The current labeling for the antimalarial mefloquine is inconsistent internationally with medication guides regarding certain adverse reactions, including depression and anxiety, according to a review of drug labels and medication guides from six English-speaking countries.
Neuropsychiatric reactions have been reported by 29% to 77% of mefloquine users at prophylactic doses of 250 mg per week, wrote Remington L. Nevin, MD, MPH, of Johns Hopkins University in Baltimore, and Aricia M. Byrd, an MD student at Trinity School of Medicine, Kingstown, St. Vincent and the Grenadines. “Neuropsychiatric adverse reactions may occur early during use – frequently within the first three doses – and may even occur after only a single dose,” the researchers said (Neurol Ther. 2016 Jun;5[1]:69-83).
In addition, data suggest that the neuropsychiatric adverse reactions, including nightmares and cognitive dysfunction, can last many years after the drug has been discontinued, and a black box warning was added to the U.S. label in 2013 to emphasize the potential long-term impact, Dr. Nevin and Ms. Byrd reported.
In this study, Dr. Nevin and Ms. Byrd compared prescribing information and patient safety guidance in the United States and five other English-speaking countries: the United Kingdom, Ireland, Australia, Canada, and New Zealand.
At the time of the study, mefloquine was licensed in all six countries, but the innovator product was withdrawn from the United States in 2011 and from Canada in 2013.
In addition to the United States, the United Kingdom and Ireland recommended discontinuing mefloquine at the onset of any general neurologic or psychiatric symptoms, the researchers noted.
All six countries were in complete agreement with corresponding medication guides and drug labeling that recommended discontinuing mefloquine or consulting a healthcare provider if adverse reactions occurred within four high level group terms (HLGTs): anxiety disorders and symptoms, changes in physical activity, depressed mood disorders and disturbances, and deliria (including confusion).
Three of the six countries (the United States, the United Kingdom, and Ireland) show partial agreement in medication guides and drug labeling recommendations to discontinue the drug or consult a healthcare provider in the instance of three other HLGTs: disturbances in thinking and perception, personality disorders and disturbances in behavior, and suicidal and self-injurious behaviors not elsewhere classified. The United Kingdom and Ireland also showed partial agreement in corresponding medication guides and drug labeling, drug discontinuation, or consulting a healthcare provider for the following adverse reactions: neuromuscular disorders, sleep disorders and disturbances, and peripheral neuropathies.
In the United States alone, medication guides and drug labeling corresponded in terms of drug discontinuation or healthcare provider consultation in cases of cranial nerve disorders, excluding neoplasms and neurologic disorders not elsewhere classified. For nine other areas of adverse reactions, medication guidelines recommended healthcare provider consultation, but no corresponding guidance was found on the drug labeling.
The review was limited by several factors, including the use of data from only six countries and the subjective interpretation of the language used in the drug labeling and medication guides, the researchers noted.
However, the results “suggest opportunities for physicians in these countries to improve patient counseling by specifically emphasizing the need to discontinue at the onset of these adverse reactions,” they said.
“The results of this analysis also suggest opportunities for international drug regulators to clarify language in future updates to remaining mefloquine drug labels and medication guides to better reflect national risk-benefit considerations for continued use of the drug,” they concluded.
Dr. Nevin disclosed that he has been retained as consultant and expert witness in legal cases involving antimalarial drug toxicity claims. Ms. Byrd had no financial conflicts to disclose.