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Artemether and lumefantrine: Drug information

Artemether and lumefantrine: Drug information
(For additional information see "Artemether and lumefantrine: Patient drug information" and see "Artemether and lumefantrine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Coartem
Pharmacologic Category
  • Antimalarial Agent
Dosing: Adult
Malaria, treatment

Malaria, treatment: 3-day schedule: Oral:

Patients ≥35 kg: 4 tablets (based on artemether 20 mg/lumefantrine 120 mg per tablet; additional tablet strengths may be available outside the US) 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).

Note: If used for P. vivax or P. ovale, use in combination with primaquine. If used for severe malaria (after completion of IV therapy), use full 3-day schedule in addition to IV therapy (CDC 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

(For additional information see "Artemether and lumefantrine: Pediatric drug information")

Malaria, treatment; uncomplicated

Malaria, treatment; uncomplicated (due to P. falciparum, including chloroquine resistant P. falciparum): Note: Not for treatment of severe or complicated Plasmodium falciparum malaria or prevention of malaria.

Infants ≥2 months, Children, and Adolescents: Note: Additional tablet strengths may be available outside the US:

Oral (artemether 20 mg/lumefantrine 120 mg per tablet):

5 kg to <15 kg: One tablet at hour 0 and at hour 8 on the first day and then one tablet twice daily (in the morning and evening) on days 2 and 3 (total of 6 tablets per treatment course).

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

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

≥35 kg: Four tablets at hour 0 and at hour 8 on the first day and then four tablets twice daily (in the morning and evening) on days 2 and 3 (total of 24 tablets per treatment course).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

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

Dosing: Hepatic Impairment: Pediatric

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

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Coartem: Artemether 20 mg and lumefantrine 120 mg [scored; contains polysorbate 80]

Generic Equivalent Available: US

No

Administration: Adult

Administer with a full meal for best absorption. For patients unable to swallow tablets: Crush tablet and mix with 5-10 mL of water. Administer to patient. Rinse container with water and administer contents to the patient. The crushed mixture should be followed with food/drink if possible. Repeat dose if vomiting occurs within 2 hours of administration; for persistent vomiting, explore alternative therapy.

Administration: Pediatric

Oral: Administer with a full meal for best absorption. For infants, children, and patients unable to swallow tablets: Crush tablet and mix with 5 to 10 mL of water in a clean container; administer; rinse container with water and administer remaining contents. The crushed mixture should be followed with food/milk, infant formula, pudding, porridge, or broth if possible. Repeat dose if vomiting occurs within 2 hours of administration; for persistent vomiting, explore alternative therapy.

Use: Labeled Indications

Malaria , treatment: Treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum, including geographical regions where chloroquine resistance has been reported. Note: CDC guidelines also recommend artemether/lumefantrine as an alternative agent for chloroquine-sensitive Plasmodium species, for chloroquine-resistant Plasmodium vivax or Plasmodium ovale, and as oral treatment for severe malaria after completion of IV therapy or as interim therapy pending IV therapy (CDC 2020).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

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%)

3% to 10%:

Central nervous system: Insomnia (adults: 5%), malaise (adults: 3%), vertigo (adults: 3%)

Dermatologic: Pruritus (adults: 4%), skin rash (3%)

Gastrointestinal: Diarrhea (7% to 8%)

Hematologic & oncologic: Anemia (4% to 9%)

Hepatic: Hepatomegaly (6% to 9%), increased serum AST (≤4%)

Infection: Malaria (≤3%)

Respiratory: Rhinitis (4%), nasopharyngitis (≤3%)

<3%, postmarketing, and/or case reports: Abnormal gait, abnormal lymphocytes, abscess, agitation, anaphylaxis, angioedema, asthma, ataxia, back pain, bronchitis, bullous dermatitis, change in platelet count (increased), clonus, conjunctivitis, constipation, decreased hematocrit, decreased platelet count, decreased white blood cell count, dermatitis (hands and feet), dyspepsia, dysphagia, emotional lability, eosinophilia, fine motor control disorder, gastroenteritis, helminthiasis, hematuria, hemolytic anemia (delayed), hookworm infection, hyper-reflexia, hypoesthesia, hypokalemia, impetigo, increased serum ALT, influenza, leukocytosis, leukopenia, lower respiratory tract infection, nystagmus, oral herpes, otic infection, peptic ulcer, pharyngolaryngeal pain, pneumonia, proteinuria, respiratory tract infection, subcutaneous abscess, tinnitus, tremor, upper respiratory tract infection, urinary tract infection, urticaria

Contraindications

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

Warnings/Precautions

Concerns related to adverse effects:

• 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).

