Mefloquine is a quinoline derivative used for the prevention and therapy of P. falciparum malaria. Mefloquine therapy is associated with a low rate of transient and asymptomatic serum enzyme elevations and is a rare cause of clinically apparent acute liver injury.


Mefloquine (mef' loe kwin) is a quinoline methanol similar to quinine and is active against the asexual stages of malaria. Its exact mechanism of activity is unknown. Mefloquine is effective as prophylaxis against malaria and is widely used in therapy against chloroquine-resistant P. falciparum infection. Unfortunately, mefloquine resistance is becoming an enlarging problem. Mefloquine was approved for use in the United States in 1989 and is available in tablets of 250 mg in several generic forms and under the brand name Lariam. The recommended dosage for suppressive prophylaxis is 250 mg once weekly for 1 week before to 4 weeks after travel to an endemic area. Specific recommendations on the therapy of malaria including details on diagnosis, drug dosage and safety are available at the CDC website: http://www.cdc.gov/malaria/. Common side effects of mefloquine include headache, fatigue, insomnia, vivid dreams, anorexia, nausea, diarrhea, abdominal discomfort, dizziness, rash and pruritus. Rare side effects include hallucinations, disorientation and seizures.


Chronic therapy with mefloquine is associated with asymptomatic, transient serum enzyme elevations in up to 18% of patients. These elevations are usually mild and resolve without dose modifications. Despite widespread use, mefloquine has rarely been linked to clinically apparent acute liver injury and too few reports are available to characterize the clinical features of such injury. Instances of acute hepatocellular injury as well as cholestatic hepatitis have been linked to use of mefloquine. Allergic manifestations (rash, fever, eosinophilia) and autoantibody formation are rare.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

Mechanism of Injury

The cause of the hepatic injury from mefloquine is unknown, but may relate to a metabolic intermediate with direct toxicity or ability to induce an immune mediated hepatotoxicity. Mefloquine undergoes extensive hepatic metabolism to an inactive metabolite that is excreted in the urine.

Outcome and Management

There does not seem to be cross reactivity to hepatic injury among the various antimalarial agents and switching to other drug can be done.

Drug Class: Antimalarial Agents


Case 1. Acute hepatitis due to mefloquine prophylaxis of malaria.

[Modified from: Bruguera M, Herrera S. [Acute hepatitis associated with mefloquine therapy]. Gastroenterol Hepatol 2007; 30: 102-3. Spanish. PubMed Citation]

A 35 year old woman working in health care in Liberia developed nausea, poor appetite and pruritus 2 months after starting malarial prophylaxis with mefloquine (250 mg weekly). She had no history of liver disease, alcohol abuse or risk factors for viral hepatitis. She denied fever. On examination, she was jaundiced and had a desquamating erythematous rash over the hands and palms. She had stopped the mefloquine when she first began to feel ill. Laboratory testing showed marked elevations in serum aminotransferase and alkaline phosphatase levels (Table) with a total serum bilirubin of 7.1 mg/dL. The prothombin time was normal. Tests for hepatitis A, B and C were negative. Ultrasound of the abdomen showed no evidence of biliary obstruction. Over the next few days she began to improve. In follow up 5 weeks later, serum liver tests had returned to near normal levels.

Key Points

Laboratory Values


Despite the frequency of serum aminotransferase elevations during mefloquine therapy, there have been few reports of clinically apparent liver disease with jaundice. The current report described a self limited acute hepatitis-like syndrome arising 2 months after starting a prophylactic regimen of mefloquine. Although the height of the serum aminotransferase levels were indicative of a hepatocellular pattern of injury, the high alkaline phosphatase levels and early presentation with pruritus suggests that the hepatic injury was at least partially cholestatic. This “mixed” pattern is typical of drug induced liver injury.



Mefloquine – Generic, Lariam®


Antimalarial Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 07 February 2017

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