Lariam Side Effects, and Drug Interactions - Mefloquine

Lariam Side Effects, and Drug Interactions - Mefloquine

SIDE EFFECTS

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 Mefloquineuine 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 Mefloquineuine 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 Mefloquineuine while concomitantly using propranolol (see PRECAUTIONS: Drug Interactions ), and encephalopathy of unknown etiology during prophylactic Mefloquineuine 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 Mefloquineuine 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 Mefloquineuine, adverse reactions to Lariam may occur or persist up to several weeks after the last dose.

DRUG INTERACTIONS

Drug-drug interactions with Lariam have not been explored in detail. There is one report of cardiopulmonary arrest, with full recovery, in a patient who was taking a beta blocker (propranolol) (see PRECAUTIONS: General). The effects of Mefloquineuine on the compromised cardiovascular system have not been evaluated. The benefits of Lariam therapy should be weighed against the possibility of adverse effects in patients with cardiac disease.

Because of the danger of a potentially fatal prolongation of the QTc interval, halofantrine must not be given simultaneously with or subsequent to Lariam (see WARNINGS).

Concomitant administration of Lariam and other related compounds (eg, quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions (see WARNINGS). If these drugs are to be used in the initial treatment of severe malaria, Lariam administration should be delayed at least 12 hours after the last dose. There is evidence that the use of halofantrine after Mefloquineuine causes a significant lengthening of the QTc interval. Clinically significant QTc prolongation has not been found with Mefloquineuine alone.

This appears to be the only clinically relevant interaction of this kind with Lariam, although theoretically, coadministration of other drugs known to alter cardiac conduction (eg, anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H1-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. There are no data that conclusively establish whether the concomitant administration of Mefloquineuine and the above listed agents has an effect on cardiac function.

In patients taking an anticonvulsant (eg, valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of Lariam may reduce seizure control by lowering the plasma levels of the anticonvulsant. Therefore, patients concurrently taking antiseizure medication and Lariam should have the blood level of their antiseizure medication monitored and the dosage adjusted appropriately (see PRECAUTIONS: General).

When Lariam is taken concurrently with oral live typhoid vaccines, attenuation of immunization cannot be excluded. Vaccinations with attenuated live bacteria should therefore be completed at least 3 days before the first dose of Lariam.

No other drug interactions are known. Nevertheless, the effects of Lariam on travelers receiving comedication, particularly diabetics or patients using anticoagulants, should be checked before departure.

In clinical trials, the concomitant administration of sulfadoxine and pyrimethamine did not alter the adverse reaction profile.