Disease-related concerns:

• 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.

Concurrent drug therapy issues:

• Drugs that prolong the QT interval: Avoid use in patients receiving other agents that prolong the QT interval; consider alternative therapy. ECG monitoring is advised if concomitant use of agents that prolong the QT interval is medically required. In addition, do not use halofantrine (not available in the US) and artemether/lumefantrine within one month of one another due to the potential additive effects on the QT interval. After discontinuation of artemether/lumefantrine, drugs that prolong the QT interval, including quinidine and quinine, should be used with caution.

• Duplicate therapy: Antimalarials should not be given concomitantly unless there is no other treatment option.

Other warnings/precautions:

• 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.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antimalarial Agents: May enhance the adverse/toxic effect of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider therapy modification

ChlorproMAZINE: Antimalarial Agents may increase the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): Artemether and Lumefantrine may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification

Efavirenz: May decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Efavirenz may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. Grapefruit Juice may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Halofantrine: Artemether and Lumefantrine may enhance the QTc-prolonging effect of Halofantrine. Management: Halofantrine and artemether/lumefantrine should not be used within 1 month of each other. Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Mequitazine: May enhance the QTc-prolonging effect of Artemether and Lumefantrine. Management: Consider alternatives to concomitant use of artemether/lumefantrine and mequitazine when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification

Nevirapine: May decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Nevirapine may decrease the serum concentration of Artemether and Lumefantrine. Nevirapine may increase the serum concentration of Artemether and Lumefantrine. Specifically, lumefantrine concentrations may increase. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy

Protease Inhibitors: May increase the serum concentration of Artemether and Lumefantrine. Specifically, the concentrations of lumefantrine may be increased. Protease Inhibitors may decrease the serum concentration of Artemether and Lumefantrine. Specifically, concentrations of artemether and dihydroartemisinin (DHA), the active metabolite of artemether, may be decreased. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy

St John's Wort: May decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. St John's Wort may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination

Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification

Food Interactions

Absorption of artemether and lumefantrine is increased in the presence of food. The bioavailability of artemether increases two- to threefold and lumefantrine increases 16-fold (particularly a high-fat meal). Administration with grapefruit juice may result in increased concentrations of artemether and/or lumefantrine and potentiate QT prolongation. Management: Administer with a full meal for maximal absorption. Avoid grapefruit juice.

Reproductive Considerations

Artemether may reduce the effectiveness of hormonal contraceptives. An additional nonhormonal method of birth control should be used during therapy.

Pregnancy Considerations

A meta-analysis of observational pregnancy studies, which included 500 pregnant women exposed to artemether/lumefantrine in their first trimester, and data from observational and open-label studies of >1,200 pregnant women exposed to artemether/lumefantrine in their second or third trimesters have not shown an increased risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes.

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020; CDC Yellow Book 2020).

Artemether/lumefantrine may be used to treat chloroquine resistant uncomplicated malaria during the second and third trimesters. Artemether/lumefantrine also may be used as an alternative treatment during the first trimester when preferred agents are not available. In pregnant patients with severe malaria, artemether/lumefantrine is the preferred interim oral therapy when the preferred IV agent is not readily available (discontinue once IV treatment is initiated). Dosing is the same as nonpregnant patients (Ballard [CDC 2018]; CDC 2020).

Breastfeeding Considerations

It is not known if artemether or lumefantrine are present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. The CDC does not recommend use of this combination when breastfeeding infants weighing <5 kg (CDC Yellow Book 2020).

Dietary Considerations

Administer with a full meal for best absorption. Patients should be encouraged to take with a meal as soon as food can be tolerated. Patients who remain averse to food during treatment should be closely monitored as the risk of recrudescence may be great.

Monitoring Parameters

Monitor patients for adequate food consumption (to ensure absorption and efficacy); ECG monitoring is advised if concomitant use of other agents that prolong the QT interval is medically required

Mechanism of Action

A coformulation of artemether and lumefantrine with activity against Plasmodium falciparum. Artemether and major metabolite dihydroartemisinin (DHA) are rapid schizontocides with activity attributed to the endoperoxide moiety common to each substance. Artemether inhibits an essential calcium adenosine triphosphatase. The exact mechanism of lumefantrine is unknown, but it may inhibit the formation of β-hematin by complexing with hemin. Both artemether and lumefantrine inhibit nucleic acid and protein synthesis. Artemether rapidly reduces parasite biomass and lumefantrine eliminates residual parasites.

