Adverse effects of Mefloquine for the treatment of uncomplicated malaria in Thailand

A pooled analysis of 19, 850 individual patients

Sue J. Lee, Feiko O. Ter Kuile, Ric N. Price, Christine Luxemburger, François Nosten

    Research output: Contribution to journalArticleResearchpeer-review

    4 Downloads (Pure)

    Abstract

    Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

    Original languageEnglish
    Article number0168780
    Pages (from-to)1-16
    Number of pages16
    JournalPLoS One
    Volume12
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2017

    Fingerprint

    Mefloquine
    Thailand
    malaria
    Malaria
    adverse effects
    dosage
    Therapeutics
    sulfadoxine
    pyrimethamine
    Cambodia
    Myanmar
    multiple drug resistance
    South East Asia
    signs and symptoms (animals and humans)
    confidence interval
    Far East
    Falciparum Malaria
    Multiple Drug Resistance
    therapeutics

    Cite this

    Lee, Sue J. ; Ter Kuile, Feiko O. ; Price, Ric N. ; Luxemburger, Christine ; Nosten, François. / Adverse effects of Mefloquine for the treatment of uncomplicated malaria in Thailand : A pooled analysis of 19, 850 individual patients. In: PLoS One. 2017 ; Vol. 12, No. 2. pp. 1-16.
    @article{f806c28a39f74016a3913dcef0383a59,
    title = "Adverse effects of Mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients",
    abstract = "Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95{\%} confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95{\%} CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.",
    author = "Lee, {Sue J.} and {Ter Kuile}, {Feiko O.} and Price, {Ric N.} and Christine Luxemburger and Fran{\cc}ois Nosten",
    year = "2017",
    month = "2",
    day = "1",
    doi = "10.1371/journal.pone.0168780",
    language = "English",
    volume = "12",
    pages = "1--16",
    journal = "PLoS One",
    issn = "1932-6203",
    publisher = "Public Library of Science (PLoS)",
    number = "2",

    }

    Adverse effects of Mefloquine for the treatment of uncomplicated malaria in Thailand : A pooled analysis of 19, 850 individual patients. / Lee, Sue J.; Ter Kuile, Feiko O.; Price, Ric N.; Luxemburger, Christine; Nosten, François.

    In: PLoS One, Vol. 12, No. 2, 0168780, 01.02.2017, p. 1-16.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Adverse effects of Mefloquine for the treatment of uncomplicated malaria in Thailand

    T2 - A pooled analysis of 19, 850 individual patients

    AU - Lee, Sue J.

    AU - Ter Kuile, Feiko O.

    AU - Price, Ric N.

    AU - Luxemburger, Christine

    AU - Nosten, François

    PY - 2017/2/1

    Y1 - 2017/2/1

    N2 - Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

    AB - Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

    UR - http://www.scopus.com/inward/record.url?scp=85012165837&partnerID=8YFLogxK

    U2 - 10.1371/journal.pone.0168780

    DO - 10.1371/journal.pone.0168780

    M3 - Article

    VL - 12

    SP - 1

    EP - 16

    JO - PLoS One

    JF - PLoS One

    SN - 1932-6203

    IS - 2

    M1 - 0168780

    ER -