FANSIMEF^®

Sulfadoxine + pyrimethamine + mefloquine

Composition · Properties, effects · Absorption · Elimination · Indications · Dosage · Restrictions on use · Undesirable Effects · Interactions · Over dosage · Countermeasures · Packs

1 tablet contains 500mg sulfadoxine, 250mg mefloquine (as hydrochloride) and 25 mg pyrimethamine.

The components of FANSIMEF^® are complementary. For instance, between sulfadoxine and pyrimethamine,the active ingredients of the well known antimalarial FANSIMEF^® there is pronounced mutual potentiation (synergism), while mefloquine, a highly potent erythrocytic schizonticide, has an additive effect when combined with sulfadoxine-pyrimethamine. Compared with the individual ingredients, the combination of active substances contained in FANSIMEF^® considerably delays emergence of resistance in rodent malaria models. The resistance-delaying property of FANSIMEF® is of great importance in view of the ability of the antimalaria pathogens in man, in particular Plasmodium Falciparum, to develop resistance to antimalarial drugs relatively quickly.

The central action of FANSIMEF^® in malaria therapy consists in killing the asexual erythrocytic forms of the malaria pathogen. FANSIMEF^® is also effective against malaria parasites which have developed resistance to other antimalarials such as chloroquine and other 4 –aminoquinoline derivatives, proguanil, pyrimethamine and sulfonamide-pyrimethamine combinations.

After ingestion of 1 tablet of FANSIMEF^®, peak plasma levels for mefloquine (0.36 ug/ml) were reached after about 16 hours and for sulfadoxine (58.4 ug/ml) and pyrimethamine (0.18 ug/ml) after two to four hours (mean values obtained from 12 volunteers). Binding to plasma protein was 97.6% for mefloquine 87.6% for sulfadoxine and 92.5% for pyrimethamine.

A long elimination half-life is characteristic of all three components.The average values are approximately 400 hours for mefloquine, approximately 200 hours for sulfadoxine and approximately 100 hours for pyrimethamine. Both sulfadoxine and pyrimethamine are excreted mainly via the kidneys. On the basis of animal experiments in rats, it can be assumed that mefloquine is largely excreted in the form of metabolites in the bile and feaces.

FANSIMEF^® is indicated particularly for the therapy of P.faciparum malaria resistant to other antimalarial agents. When treating P.vivax and P. malariae with FANSIMEF^®, subsequent prophylaxis of recurrence with an 8-amino quinoline derivative (e.g. primaquine) should be considered for elimination of the parasites in the liver cells.

Nonimmune patients: a single dose of 3 tablets.

Semiimmune patients: for patients weighing 60kg or less, a single dose of 2 tablets; for patients weighing more than 60kg, a single dose of 3 tablets.

The tablets should be swallowed whole with a good deal of fluid, but not, if possible, on an empty stomach.

Mefloquine and pyrimethamine can be teratogenic in laboratory animals (rats, mice). For this reason FANSIMEF^® may not be given in early pregnancy unless its use is absolutely imperative. FANSIMEF^® should not be given to neonates in the first weeks of life. FANSIMEF^® is contraindicated in patients with known hypersensitivity to sulfanamides. In particular, treatment with FANSIMEF^® must not be repeated if symptoms of hypesensitivity to sulfanomides have occurred.

For the sake of completeness, the side effects of mefloquine and of sulfadoxine plus pyrimethamine (FANSIMEF^®) are listed in decreasing order of frequency, although not all have been observed in connection with FANSIMEF^®
Undesirable effects of mefloquine: dizziness, nausea, vomitting, soft stools and diarrhea, gastric discomfort, loss of appetite, headache, bradycardia, skin rash and pruritus, asthenia.
Very rarely: temporarily raised transaminases, transient mental changes (depressive mood or confusion).
Undersirable effects of sulfadoxine plus pyrimethamine: gastrointestinal disturbances (nausea and feeling of fullness), skin reactions (rashes and pruritus); rarely in the event of individual hypersensitivity: severe skin reactions (Stevens-Johnson and Lyell’s syndromes); extremely rarely: blood dyscrasias (leukopenia, megalobastic anemia and thrombocytopenia) and liver cell damage.

FANSIMEF^® should not be administered concurrently with quinine. Severe cases however can be treated intravenously for one or more days initially with quinine and subsequently with FANSIMEF^® Potentiation of the side effects of quinine and mefloquine can be largely avoided if FANSIMEF^® is administered not less than twelve hours after the last dose of quinine.

Overdosage of FANSIMEF^® may produce symptoms such as dizziness, nausea, vomiting, atrioventricular conduction disorders, mental excitation and possibly convulsions. Hematopoietic changes such as megaloblastic anemia, leukopenia or thrombocytopenia may also occur.

Gastric lavage, fluid replacement, careful cardiac monitoring (ECG), and for convulsions diazepam or a barbiturate patenterally. Periodic blood counts should be performed up to four weeks after the overdosage. In the event of the above mentioned hematopoietic changes, folinic acid (leucovorin) should be administered intramuscularly.