BG MAL 560 tablet

PROPERTIES:

Artemether is the most active derivate of the Artemesinines a new class of antimalaria drugs derived from Artemisinin. The latter compound is extracted from the plant Artemisia Annua and Artemether is prepared semi-synthetically. Lumenfantrine is a synthetic aryl amino alcohol similar to mefloquine and hal-fantrine.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics:

Both components of BG MAL–560 have their own action sites in the malaria parasite. The presence of the perioxide bridge in Artemether (generating single oxygen and free radicals: those are very cytotoxic to the plasmodia) appears to be essential for antimalaria activity. Morphological changes of the parasitic membranes induced by Artemether have been described, being the result of free-radical action.

Lumefantrine interferes more in plymerization processes. Other in vitro test suggest that both cause a marked diminution of nucleic acid synthesis. Inhibition of protein synthesis as the basic mechanism of action is suggested in studies which showed morphological changes in ribosomes as well as in the endoplasmic reticulum. Although Artemether acts essential as a blood schizonticide, BG MAL-560 did clear gametocytes in pmparative clinical trials. Orally administered Artemether is rapidly absorbed reaching therapeutic levels within 60-90 minutes.

Artemether is metabolized in the liver to the demethylated derivate dihydroartemisinin (DHA). The elimination is rapid, with a T½ of 2-4 hours. Dihydroartemisinin, being a potent antimalaria itself, has a T½ of about 2-4 hours. The degree of binding to plasma proteins in man is about 50%. Radioactivity distribution of Artemether was found to be equal between cells and plasma.

The absorption of Lumefantrine is highly influenced by lipids and food intake (from 10% by fasten to 100% at normal diet). Therefore parents should be encouraged to give the medication with some fatty food as soon as it can be tolerated. Lumenfantrine is N-debutylated in human livermicrosomes. This metabolite has 5 to 8 fold higher antiparasitic effects than lumefantrine. Lumefantrine is found to be highly protein bound (95%). The elimination half life in malaria attaint patients will be 4 to 6 days. Lumefantrine and his metabolities are found in bile and faeces.

Treatement of malaria including resistant strains of P.falciparum.

BG MAL-560 is contraindicated in individuals hypersensitive to Artemether and Lumefantrine. Therefore, there are no strict contra-indications for the use of Artemether in children. Neverthless, no correlation has been found between QTc interval prolongation and plasma concentrations of lumefantrine caution is advised to patients who are taking drugs that are know tp prolong the QT interval, such as certain antibiotics (macrolides, fluoroquinolones, imidazole) or who are predisposed to cardiac arrhythmias.

It is advisable not to use dugs during pregnancy but in view of the high risk of malaria during pregnancy for the mother and foetus, the responsible physcian may consider it essential, as in the case of cerebral malaria, to treat a pregnant woman. Artemiscinin derivatives like Artemether are the fastest acting schizontocides and rapid clearance of parasites is essential.

Since BG MAL-560 has been designed for its use in children it is unlike that this problem arises. BG MAL-560 should not be taken during breast-feeding. Due to the long elimination half-life of lumefantrine, it is recommended that breast-feeding should not start until atleast one week after stopping an Artemether/Lumenfantrine combination treatment.

BG MAL-560 is contraindicated in individuals hypersensitive to Artemether and Lumefantrine.

Therefore, there are no strict contra-indications for the use of Artemether in children. Neverthless, no correlation has been found between QTc interval prolongation and plasma concentrations of lumefantrine caution is advised to patients who are taking drugs that are know tp prolong the QT interval, such as certain antibiotics (macrolides, fluoroquinolones, imidazole) or who are predisposed to cardiac arrhythmias.

It is advisable not to use dugs during pregnancy but in view of the high risk of malaria during pregnancy for the mother and foetus, the responsible physcian may consider it essential, as in the case of cerebral malaria, to treat a pregnant woman.

Artemiscinin derivatives like Artemether are the fastest acting schizontocides and rapid clearance of parasites is essential. Since BG MAL-560 has been designed for its use in children it is unlike that this problem arises.

BG MAL-560 should not be taken during breast-feeding.

Due to the long elimination half-life of lumefantrine, it is recommended that breast-feeding should not start until atleast one week after stopping an Artemether/Lumenfantrine combination treatment.

Specific negative drug

• drug interactions were not seen.

Artemether potentialises the antimalarial activity of other antimalarias.

As grapefruit juice retards the metabolism of some antimalarias, it would be better not to drink grapefruit juice while taking BG MAL-560.

With Artemether virtually no side effect have been seen. Laboratory abnormalities such as slight rise in transaminases and a decrease in reticulocyte count are rare and transient. A lowering of sinus frequency without causing ECG changes has been noticed. At high doses transient abdominal pain, tinnitus and diarrhea have been described but a causal relationship is unclear.

Some antimalarials as halofantrine and quinine can influence the ECG pattern. Attention should be made to patients previously treated with lumenfantrine combinations. For those patients physcians will be prescribed Artemisinin derivatives in mono therapy in cause of severe paludism. Sometimes it could be possible that the following common side effect occur; rash, check this with your doctor.

Other common side effects may occur as trouble of sleeping, nausea, vomiting, diarrhea, coughing. They need medical attention when persisting.

RESISTANCE AND RECRUDESCENCE:

Resistance of plasmodia to Artemether has not been observed. It is aslo unlikely to occur in view of the specific mechanism of action which is very cytotoxic for plasmodia (opening of a peroxide bridge). An apparent resistance is sometimes seen but is mainly due to multiple broods as plasmodia developing at different times in the same patient. In controlled studies recrudescence does not exceed 10%. In case of recrudescence (renal or apparent) a new complete treatment for three days is advisable.

BG MAL 560 TABLETS

Second dose to be taken 1after 8 hours of first dose or As directed by the physcian.

Better taken with food especially fatty meal.

Breastfeeding: Data on excretion in breast milk are not available for humans.

SHELF LIFE: 2 years from the date of manufacturing.

Store in a cool (between 8°C & 25°C), dry & dark place.

Keep medicines out of reach of children