Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1794
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Lariam (Tablet)
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Adult Patients: Treatment of mild to moderate malaria in adults caused
by P. vivax or mefloquine-susceptible
strains of P. falciparum Five tablets (1250 mg) mefloquine hydrochloride to be
given as a single oral dose. The drug should not be taken on an empty
stomach and should be administered with at least 8 oz (240 mL) of
water. If a full-treatment course with Lariam
does not lead to improvement within 48 to 72 hours, Lariam should
not be used for retreatment. An alternative therapy should be used.
Similarly, if previous prophylaxis with mefloquine has failed, Lariam
should not be used for curative treatment.<br/>Malaria Prophylaxis: One 250 mg Lariam tablet once weekly. Prophylactic drug administration should begin 1 week before
arrival in an endemic area. Subsequent weekly doses should be taken
regularly, always on the same day of each week, preferably after the
main meal. To reduce the risk of malaria after leaving an endemic
area, prophylaxis must be continued for 4 additional weeks to ensure
suppressive blood levels of the drug when merozoites emerge from the
liver. Tablets should not be taken on an empty stomach and should
be administered with at least 8 oz (240 mL) of water. In certain cases, eg, when a traveler is taking other medication,
it may be desirable to start prophylaxis 2 to 3 weeks prior to departure,
in order to ensure that the combination of drugs is well tolerated
(see PRECAUTIONS:
Drug Interactions). When
prophylaxis with Lariam fails, physicians should carefully evaluate
which antimalarial to use for therapy.<br/>Pediatric Patients: Treatment of mild to moderate malaria in pediatric
patients caused by mefloquine-susceptible strains of P. falciparum Twenty (20) to 25 mg/kg body weight. Splitting the total therapeutic
dose into 2 doses taken 6 to 8 hours apart may reduce the occurrence
or severity of adverse effects. Experience with Lariam in infants
less than 3 months old or weighing less than 5 kg is limited. The
drug should not be taken on an empty stomach and should be administered
with ample water. The tablets may be crushed and suspended in a small
amount of water, milk or other beverage for administration to small
children and other persons unable to swallow them whole. If a full-treatment course with Lariam does not lead to
improvement within 48 to 72 hours, Lariam should not be used for retreatment.
An alternative therapy should be used. Similarly, if previous prophylaxis
with mefloquine has failed, Lariam should not be used for curative
treatment. In pediatric patients, the administration
of Lariam for the treatment of malaria has been associated with early
vomiting. In some cases, early vomiting has been cited as a possible
cause of treatment failure . If a significant
loss of drug product is observed or suspected because of vomiting,
a second full dose of Lariam should be administered to patients who
vomit less than 30 minutes after receiving the drug. If vomiting occurs
30to 60 minutes after a dose, an additional half-dose should be given.
If vomiting recurs, the patient should be monitored closely and alternative
malaria treatment considered if improvement is not observed within
a reasonable period of time. The safety and
effectiveness of Lariam to treat malaria in pediatric patients below
the age of 6 months have not been established.<br/>Malaria Prophylaxis: The following doses have been extrapolated from the
recommended adult dose. Neither the pharmacokinetics, nor the clinical
efficacy of these doses have been determined in children owing to
the difficulty of acquiring this information in pediatric subjects.
The recommended prophylactic dose of Lariam is approximately 5 mg/kg
body weight once weekly. One 250 mg Lariam tablet should be taken
once weekly in pediatric patients weighing over 45 kg. In pediatric
patients weighing less than 45 kg, the weekly dose decreases in proportion
to body weight: 30
to 45 kg: 3/4 tablet 20 to 30 kg: 1/2
tablet 10 to 20
kg: 1/4 tablet 5 to 10 kg: 1/8
tablet Experience with Lariam in infants less than 3 months old
or weighing less than 5 kg is limited.
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| dailymed-instance:descripti... |
Lariam (mefloquine hydrochloride) is an antimalarial
agent available as 250-mg tablets of mefloquine hydrochloride (equivalent
to 228.0 mg of the free base) for oral administration. Mefloquine hydrochloride is a 4-quinolinemethanol derivative
with the specific chemical name of (R*, S*)-(��)-��-2-piperidinyl-2,8-bis
(trifluoromethyl)-4-quinolinemethanol hydrochloride. It is a 2-aryl
substituted chemical structural analog of quinine. The drug is a white
to almost white crystalline compound, slightly soluble in water. Mefloquine hydrochloride has a calculated molecular weight
of 414.78 and the following structural formula: The inactive
ingredients are ammonium-calcium alginate, corn starch, crospovidone,
lactose, magnesium stearate, microcrystalline cellulose, poloxamer
#331, and talc.
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Pharmacokinetics:<br/>Absorption: The absolute oral bioavailability of mefloquine has
not been determined since an intravenous formulation is not available.
The bioavailability of the tablet formation compared with an oral
solution was over 85%. The presence of food significantly enhances
the rate and extent of absorption, leading to about a 40% increase
in bioavailability. In healthy volunteers, plasma concentrations peak
6 to 24 hours (median, about 17 hours) after a single dose of Lariam.
In a similar group of volunteers, maximum plasma concentrations in��g/L
are roughly equivalent to the dose in milligrams (for example, a single
1000 mg dose produces a maximum concentration of about 1000��g/L).
