Mefloquine

Also Known As: Mefloquine , Lariam, Mefloquine, Mefaquin

Mefloquine hydrochloride (also known as Lariam or Mefaquin) is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine. The brand name drug, Lariam, is manufactured by the Swiss company Hoffmann–La Roche. In August 2009, Roche stopped marketing Lariam in the United States. Generic mefloquine from other manufacturers, is still widely available. Rare but serious neuropsychiatric problems have been associated with its use.

Mefloquine is used to both prevent and treat certain forms of malaria.[1]

Malaria prevention

Mefloquine is useful for the prevention of malaria in all areas except for those where parasites may have resistance to multiple drugs.[2] It is typically taken for one to two weeks before entering an area with malaria.[1] Doxycycline and atovaquone/proguanil provide protection within one to two days and may be better tolerated.[3][4] If a person becomes ill with malaria despite prophylaxis with mefloquine the use of halofantrine and quinine for treatment may be ineffective.[5]

Malaria treatment

Once a person has contracted malaria, mefloquine is recommended as a second line treatment for chloroquine sensitive or resistant falciparum malaria and is deemed a reasonable alternative for uncomplicated chloroquine resistant vivax malaria.[1][5]

It is not recommended for severe malaria infections, particularly infections from P.falciparum which should be treated with intravenous antimalarials.[1][5] Mefloquine does not eliminate parasites in the liver phase of the disease, and people with P. vivax malaria should be treated with a second drug that is effective for the liver phase, such as primaquine.[6]


In pregnancy and breastfeeding

The World Health Organization gives approval for the use of mefloquine in the 2nd and 3rd trimester of pregnancy and use in the 1st trimester does not mandate termination of pregnancy.[2] Women should however not become pregnant and should use effective birth control while taking mefloquine.[7] It may be used during breastfeeding, though the drug appears in breast milk in low concentrations.[2][8]

Adverse effects

Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders.[1] Severe side effects requiring hospitalization are rare.[2] Rates of side effects appear similar to other medications used for malaria prevention.[3]

Neuropsychiatric

Neuropsychiatric effects are reported with mefloquine use.[1] The FDA product guide states it can cause mental health problems including: anxiety, hallucinations, depression, unusual behavior, and suicidal ideations among others.[7] Some have reported severe central nervous system events requiring hospitalization in about 1:10,000 people taking mefloquine for malaria prevention with milder events (e.g., dizziness, headache, insomnia, and vivid dreams) in up to 25%.[9] When some measure of subjective severity is applied to the rating of adverse events, about 11-17% of travelers are incapacitated to some degree.[3] In the Somalia Affair, some Members of Parliament and doctors postulated that this drug may have been a cause of the brutal beating death of Shidane Arone by Canadian Forces personnel, some of whom had been given experimental treatment using the drug. Dr. Michele Brill-Edwards resigned in protest from Health Canada over her belief that the drug could produce "dangerous psychiatric reactions" in the soldiers before the Somalia Affair took place.[requires citation]

Pneumonitis

The FDA has reported an association with pneumonitis and eosinophilic pneumonia[10]

Cardiac

Mefloquine may cause abnormalities with heart rhythms that are visible on electrocardiogram. Combining mefloquine with other drugs that cause similar effects, such as quinine or quinidine, can increase these effects. Combining mefloquine with halofantrine can cause significant increases in QTc interval.[11]

Mechanism of action

Mefloquine blocks the action of the chemical that the parasites produce to protect themselves once inside the red blood cells. There is increasing resistance to this drug, due to it being costly to produce, and to the fact that it may have serious adverse side effects in some recipients.

The exact mechanism of action is uncertain. However, it is proposed that it shares a similar mechanism of action with chloroquine, which is inhibition of heme polymerase.

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