Drug information of Lumefantrine / artemether

Lumefantrine / artemether

Drug group: Antimalarials

Lumefantrine used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.

Mechanism of effect

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of β-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamic

Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

Pharmacokinetics

  • Absorption: Food increases absorption.
  • Volume of distribution: Not Available
  • Protein binding: 99.7% bound
  • Route of elimination: Not Available
  • Half life: ~ 4.5 days
  • Metabolism: Extensively metabolized in the liver primarily by cytochrome P450 3A4. The major metabolite found in plasma is desbutyl-lumefantrine.

Drug indications

Treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum.

Dosage

Treatment of uncomplicated malaria:

Three-day schedule: Oral:

Adults

Patients 25 to <35 kg: Three tablets at hour 0 and hour 8 on the first day, then 3 tablets twice daily on day 2 and day 3 (total of 18 tablets per treatment course)

Patients ≥35 kg: Four tablets at hour 0 and hour 8 on the first day, then 4 tablets twice daily on day 2 and day 3 (total of 24 tablets per treatment course)

Infants ≥2 months, Children, and Adolescents ≤16 years:

5 to <15 kg: One tablet at hour 0 and hour 8 on the first day, then 1 tablet twice daily on day 2 and day 3 (total of 6 tablets per treatment course)

15 to <25 kg: Two tablets at hour 0 and hour 8 on the first day, then 2 tablets twice daily on day 2 and day 3 (total of 12 tablets per treatment course)

25 to <35 kg: Three tablets at hour 0 and hour 8 on the first day, then 3 tablets twice daily on day 2 and day 3 (total of 18 tablets per treatment course).

≥35 kg: Four tablets at hour 0 and hour 8 on the first day, then 4 tablets twice daily on day 2 and day 3 (total of 24 tablets per treatment course)

Adolescents >16 years: Refer to adult dosing.

Drug contraindications

Hypersensitivity to this drug or components

Hypersensitivity to artemether, lumefantrine, or any component of the formulation; concurrent use with strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, St John’s wort).

Side effects

sleep disorder , Pain , Headache , nausea , vomiting , vertigo , palpitations , fever , anorexia , weakness , tiredness , joint or muscle pain , Abdominal pain

Cardiovascular: Palpitation (adults: 18%)
Central nervous system: Headache (adults 56%; children 13%), dizziness (adults 39%; children 4%), fever (25% to 29%), chills (adults 23%; children 5%), sleep disorder (adults: 22%), fatigue (adults 17%; children 3%)

Gastrointestinal: Anorexia (adults 40%; children 13%), nausea (adults 26%; children 5%), vomiting (17% to 18%), abdominal pain (8% to 17%) Infection: Plasmodium falciparum (exacerbation: children: 17%)
Neuromuscular & skeletal: Weakness (adults 38%; children 5%), arthralgia (adults 34%; children 3%), myalgia (adults 32%; children 3%)
Respiratory: Cough (adults 6%; children 23%)
Miscellaneous: Fever (25% to 29%)

Antiarrhythmics, class IA or III: Possible additive effects on prolongation of QT interval.
Anticonvulsants (Carbamazepine, phenytoin): Possible decreased concentrations of artemether and/or lumefantrine; possible loss of antimalarial efficacy.
Antidepressants known to prolong QT interval: Possible additive effects on prolongation of QT interval.
Anti-infectives known to prolong QT interval (e.g., macrolides, fluoroquinolones, imidazole- or triazole-derivative antifungal agents): Possible additive effects on prolongation of QT interval.
Ketoconazole: Increased concentrations of artemether, active metabolite of artemether, and lumefantrine; increased risk of QT.
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 mefloquine.
Quinidine: Possible additive effects on prolongation of QT interval.
Quinine: possible additive effects on prolongation of QT interval.
Antipsychotics known to prolong QT interval (e.g., pimozide, ziprasidone): Possible additive effects on prolongation of QT interval.
Grapefruit Juice: Possible increased artemether and/or lumefantrine concentrations; possible increased risk of prolonged QT interval.
HIV protease inhibitors (PIs): Possible decreased antimalarial efficacy and increased risk of QT prolongation.
Hormonal contraceptives: Oral, transdermal, or other hormonal contraceptives: Possible decreased effectiveness of the hormonal contraceptive.
Nonnucleoside reverse transcriptase inhibitors (NNRTIs): Possible decreased antimalarial efficacy and increased risk of QT prolongation.
Rifampin: Decreased AUC of artemether, active metabolite of artemether, and lumefantrine.

Alerts

  • QT prolongation: Use associated with prolonging the QT interval; avoid use in patients at risk for QT prolongation, including patients with a history of long QT syndrome, family history of congenital QT prolongation or sudden death, symptomatic arrhythmias, clinically relevant bradycardia, severe heart disease, known hypokalemia, hypomagnesemia or concurrent administration of antiarrhythmics (eg, Class Ia or III), drugs metabolized by CYP2D6 known to have cardiac effects (eg, flecainide, tricyclic antidepressants), or other drugs known to prolong the QT interval (eg, antipsychotics, antidepressants, macrolides, fluoroquinolones, triazole antifungals, or cisapride).
  • Hepatic impairment: Use caution in patients with severe hepatic impairment; has not been adequately studied.
  • Renal impairment: Use caution in patients with severe renal impairment; has not been adequately studied.
  • Appropriate use: Not indicated for the treatment of severe or complicated malaria or for the prevention of malaria.
  • Recrudescence: In the event of disease reappearance after a quiescent period, patients should be treated with a different antimalarial drug.

Points of recommendation

You should not use this medication if you are allergic to  lumefantrine.

Some medicines can interact with lumefantrine and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • rifampin;
  • John's wort; or
  • seizure medicine--carbamazepine, phenytoin.

Tell your doctor about all other anti-malaria medications you have used within the past.

To make sure lumefantrine is safe for you, tell your doctor if you have ever had:

  • heart disease;
  • long QT syndrome (in you or a family member);
  • liver or kidney disease;
  • low levels of potassium or magnesium in your blood.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Use a barrier form of birth control (condom or diaphragm with spermicide). Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

It is not known whether artemether and lumefantrine passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Take artemether and lumefantrine with food, milk, pudding, oatmeal, or broth. The tablet may be crushed and mixed with 1 or 2 teaspoons of water for easier swallowing. You may also mix a crushed tablet with infant formula when giving this medication to a child. Start eating normally as soon as possible to help your body better absorb the medication.

If you vomit within 1 hour after taking this medication, take another dose. If your vomiting continues or you cannot eat, call your doctor.

Artemether and lumefantrine is usually given as a total of 6 doses over a period of 3 days. Carefully follow your doctor's instructions about how many tablets to take per dose. Artemether and lumefantrine doses are based on weight and age.

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.

Pregnancy level

C


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