In healthy volunteers, a dose of 250 mg once weekly produces maximum
steady-state plasma concentrations of 1000 to 2000��g/L, which
are reached after 7 to 10 weeks.<br/>Distribution: In healthy adults, the apparent volume of distribution
is approximately 20 L/kg, indicating extensive tissue distribution.
Mefloquine may accumulate in parasitized erythrocytes. Experiments
conducted in vitro with human blood using concentrations between 50
and 1000 mg/mL showed a relatively constant erythrocyte-to-plasma
concentration ratioof about 2 to 1. The equilibrium reached in less
than 30 minutes was found to be reversible. Protein binding is about
98%. Mefloquine crosses the placenta. Excretion
into breast milk appears to be minimal .<br/>Metabolism: Two metabolites have been identified in humans. The
main metabolite, 2,8-bis-trifluoromethyl-4-quinoline
carboxylic acid, is inactive in Plasmodium
falciparum. In a study in healthy volunteers, the carboxylic
acid metabolite appeared in plasma 2 to 4 hours after a single oral
dose. Maximum plasma concentrations, which were about 50% higher than
those of mefloquine, were reached after 2 weeks. Thereafter, plasma
levels of the main metabolite and mefloquine declined at a similar
rate. The area under the plasma concentration-time curve (AUC) of
the main metabolite was 3 to 5 times larger than that of the parent
drug. The other metabolite, an alcohol, was present in minute quantities
only.<br/>Elimination: In several studies in healthy adults, the mean elimination
half-life of mefloquine varied between 2 and 4 weeks, with an average
of about 3 weeks. Total clearance, which is essentially hepatic, is
in the order of 30 mL/min. There is evidence that mefloquine is excreted
mainly in the bile and feces. In volunteers, urinary excretion of
unchanged mefloquine and its main metabolite under steady-state condition
accounted for about 9% and 4% of the dose, respectively. Concentrations
of other metabolites could not be measured in the urine.<br/>Pharmacokinetics in Special
Clinical Situations:<br/>Microbiology:<br/>Mechanism of Action: Mefloquine is an antimalarial agent which acts as
a blood schizonticide. Its exact mechanism of action is not known.<br/>Activity In Vitro and In Vivo: Mefloquine is active against the erythrocytic stages
of Plasmodium species . However, the drug has no effect against the exoerythrocytic
(hepatic) stages of the parasite. Mefloquine is effective against
malaria parasites resistant to chloroquine .<br/>Drug Resistance: Strains of P. falciparum with decreased susceptibility to mefloquine can be selected in vitro
or in vivo. Resistance of P. falciparum to mefloquine has been reported in areas of multi-drug resistance
in South East Asia. Increased incidences of resistance have also been
reported in other parts of the world.<br/>Cross-Resistance: Cross-resistance between mefloquine
and halofantrine and cross-resistance between mefloquine and quinine
have been observed in some regions.
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Use of Lariam is contraindicated in patients with
a known hypersensitivity to mefloquine or related compounds (eg, quinine
and quinidine) or to any of the excipients contained in the formulation.
Lariam should not be prescribed for prophylaxis in patients with active
depression, a recent history of depression, generalized anxiety disorder,
psychosis, or schizophrenia or other major psychiatric disorders,
or with a history of convulsions.
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Lariam is available as scored, white, round tablets,
containing 250 mg of mefloquine hydrochloride in unit-dose packages
of 25 (NDC 0004-0172-02). Imprint on tablets: LARIAM 250 ROCHE Tablets should be stored at 25��C (77��F); excursions
permitted to 15��to 30��C (59��to 86��F).
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Symptoms and Signs: In cases of overdosage with Lariam, the symptoms
mentioned under ADVERSE REACTIONS may be more pronounced.<br/>Treatment: Patients should be managed by symptomatic and supportive
care following Lariam overdose. There are no specific antidotes. Monitor
cardiac function (if possible by ECG) and neuropsychiatric status
for at least 24 hours. Provide symptomatic and intensive supportive
treatment as required, particularly for cardiovascular disturbances.
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mefloquine hydrochloride
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Lariam (Tablet)
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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 , and encephalopathy
of unknown etiology during prophylactic mefloquine administration.
The relationship of encephalopathy to drug administration could not
be clearly established.<br/>Postmarketing: Postmarketing surveillance indicates that the same
kind of adverse experiences are reported during prophylaxis, as well
as acute treatment. Because these experiences 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 Lariam exposure. 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. In a small number of patients it has been reported
that dizziness or vertigo and loss of balance may continue for months
after discontinuation of the drug. 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 Respiratory Disorders: dyspnea, pneumonitis of possible allergic etiology Other Symptoms: visual disturbances,
vestibular disorders including tinnitus and hearing impairment, asthenia,
malaise, fatigue, fever, sweating, chills, dyspepsia and loss of appetite<br/>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 Lariam may occur or persist up to several weeks after the last
dose.
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Treatment of Acute Malaria
Infections: Lariam is indicated for the treatment of mild to
moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible
and resistant strains) or by Plasmodium
vivax. There are insufficient clinical data to document
the effect of mefloquine in malaria caused by P. ovale or P. malariae.<br/>Prevention of Malaria: Lariam is indicated for the prophylaxis of P. falciparum and P. vivax malaria infections, including
prophylaxis of chloroquine-resistant strains of P. falciparum.
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Lariam
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