Pharmacokinetics

Absorption: Artemether: Rapid; Lumefantrine: Initial absorption at 2 hours; enhanced with food

Protein binding: Artemether: 95%; Dihydroartemisinin (DHA): 47% to 76%; Lumefantrine: 99.7%

Metabolism:

Artemether is hepatically metabolized to an active metabolite, dihydroartemisinin (DHA), catalyzed predominately by CYP3A4/5 and to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. The artemether/DHA AUC ratio is 1.2 after 1 dose and 0.3 after 6 doses which may indicate autoinduction.

Lumefantrine is hepatically metabolized to desbutyl-lumefantrine by CYP3A4.

Bioavailability: Absorption of artemether and lumefantrine is increased in the presence of food. The bioavailability of artemether increases two- to threefold and lumefantrine increases 16-fold (particularly a high-fat meal).

Half-life elimination: Artemether: 1-2 hours; DHA: 2 hours; Lumefantrine: 72-144 hours

Time to peak, plasma: Artemether: ~2 hours; Lumefantrine: ~6-8 hours

Pricing: US

Tablets (Coartem Oral)

20-120 mg (per each): $6.13

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Amblum (PK);
  • Artefan (TZ, ZW);
  • Artemelatrin (EG);
  • Artemet (SY);
  • Artemether-Plus (VN);
  • Co-Lutem (VN);
  • Coartem (ET, ID, KW, PE, PH, QA, VN, ZA, ZW);
  • Coavlon (BD);
  • Combiart (TZ);
  • Etharine (BD);
  • Exafal (PK);
  • Komefan (ZW);
  • Lumartem (ET, ZW);
  • Lumertam (BD);
  • Malaricure (EG);
  • Malfan (BD);
  • Riamet (AT, AU, BE, CH, CZ, DE, ES, FR, GB, GR, JP, MY, NL, NO, NZ, PT, SE, SG, SI)


For country code abbreviations (show table)
  1. Alecrim MG, Lacerda MV, Mourão MP, et al, “Successful Treatment of Plasmodium falciparum Malaria With a Six-Dose Regimen of Artemether-Lumefantrine Versus Quinine-Doxycycline in the Western Amazon Region of Brazil,” Am J Trop Med Hyg, 2006, 74(1):20-5. [PubMed 16407341]
  2. Ballard SB, Salinger A; MPHc, Arguin PM, Desai M, Tan KR. Updated CDC recommendations for using artemether-lumefantrine for the treatment of uncomplicated malaria in pregnant women in the United States. MMWR Morb Mortal Wkly Rep. 2018;67(14):424-431. doi: 10.15585/mmwr.mm6714a4. [PubMed 29649190]
  3. Centers for Disease Control and Prevention (CDC). CDC Yellow Book 2020: Health Information for International Travel. Oxford University Press; 2019.
  4. Centers for Disease Control and Prevention (CDC). Treatment of Malaria: Guidelines for Clinicians (United States). https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html. Updated May 29, 2020. Accessed June 8, 2020.
  5. Coartem (artemether and lumefantrine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2019.
  6. Makanga M, Premji Z, Falade C, et al, “Efficacy and Safety of the Six-Dose Regimen of Artemether-Lumefantrine in Pediatrics With Uncomplicated Plasmodium falciparum Malaria: a Pooled Analysis of Individual Patient Data,” Am J Trop Med Hyg, 2006, 74(6):991-8. [PubMed 16760509]
  7. McGready R, Tan SO, Ashley EA, et al, “A Randomised Controlled Trial of Artemether-Lumefantrine Versus Artesunate for Uncomplicated Plasmodium falciparum Treatment in Pregnancy,” PLoS Med, 2008, 5(12):e253. [PubMed 19265453]
  8. Omari AA, Gamble C, and Garner P, “Artemether-Lumefantrine (Six-Dose Regimen) for Treating Uncomplicated Falciparum Malaria,” Cochrane Database Syst Rev, 2005, Issue 4, Art. No.: CD005564. [PubMed 16235412]
  9. Toovey S and Jamieson A, “Audiometric Changes Associated With the Treatment of Uncomplicated Falciparum malaria With Co-Artemether,” Trans R Soc Trop Med Hyg, 2004, 98(5):261-7. [PubMed 15109547]
  10. “World Health Organization Guidelines for the Treatment of Malaria (2015),” Available at http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf
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