  • arthrlagia (most frequent)
  • myalgia (most frequent)

Miscellaneous

  • hypersensitivity reactions including urticaria and angioedema (life-threatening)
  • chills (most frequent)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Concurrent use with strong CYP3A4 inducers including rifampin, carbamazepine, or phenytoin, may ↓ levels and efficacy; concurrent use contraindicatedConcurrent use other antimalarials should be avoided due to lack of safety data.Concurrent use with any other drugs that prolong QTc interval 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 ); should be avoided. CYP3A4 inhibitors may ↑ levels and the risk of QT interval prolongation. Effectiveness may be ↓ by mefloquine if used immediately before treatment (encourage food consumption).May ↓ effectiveness of hormonal contraceptives (additional method of birth control should be used).Concurrent use of antiretrovirals may ↑ risk of QTc prolongation, ↓ anti-retroviral efficacy, or ↓ antimalarial efficacy.Concurrent use of CYP2D6 substrates including flecainide, imipramine, amitriptyline and clomipramine may ↑ risk of adverse reactions and/or ↑ risk of QTc prolongation; avoid concurrent use.St. John's wort may ↓ concentrations; concurrent use contraindicatedGrapefruit juicemay ↑ blood levels and risk of QTc prolongation and should be avoided.

Route/Dosage

Oral (Adults ≥ 35 kg) 4 tablets per dose for a total of 6 doses; given as two doses 8 hours apart on the first day, then twice daily for the next two days.
Oral (Children 25 – <35 kg) 3 tablets per dose for a total of 6 doses; given as two doses 8 hours apart on the first day, then twice daily for the next two days.
Oral (Children 15 – <25 kg) 2 tablets per dose for a total of 6 doses; given as two doses 8 hours apart on the first day, then twice daily for the next two days.
Oral (Children 5 – <15 kg) 1 tablet per dose for a total of 6 doses; given as two doses 8 hours apart on the first day, then twice daily for the next two days.

Availability

Tablets: 20 mg artemether/120 mg lumefantrine

Nursing implications

Nursing assessment

  • Assess patient for improvement in signs and symptoms of malaria (fever, chills, muscle pains, headache) periodically during therapy.
  • Lab Test Considerations: May cause ↑ AST, ↑ ALT, ↓ hematocrit, ↑ or ↓ WBC, ↑ or ↓ platelet count, and eosinophilia.
    • May cause hypokalemia.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • Oral: Administer with food. Tablets may be crushed and mixed with 1–2 tsp water immediately before administration 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 increases 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

  • Instruct patient to take medication as directed. Advise patient to resume eating as soon as food can be tolerated; improves absorption of medication. Advise patient to notify health care professional 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 professional if they have taken other medications to treat malaria recently.
  • Advise patient to avoid drinking grapefruit juice during therapy; may cause increased 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 professional if symptoms of prolongation of the QT interval (prolonged heart palpitations, loss of consciousness) occur.
  • Instruct patient to notify health care professional immediately if signs of hypersensitivity (skin rash, hives, other skin reactions, rapid heartbeat, difficulty breathing or swallowing, swelling of the lips, tongue, face, tightness or throat, hoarseness) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
  • Review methods of minimizing exposure to mosquitoes with patient.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Medication may cause loss of pregnancy and decreased effectiveness of hormonal contraceptives; advise patient to use a non-hormonal form of birth control during therapy.

Evaluation/Desired Outcomes

  • Resolution of fever and clearance of parasites from blood.
References in periodicals archive ?
Artemether-lumefantrine (coartem) produces degeneration in the liver cells as evidenced by liver sections and upsurge in the level of transaminases (Solomon et al., 2013; Theophilus et al., 2012).
All patients were treated empirically with praziquantel for schistosomiasis and at least 1 dose of artemether-lumefantrine for malaria before departure.
Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uige Provinces, Angola.
Suleman, "Assessment of therapeutic efficacy and safety of artemether-lumefantrine (Coartem[R]) in the treatment of uncomplicated Plasmodium falciparum malaria patients in Bahir Dar district, Northwest Ethiopia: An observational cohort study," Malaria Journal, vol.
Rosenthal, "Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda," The Journal of Infectious Diseases, vol.
An assessment of the quality of artemether-lumefantrine preparations and artemether injections in Cape Coast Metropolis, Ghana, showed that 7 (87.5%) of the 8 brands (6 tablets, 2 suspensions) and all 2 artemether injections passed the International Pharmacopoeia content test [12].
It was thus predicted that removal of CQ and SP pressure from the Cameroon population and introduction of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) [5] will lead to a gradual reduction of the CQ and SP resistant genotypes.
The knowledge of the respondents on the ACTs was appreciable, but artesunate-amodiaquine (92%) and artemether-lumefantrine (87%) were the most common among the respondents (Table 3).