Drug Class Description
4-Aminoquinolones (aminoquinolones, antimalarials).

Generic Name
Mefloquine

Drug Description
Each tablet contains 250mg mefloquine (as 274.09mg mefloquine hydrochloride).

Presentation
Tablet. White to off-white cylindrical biplanar tablets, cross scored and imprinted with Roche on one face.

Indications
Therapy and prophylaxis of malaria.Therapy: Lariam is especially indicated for therapy of P. falciparum malaria in which the pathogen has become resistant to other antimalarial agents.Following treatment of P. vivax malaria with Lariam, relapse prophylaxis with an 8-amino-quinoline derivative, for example primaquine, should be considered in order to eliminate parasites in the hepatic phase. Prophylaxis: Malaria prophylaxis with Lariam is particularly recommended for travellers to malarious areas in which multiple resistant P. falciparum strains occur.For current advice on geographical resistance patterns and appropriate chemoprophylaxis, current guidelines or the Malaria Reference Laboratory should be consulted, details of which can be found in the British National Formulary (BNF).

Adult Dosage
Curative treatmentThe recommended total therapeutic dose of mefloquine for non-immune patients is 20 – 25mg/kg. A lower total dose of 15mg/kg may suffice for partially immune individuals.The recommended total therapeutic dosages of Lariam tablets relative to body weight and immune status are presented in the following table.*Non-immune patientsPartially immune patients< 20kg **¼ tablet / 2.5 – 3kg 1 tablet / 10 – 12 kg¼ tablet / 4kg 1 tablet / 16kg20 – 30kg2 – 3 tablets1¼– 2 tablets> 30 – 45kg3 – 4 tablets2 – 3 tablets> 45 – 60kg4 – 5 tablets3 – 4 tablets> 60kg ***6 tablets4 – 6 tablets*Splitting the total curative dosage into 2 – 3 doses (e.g. 3 + 1, 3 + 2 or 3 + 2 + 1 tablets) taken 6 – 8 hours apart may reduce the occurrence or severity of adverse events.**Experience with Lariam in infants less than 3 months old or weighing less than 5kg is limited.***There is no specific experience with total dosages of more than 6 tablets in very heavy patients.A second full dose should be given to patients who vomit less than 30 minutes after receiving the drug. If vomiting occurs 30 – 60 minutes after a dose, an additional half-dose should be given.If a full treatment course with Lariam does not lead to improvement within 48 – 72 hours, alternative treatments should be considered. When breakthrough malaria occurs during Lariam prophylaxis, physicians should carefully eva luate which antimalarial to use for therapy.Lariam can be given for severe acute malaria after an initial course of intravenous quinine lasting at least 2 – 3 days. Interactions leading to adverse events can largely be prevented by allowing an interval of at least 12 hours after the last dose of quinine.In areas with multi-resistant malaria, initial treatment with artemisinin or a derivative, if available, followed by Lariam is also an option.Malaria prophylaxisFor malaria prophylaxis the stated dose of Lariam should be given once weekly, always on the same day. Treatment should be initiated at least one week and up to 2-3 weeks before arrival in a malarious area and continued for 4 weeks after leaving (minimum treatment period 6 weeks). The maximum recommended duration of administration of Lariam is 12 months.The following dosage schedule is given as a guide.DosageAdults and children of more than 45kg bodyweight1 tabletChildren and adults weighing less than 45kg5 – 19kg¼ tablet20 – 30kg½ tablet31 – 45kg¾ tabletThe tablets should be swallowed whole preferably after a meal with plenty of liquid.ElderlyNo specific adaptation of the usual adult dosage is required for elderly patients.

Child Dosage
Prophylaxis, under 5 kg, not recommended; 5 - 19 kg, / tablet; 20 - 30 kg, / tablet; 31 - 45 kg, three quarters of a tablet; over 45 kg, 1 tablet. The dose should be taken once weekly after a meal on the same day for minimum 6 weeks, starting at least 1 week and up to 2 - 3 weeks before departure and continuing for 4 weeks on return. Maximum period of prophylaxis, 12 months. Treatment, see data sheet.

Contra Indications
Prophylactic use in patients with severe impairment of liver function should be regarded for the time being as a contraindication as no experience has been gained in such patients.Patients with a history of psychiatric disturbances (including depression) or convulsions should not be prescribed Lariam prophylactically, as it may precipitate these conditions.Lariam should not be administered to patients with a known hypersensitivity to mefloquine or related compounds, e.g. quinine.Because of the danger of a potentially fatal prolongation of the QTc interval, halofantrine must not be given simultaneously with or subsequent to Lariam. No data are available where Lariam was given after halofantrine.

