mefloquine in malaria prophylaxis

Last edited 12/2019

Summary: Mefloquine in malaria prophylaxis

  • acts as a suppressive prophylactic
  • an option for prophylaxis in areas where falciparum malaria highly resistant to chloroquine is seen e.g. East and Central Africa
  • adult dose is mefloquine 250mg per week " mefloquine should not be prescribed in the first trimester of pregnancy or for women who may become pregnant within 3 months of stopping the drug. It is contraindicated for patients with a history of a neuropsychiatric disorder, or convulsions, or family history of epilepsy. Also it is contraindicated during lactation, in patients under 2 years of age, or if there is a history of hypersensitivity to quinine"
  • over 75% of adverse reactions to mefloquine are apparent by the third dose (1). Therefore people who are to use mefloquine would be well advised to start taking it, particularly on the first occasion, three weeks before departure thus taking the third dose early enough to make a change if they encounter adverse reactions before leaving the UK
  • treatment should be continued throughout the stay and for four weeks after return (1)
  • in western Cambodia and mefloquine-resistant areas of Thailand, mefloquine is best avoided in favour of doxycycline or atovaquone/proguanil (1)

Mefloquine as chemoprophylaxis for malaria:

  • as with any antimalarial, stringent risk assessment is required before advising mefloquine use.

Mode of action

  • mefloquine's mode of action has not been determined but is thought to be unrelated to that of chloroquine and not to involve an anti-folate action. It acts as a suppressive prophylactic

Efficacy

  • protective efficacy of mefloquine is 90% or more. At the present time, significant resistance of P. falciparum to mefloquine is a problem only in some areas of south-East Asia, but is reported sporadically from the Amazon basin.

Prophylactic regimen

  • adult dose 250 mg weekly, starting 2 to 3 weeks before entering a malarious area to assess tolerability, continuing throughout the time in the area and for 4 weeks after leaving the area.

Contraindications

  • allergy to mefloquine or to any ingredient of the tablets

  • allergy to quinine or quinidine

  • a current or previous history of depression, generalized anxiety disorder, psychosis, schizophrenia, suicide attempts, suicidal thoughts, self-endangering behaviour or any other psychiatric disorder, epilepsy or convulsions of any origin. The risk of epilepsy and serious mental health disorders is higher in first degree relatives of those in whom these conditions have been diagnosed so they should be considered as part of risk assessment. A condition in a first-degree relative may not contraindicate the use of an antimalarial but may influence the choice of drug

  • a history of Blackwater fever

  • severe impairment of liver function

  • use with halofantrine; also, halofantrine should not be given within 15 weeks after the last dose of mefloquine

Cautions

  • pregnancy and breast-feeding; cardiac conduction disorders. Not recommended in infants under 5kg

  • SmPC points out that during clinical trials, mefloquine was not administered for longer than 1 year and states that periodic checks on liver function and eye assessments should be performed if mefloquine is used for a prolonged period. Any person taking mefloquine presenting with a visual disorder should be referred to their treating physician as this may require stopping chemoprophylaxis

  • in those who have suffered traumatic brain injury, the decision whether to advise mefloquine chemoprophylaxis should be made on an individual basis after a detailed risk assessment.

Interactions

  • drugs:
    • use with halofantrine is contraindicated
    • mefloquine antagonises the anticonvulsant effect of antiepileptics and may enhance the effect of other drugs that reduce the epileptogenic threshold, increasing the risk of convulsions
    • use of mefloquine with other drugs that affect cardiac conduction may enhance the risk of serious cardiac arrhythmias
    • mefloquine is metabolised in the liver by CYP3A4. Caution if administered with drugs that inhibit this enzyme due to increased mefloquine levels (for example itraconazole) . Drugs that induce metabolism of mefloquine may be expected to reduce mefloquine levels (for example rifampicin)
    • ritonavir levels are reduced by mefloquine due to decreased absorption, but the clinical significance of this interaction is unknown.

Side-effects

  • attention has focused on neuropsychiatric problems and vestibular disorders with mefloquine prophylaxis. Those taking mefloquine are more likely to have abnormal dreams, insomnia, anxiety and depressed mood during travel than those who take atovaquone-proguanil or doxycycline
  • increased neuropsychiatric adverse events have been found, especially in women using mefloquine, when compared with those receiving doxycycline, or atovaquone plus proguanil, but not those taking chloroquine plus proguanil. Mefloquine use may increase the risk of psychosis and anxiety reactions. No association between mefloquine prescriptions and hospitalisation has been demonstrated
  • dizziness, balance disorder, tinnitus and vertigo may occur. In a small number of patients, it has been reported that dizziness or vertigo and loss of balance may continue for months after discontinuing the drug
  • insomnian - in February 2018 the SmPC added insomnia to the list of psychiatric symptoms that must be regarded as prodromal for a more serious event. The updated list is insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion. Overall, mefloquine remains an important prophylactic agent which is tolerated by most travellers who take it

Roche have stated that (3):

  • Lariam (mefloquine) may induce potentially serious neuropsychiatric disorders

  • the most common neuropsychiatric reactions to mefloquine include abnormal dreams, insomnia, anxiety, and depression. Additionally hallucinations, psychosis, suicide, suicidal thoughts and self-endangering behaviour have been reported

  • do not use mefloquine for malaria chemoprophylaxis in patients with any active or a history of psychiatric disturbances

  • due to the long half-life of mefloquine, adverse reactions may occur and persist up to several months after discontinuation of the drug

  • healthcare professionals should react promptly to signs of neuropsychiatric reactions with mefloquine chemoprophylaxis. Mefloquine should be discontinued immediately and replaced by alternative malaria prophylaxis medication

  • advise patient that if they experience a neuropsychiatric reaction such as suicidal thoughts; self-endangering behaviour; severe anxiety; feelings of restlessness, confusion, or mistrust towards others; visual/auditory hallucinations; depression; or changes to their mental state during mefloquine chemoprophylaxis, they should stop taking mefloquine immediately and seek urgent medical advice

The summary of product characteristics must be consulted before prescribing this drug.

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