Adverse Reactions:

Clinical:

At the doses used for treatment of acute malaria infections, the symptoms possibly attributable to drug administration cannot be distinguished from those symptoms usually attributable to the disease itself.

Among subjects who received mefloquine for prophylaxis of malaria, the most frequently observed adverse experience was vomiting (3%). Dizziness, syncope, extrasystoles and other complaints affecting less than 1% were also reported.

Among subjects who received mefloquine for treatment, the most frequently observed adverse experiences included: dizziness, myalgia, nausea, fever, headache, vomiting, chills, diarrhea, skin rash, abdominal pain, fatigue, loss of appetite, and tinnitus. Those side effects occurring in less than 1% included bradycardia, hair loss, emotional problems, pruritus, asthenia, transient emotional disturbances and telogen effluvium (loss of resting hair). Seizures have also been reported.

Two serious adverse reactions were cardiopulmonary arrest in one patient shortly after ingesting a single prophylactic dose of mefloquine while concomitantly using propranolol (see PRECAUTIONS: Drug Interactions), and encephalopathy of unknown etiology during prophylactic mefloquine administration. The relationship of encephalopathy to drug administration could not be clearly established.

Postmarketing:

Postmarketing surveillance indicates that the same kind of adverse experiences are reported during prophylaxis, as well as acute treatment.

The most frequently reported adverse events are nausea, vomiting, loose stools or diarrhea, abdominal pain, dizziness or vertigo, loss of balance, and neuropsychiatric events such as headache, somnolence, and sleep disorders (insomnia, abnormal dreams). These are usually mild and may decrease despite continued use.

Occasionally, more severe neuropsychiatric disorders have been reported such as: sensory and motor neuropathies (including paresthesia, tremor and ataxia), convulsions, agitation or restlessness, anxiety, depression, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, psychotic or paranoid reactions and encephalopathy. Rare cases of suicidal ideation and suicide have been reported though no relationship to drug administration has been confirmed.

Other infrequent adverse events include:

Cardiovascular Disorders:

circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitation, bradycardia, irregular pulse, extrasystoles, A-V block, and other transient cardiac conduction alterations.

Skin Disorders:

rash, exanthema, erythema, urticaria, pruritus, edema, hair loss, erythema multiforme, and Stevens-Johnson syndrome.

Musculoskeletal Disorders:

muscle weakness, muscle cramps, myalgia, and arthralgia.

Other Symptoms:

visual disturbances, vestibular disorders including tinnitus and hearing impairment, dyspnea, asthenia, malaise, fatigue, fever, sweating, chills, dyspepsia and loss of appetite.

Laboratory:

The most frequently observed laboratory alterations which could be possibly attributable to drug administration were decreased hematocrit, transient elevation of transaminases, leukopenia and thrombocytopenia. These alterations were observed in patients with acute malaria who received treatment doses of the drug and were attributed to the disease itself.

During prophylactic administration of mefloquine to indigenous populations in malaria-endemic areas, the following occasional alterations in laboratory values were observed: transient elevation of transaminases, leukocytosis or thrombocytopenia.

Because of the long half-life of mefloquine, adverse reactions to mefloquine may occur or persist up to several weeks after the last dose.