FDA label 1aa2326b-8cca-5b52-e063-6394a90a82ac

WARNING Mefloquine may cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued. Mefloquine should not be prescribed for prophylaxis in patients with major psychiatric disorders. During prophylactic use, if psychiatric or neurologic symptoms occur, the drug should be discontinued and an alternative medication should be substituted (see WARNINGS ).

WARNINGS In case of life-threatening, serious or overwhelming malaria infections due to P. falciparum, patients should be treated with an intravenous antimalarial drug. Following completion of intravenous treatment, mefloquine may be given to complete the course of therapy. QTc Interval Prolongation and Drug Interactions Halofantrine should not be administered with mefloquine or within 15 weeks of the last dose of mefloquine due to the risk of a potentially fatal prolongation of the QTc interval (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Elimination ). Ketoconazole should not be administered with mefloquine or within 15 weeks of the last dose of mefloquine due to the risk of a potentially fatal prolongation of the QTc interval. Ketoconazole increases plasma concentrations and elimination half-life of mefloquine following coadministration (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Elimination and PRECAUTIONS, Drug Interactions ). Concomitant administration of mefloquine and quinine or quinidine may produce electrocardiographic abnormalities. Psychiatric and Neurologic Adverse Reactions Mefloquine may cause neuropsychiatric adverse reactions in adults and children. Neuropsychiatric symptoms can be difficult to identify in children. Therefore, vigilance is required to monitor for the occurrence of these symptoms, especially in nonverbal children. Psychiatric Adverse Reactions Psychiatric symptoms ranging from anxiety, paranoia, and depression to hallucinations and psychotic behavior can occur with mefloquine use. Symptoms may occur early in the course of mefloquine use. In some cases, these symptoms have been reported to continue for months or years after mefloquine has been stopped. Cases of suicidal ideation and suicide have been reported. Mefloquine should not be prescribed for prophylaxis in patients with active depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders. Mefloquine should be used with caution in patients with a previous history of depression. During prophylactic use, the occurrence of psychiatric symptoms such as acute anxiety, depression, restlessness or confusion suggest a risk for more serious psychiatric disturbances or neurologic adverse reactions. In these cases, the drug should be discontinued and an alternative medication should be substituted. Neurologic Adverse Reactions Neurologic symptoms such as dizziness or vertigo, tinnitus, and loss of balance have been reported. These adverse reactions may occur early in the course of mefloquine use and in some cases have been reported to continue for months or years after mefloquine has been stopped. Dizziness or vertigo, tinnitus, and loss of balance have been reported to be permanent in some cases. During prophylactic use, if neurologic symptoms occur, the drug should be discontinued and an alternative medication should be substituted. Caution should be exercised with regard to activities requiring alertness and fine motor coordination, such as driving, piloting aircraft, operating machinery, and deep-sea diving, while symptoms persist. Mefloquine may increase the risk of convulsions in patients with epilepsy. The drug should therefore be prescribed only for curative treatment in such patients and only if there are compelling medical reasons for its use (see PRECAUTIONS: Drug Interactions ). Concomitant administration of mefloquine and quinine or chloroquine may increase the risk of convulsions. Ocular Effects Eye disorders, including but not limited to optic neuropathy and retinal disorders, have been reported during treatment with mefloquine. Any patient presenting with visual symptoms should be referred to the treating physician and an ophthalmologist as certain conditions (such as retinal disorders or optic neuropathy) may require stopping treatment with mefloquine (see PRECAUTIONS , ANIMAL TOXICOLOGY ).

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. 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. 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. 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 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 discontinuation of the drug. Postmarketing Postmarketing surveillance indicates that the same kind of adverse reactions are reported during prophylaxis, as well as acute treatment. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to mefloquine exposure. The most frequently reported adverse reactions 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 adverse reactions may occur early in the course of mefloquine use. It has been reported that dizziness or vertigo, tinnitus and hearing impairment, and loss of balance may continue for months or years after discontinuation of the drug and may be permanent in some cases. 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 swings, panic attacks, memory impairment, confusion, hallucinations, aggression, psychotic or paranoid reactions and encephalopathy. Cases of suicidal ideation and suicide have been reported. Other less frequently reported adverse reactions include: Cardiovascular Disorders: circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitation, bradycardia, irregular heart rate, 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. Respiratory Disorders: dyspnea, pneumonitis of possible allergic etiology. Hepatobiliary Disorders: drug-related hepatic disorders from asymptomatic transient transaminase elevations to hepatic failure. Blood and Lymphatic System Disorders: agranulocytosis, aplastic anemia. Ocular Disorders: visual impairment, vision blurred, cataracts, retinal disorders, optic neuropathy. Other Symptoms: asthenia, malaise, fatigue, fever, hyperhidrosis, chills, dyspepsia and loss of appetite.