INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo MEFLIAM TABLETS

SCHEDULING STATUS
Schedule 4

PROPRIETARY NAME
(and dosage form):

MEFLIAM TABLETS

COMPOSITION
Each tablet contains
mefloquine hydrochloride 274 mg equivalent to mefloquine 250 mg.

PHARMACOLOGICAL CLASSIFICATION:
A: 20.2.6 Medicines against protozoa

PHARMACOLOGICAL ACTION:
Mefloquine is a quinoline methanol derivative, structurally related to quinine. Mefloquine is a blood schizontozide with effects on the asexual blood forms of the malarial pathogens that affect humans (Plasmodium falciparum, P. vivax). It is also active against the gametocytes of P. vivax. Its mechanism of action is unknown. Mefloquine has no effect on the hepatic stage of malaria parasites. Strains of P. falciparum resistant to mefloquine have been reported.
Cross-resistance between halofantrine and mefloquine has been observed. Resistance to mefloquine as well as to any other antimalarial may occur in any endemic area. Mefloquine resistance has been described. Resistance patterns occur and vary from region to region and with time.
Pharmacokinetics: The maximum plasma concentration after a single oral dose is reached in 6 to 24 hours (average 17 hours). The achieved plasma concentration in nanograms per millilitre is roughly equivalent to the dose in milligrams. In steady state with weekly doses of 250 mg, maximum plasma concentration of 1 000 ng/mL have been recorded. Mefloquine is 98% bound to plasma proteins. Mefloquine has a large apparent volume of distribution (13,5-29,1 L/kg). The main metabolite of mefloquine, 2,8-bistrifluoromethyl-4-quinoline carboxylic acid, is inactive against P. falciparum. It appears that mefloquine is mainly excreted into bile and faeces. The elimination half-life of mefloquine is three weeks. After a single dose in healthy adults it was between 12-37 days on average.

INDICATIONS:
MEFLIAM tablets are indicated for prophylaxis of Plasmodium falciparum malaria, in regions where P. falciparum strains resistant to 4-aminoquinolines (e.g. chloroquine) occur. MEFLIAM may be effective against malaria parasites resistant to proguanil, pyrimethamine-sulfonamide combinations.

CONTRA-INDICATIONS:
MEFLIAM is contra-indicated in the following:
Patients with known hypersensitivity to mefloquine or related compounds (e.g. quinine and quinidine).
Patients with depression or a past history of depression, generalized anxiety disorder, psychosis, including schizophrenia or other psychiatric disturbances.
Patients with a history of convulsions.
Children of body weight less than 5 kg.
Patients with impaired renal or hepatic function.
The safety in pregnancy and lactation has not been established.

WARNINGS:
Mefloquine may cause psychiatric symptoms in some patients, ranging from anxiety, paranoia and depression to more serious hallucinations and psychotic behaviour. In some instances, these symptoms have continued long after mefloquine was stopped, according to reports. Rare cases of suicide and suicidal ideation have been reported, although no causal relationship with mefloquine has been confirmed. To minimize the chances of these adverse events, mefloquine should be avoided in patients with depression or a past history of depression, generalized anxiety disorder, psychosis, including schizophrenia or other psychiatric disturbances.
If psychiatric symptoms such as unexplained anxiety, depression, restlessness or confusion are evident during mefloquine prophylaxis, the medicine must be discontinued and alternative prophylaxis instituted, as these could be prodromal to a more serious neuropsychiatric event.
Quinine and quinidine which are commonly required for the treatment of severe malaria, are contra-indicated when MEFLIAM prophylaxis has been used.

Concomitant administration of mefloquine and other related compounds (quinine, quinidine and chloroquine) may produce ECG abnormalities and increase the risk of convulsions.
As teratogenicity has been shown in animal studies, reliable contraception is recommended whilst taking MEFLIAM tablets and for three months after the last dose. Data in human exposure during the first trimester are insufficient to conclude safety in pregnancy.
Mefloquine is excreted into breast milk and therefore if it must be taken, breast feeding should be discontinued.
Mefloquine has been administered for longer than 1 year. If administered for a prolonged period (longer than 3 months), periodic monitoring, including liver function tests, should be performed. Although the retinal abnormalities seen with long-term chloroquine use in humans, have not been found with mefloquine, dose-related ocular lesions have been observed in rats after long-term use of mefloquine at 12.5 mg/kg/day (3-4 x human prophylactic dosage) or higher. Periodic ophthalmic examinations are therefore also recommended.
Caution is advised in patients who have cardiac conduction diseases because asymptomatic sinus bradycardia and other conduction abnormalities have been reported.
Caution must be exercised during driving, piloting aircraft, scuba diving, and operating machines as dizziness, disturbed sense of balance or neuropsychiatric reactions have been reported whilst taking MEFLIAM and for three weeks afterwards.
Mefloquine and halofantrine used simultaneously may lead to a potentially fatal prolongation of the QTC interval.
MEFLIAM may cause toxic encephalopathy of unknown etiology during prophylaxis.
There is no evidence that dose adjustment is required for patients with renal impairment. However, since the clinical evidence is limited, MEFLIAM should be used with caution in these patients.
Mefloquine prophylaxis should not exceed three months as long term prophylaxis is thought to contribute to the development of resistant strains of P. falciparum.
Resistance to mefloquine has been documented in some areas.
If flu-like symptoms develop in patients who have been in a malaria area they should inform their doctors accordingly.
Additional preventative measures: As preventative medication with all antimalarials is not 100% effective, the following measures to prevent mosquitoes from biting should be taken to reduce the risk of contracting malaria:
I. visiting endemic areas during the dry season or in years when rainfall is low;
II. high risk persons should avoid malaria areas altogether, (high risk persons include babies and young children less than 5 years of age, pregnancy, immunocompromised individuals such as those on long term steroids, cancer patients, chemotherapy. AIDS patients and those who have had their spleen removed.);
III. not going outside between dusk and dawn, when mosquitoes are most active;
IV. applying insect repellant to exposed skin and clothes;
V. wearing long sleeves and long trousers at night;
VI. using mosquito nets, screens, coils and pads.