Special Precautions
Women of childbearing potential travelling to malarious areas in which multiple resistant P. falciparum is found and who are receiving Lariam for the treatment and prophylaxis of malaria should take reliable contraceptive precautions for the entire duration of therapy and for three months after the last dose of Lariam.If psychiatric disturbances occur during prophylactic use, Lariam should be discontinued and an alternative prophylactic agent should be recommended.Experience with Lariam in infants less than 3 months old or weighing less than 5kg is limited.There is no evidence that dose adjustment is necessary for patients with renal insufficiency. However, since clinical evidence in such patients is limited, caution should be exercised when using Lariam in patients with impaired renal function.In patients with epilepsy, mefloquine may increase the risk of convulsions. Therefore in such cases, Lariam should be used only for curative treatment and only if compelling reasons exist.Lariam should be taken with caution in patients suffering from cardiac conduction disorders, since transient cardiac conduction alterations have been observed during curative and preventative use.Patients should not disregard the possibility that re-infection or recrudescence may occur after effective antimalarial therapy.Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Interactions
Concomitant administration of Lariam and other related compounds (e.g. quinine, quinidine and chloroquine) may produce electrocardiographic abnormalities and increase the risk of convulsions. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Clinically significant QTc prolongation has not been found with mefloquine alone.This appears to be the only clinically relevant interaction of this kind with Lariam, although theoretically co-administration of other drugs known to alter cardiac conduction (e.g. anti-arrhythmic or βadrenergic blocking agents, calcium channel blockers, antihistamines or H1-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval.In patients taking an anticonvulsant (e.g. valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of Lariam may reduce seizure control by lowering the plasma levels of the anticonvulsant. Dosage adjustments of anti-seizure medication may be necessary in some cases.When Lariam is taken concurrently with oral live typhoid vaccines, attenuation of immunisation cannot be excluded. Vaccinations with oral 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 travellers receiving comedication, particularly those on anticoagulants or antidiabetics, should be checked before departure.

Adverse Reactions
At the doses given for acute malaria, adverse reactions to Lariam may not be distinguishable from symptoms of the disease itself. The overall incidence of adverse events reported during mefloquine prophylaxis is comparable to that reported for other chemoprophylactic regimens. However, the profile of mefloquine adverse events is predominantly characterised by neuropsychological adverse events. Because of the long half-life of mefloquine, adverse reactions to Lariam may occur or persist for more than several weeks after the last dose.Patients should be advised to obtain medical advice before the next weekly dose of Lariam, if any concerning or neuropsychiatric symptoms develop. Discontinuation of Lariam should be considered, particularly if neuropsychiatric reactions occur. The need for alternative antimalarial therapy or prophylaxis can then be eva luated.Common adverse reactionsNausea, vomiting, dizziness or vertigo, loss of balance, headache, somnolence, sleep disorders (insomnia, abnormal dreams), loose stools or diarrhoea and abdominal pain.Uncommon adverse reactionsPsychiatric: Psychiatric reactions sometimes disabling and prolonged have been reported in association with Lariam. These include depression, mood changes, anxiety, confusion, hallucinations, panic attacks, restlessness, forgetfulness, psychosis and paranoia, emotional instability, aggression and agitation. There have been rare reports of suicidal ideation and suicide but no relationship to drug administration has been established.Neurological: Convulsions, sensory and motor neuropathies (including paraesthesia), tremor, tinnitus and vestibular disorders, including hearing impairment, abnormal co-ordination, ataxia and visual disturbances.Cardiovascular system: Circulatory disturbances (hypotension, hypertension, flushing, syncope), chest pain, tachycardia or palpitations, bradycardia, irregular pulse, extrasystoles and other transient cardiac conduction alterations.Skin: Rash, exanthema, erythema, urticaria, pruritus, oedema, hair loss, erythema multiforme, Stevens-Johnson syndrome.Musculo-skeletal system: Muscle weakness and muscle cramps, myalgia, arthralgia.Respiratory system: Dyspnoea. Very rare cases of pneumonitis of possible allergic aetiology have been reported.General symptoms: Asthenia, malaise, fatigue, fever, sweating, chills, loss of appetite and dyspepsia.Haematological: Leucopenia or leucocystosis, thrombocytopenia.Laboratory abnormalities: Transient elevation of transaminases.Very rare adverse reactions: AV-block and encephalopathy. There have also been rare reports of anaphylaxis in patients taking Lariam.Studies in vitro and in vivo showed no haemolysis associated with G6PD deficiency.

Manufacturer
Roche

Drug Availability
(POM)

Updated
23 June 2009