DOSAGE AND DIRECTIONS FOR USE:
The following weekly doses of MEFLIAM are recommended:
  Body weight:        Weekly dose for prophylaxis:
  Up to 19 kg        1/4 tablet (62,5 mg)
  20-30 kg        ½ tablet (125 mg)
  31-45 kg        3/4 tablet (187,5 mg)
  >45 kg        1 tablet (250 mg)
Experience with MEFLIAM in infants less than 3 months old or weighing less than 5 kg does not exist.
The first dose should betaken one week before arrival in an endemic area and subsequent weekly doses should be taken on the same day of each week. Prophylaxis should be continued for four weeks after leaving the malarial area, and should not exceed 3 months' duration. The tablets should be taken after food with plenty of fluids.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Dizziness or disturbed sense of balance, nausea, vomiting, loose stools or diarrhoea, abdominal pain and loss of appetite. Less frequent reactions reported include headache, somnolence and sleep disorders (insomnia, abnormal dreams), myalgia, feeling of weakness, visual disturbances, palpitations, bradycardia, irregular pulse and extrasystoles, AV-block, hair loss, rash or pruritus, urticaria, convulsions, psychological changes, transient elevation of transaminases, leucopoenia or leucocytosis and decrease of platelets. Erythema multiforme and Stevens-Johnson syndrome have been reported. Transient cardiac conduction alterations and paraesthesia have been observed in patients taking mefloquine. These adverse events can be observed several weeks after the last dose has been taken.
Psychiatric reactions, sometimes disabling and prolonged, have been reported in association with mefloquine. These include aggression, agitation, anxiety, confusion, convulsions, depression, emotional instability, encephalopathy, forgetfulness, hallucinations, sensory and motor neuropathies (including ataxia, paraesthesia and tremor), panic attacks, paranoia, psychosis and restlessness. Rare cases of suicidal ideation and suicide have been reported, although no causal relationship with mefloquine has been established.
Special precautions:
Caution is advised in renal compromised patients, in compromised hepatic function and in elderly patients as there may be different pharmacokinetic parameters for these groups.
If signs of unexplained anxiety, depression, restlessness or confusion are evident, the medication must be stopped as these could be prodromal symptoms of a more serious neuropsychiatric event.
Interactions:
Concurrent use of beta-blockers, calcium channel blocking agents, quinidine or quinine with MEFLIAM tablets may result in sinus bradycardia, prolonged QT intervals or cardiac arrest; the risk of seizures may also be increased with quinine; concurrent use should be avoided; if concurrent use is necessary, close monitoring of patient response is recommended; in addition, patients should be advised to take mefloquine at least 12 hours after the last dose of quinidine or quinine.
Mefloquine and halofantrine used simultaneously may lead to a potentially fatal prolongation of the QTC interval.
Mefloquine may lower serum concentrations of anticonvulsants (e.g. valproic acid, carbamazepine, phenobarbital or phenytoin) and cause loss of seizure control; monitoring of these anticonvulsant serum concentrations is recommended and dosage adjustments may be necessary during and after therapy with mefloquine.
The concurrent use of the oral typhoid vaccine with mefloquine may decrease the effectiveness of the oral typhoid vaccine; doses of the two medications should be separated by 7 to 10 days. It must be remembered that the first dose of MEFLIAM should be taken one week before entering the malaria area.
Patients who are taking anticoagulants and oral antidiabetic agents should be monitored and have the relevant parameters checked before taking these with mefloquine as it is not known if there are any interactions.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In the event of an overdose with mefloquine, the symptoms would be those specified under "Side-effects and special precautions" but more pronounced. There is no known specific antidote for an overdosage, treatment should include standard gastric decontamination procedures and routine symptomatic and supportive treatments. Cardiac function, neurological and psychiatric status should be monitored for at least 24 hours.

IDENTIFICATION:
Flat, white, circular uncoated tablets with bevelled edges. One side has a cross breakline and the other side is plain.

PRESENTATION:
MEFLIAM Tablets are available in blister packs of 6 and 8 tablets.

STORAGE INSTRUCTIONS;
Store below 25°C. Keep out of reach of children.
Protect from moisture.

REGISTRATION NUMBER:
31/20.2.6/0502

NAME AND BUSINESS ADDRESS OF APPLICANT:
Cipla Medpro (Pty) Limited
Rosen Heights, Pasita Street, Rosen Park, Bellville, 7530

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
November 2002

© Cipla Medpro 2002

Cipla Medpro logo

2793 H

IY1

Updated on this site: December 2004
Source: Community Pharmacy

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004