Artelumex Forte Artemether and Lumefantrine Tablets

ARTELUMEX™-FortE Tablets
ARTEMETHER 80 mg + LUMEFANTRINE 480 mg

 

COMPOSITION

Each film coated tablet contains:

Artemether 80mg

Lumefantrine 480 mg

Excipients q.s.

Colourants: Lake of Tartrazine & Titanium Dioxide USP

 

DESCRIPTIONS

Antimalarials, Artemisinin based Combination Therapy (ACT).

 

PROPERTIES

Artemether is the most active derivate of the artemisinines, a new class of antimalarial drugs derived from artemisinin. The later compound is extracted from the plant Artemisia annua and Artemether is prepared semi-synthetically. Lumefantrine is a synthetic aryl amino alcohol similar to Mefloquine and Halofantrine.

 

INDICATIONS

Treatment of malaria caused by all forms of Plasmodium including severe malaria caused by multiple drug resistant strains of P falciparum.

 

PHARMACODYNAMICS

Both Artemether and Lumefantrine have their own action site in the malarial parasite.

The presence of the endoperioxide bridge in Artemether (generating singlet oxygen and free radicals: those are very cytotoxic to the plasmodia) appears to be essential for antimalarial activity. Morphological changes of the parasitic membranes induced by Artemether have been described, being the result of free-radical action. Lumefantrine interferes more in the polymerization processes.

Other in vitro tests 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 essentially as a blood schizonticide, ARTELUMEX-Forte did clear gametocytes in comparative clinical trials.

 

PHARMACOKINETICS

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 antimalarial itself, has a T½ of about 2-4 hours. The degree of binding to plasma proteins varied markedly according to the species studied. The binding of Artemether with plasma protein 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% in fasted 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. Lumefantrine, is N-debutylated in human liver microsomes. This metabolites 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 treated patients will be 4 to 6 days. Lumefantrine and its metabolites are found in bile and faeces.

 

PRECAUTIONS AND CONTRA-INDICATIONS

Hypersensitivity to Artemether and Lumefantrine. There are no strict contraindications for the use of Artemether in children. Nevertheless, 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 known to prolong the QT interval, such as certain antibiotics (macrolides, fluoroquinolones, imidazole) or who are predisposed to cardiac arrhythmias.

It is advisable not to use drugs during pregnancy but in view of the high risk of malaria during pregnancy for mother and foetus, the responsible physician may consider it essential as in the case of cerebral malaria to treat a pregnant woman. Artemisinin derivative, Artemether are the fastest acting schizontocides and rapid clearance of parasites is essential. Since ARTELUMEX-Forte has been designed for its use in children, it is unlikely that this problem arises.

ARTELUMEX-Forte should not be taken during breastfeeding. Due to the long elimination half-life of Lumefantrine, it is recommended that breastfeeding should not start until at least one week after stopping an Artemether/Lumefantrine combinatIon treatment.

 

PREGNANCY AND LACTATION

ARTELUMEX – Forte must not be used in the first trimester of pregnancy in situations where other suitable and effective antimalerials are available.

Pregnancy

There is insufficient data from the use of Artemether and Lumefantrine in pregnant woman. Based on animal data, ARTELUMEX – Forte is suspected to cause serious birth defects when administered during the first trimester of pregnancy. Reproductive studies with Artemether have shown evidence of post-implantation losses and teratogenicity in rats and rabbits. Other artemisinin derivatives have also demonstrated teratogenic potential with an increased risk during early gestation ARTELUMEX-Forte treatment must not be used during the first trimester of pregnancy in situations where other suitable and effective antimalarials are available. However it should not be withheld in life threatening situations, where no other effective antimalarials are available, during the second and third trimester, treatment should only be considered if the expected benefit to the mother outweighs the risk to the foetus.

Lactation

Animal data suggest excretion into breast milk but no data are available in humans. Women taking ARTELUMEX-Forte should not breastfeed during their treatment. Due to the long elimination half-life of Lumefantrine (4 to 6 days), it is recommended that breast-feeding should not resume until at least one week after the last dose of ARTELUMEX-Forte unless potential benefits to the mother and child outweigh the risks of ARTELUMEX-Forte treatment.

Effect on ability to drive and use machine: None.

 

DRUG INTERACTIONS

Artemether potentiates the antimalarial activity of other antimalarials.

As grapefruit juice retards the metabolism of some antimalarials, it would be better not to drink grapefruit juice while taking ARTELUMEX-Forte.

 

SIDE EFFECTS

With Artemether virtually no side effects 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 casual relationship is unclear.

Some antimalarials such as Halofantrine and Quinine can influence the ECG pattern. Attention should be made to patient previously treated with those antimalarials. A reasonable period should be taken into account before starting treatment with Lumafantrine combinations. For such patients, mono therapy with Artemisinin derivatives is recommended.

Sometimes rash, trouble sleeping, nausea, vomiting, diarrhea, coughing may occur. They need medical attention when persisting.

 

DOSAGE AND ADMINISTRATION

Weight in Kg Total Tablets Dosage Regimen
Day 1 Day 2 Day 3
0 Hour 8 Hours 24 Hours 36 Hours 48 Hours 60 Hours
35 and above 6 1 1 1 1 1 1

Second dose to be taken after 8 hours of the first dose.

Better taken with food especially fatty meal. Tablets for oral administration.

 

DO NOT EXCEED THE DOSE PRESCRIBED

Hepatobiliary disorders
Liver function tests increased Uncommon Common
Psychiatric disorders
Sleep disorders Very common Common
Insomnia Common Uncommon

* These adverse reactions were reported during post-marketing experience. Because these spontaneously reported events are from a population of uncertain size, it is difficult to estimate their frequency.

 

OVERDOSE

Experience of overdosage with Artemether and Lumefantrine is limited. In case of suspected overdosage symptomatic and supportive therapy should be given as appropriate, which should include monitoring of ECG and serum electrolytes.

 

STORAGE

Store below 30°C, at a dry place. Protect from light Keep medicines out of reach of children.

 

PRESENTATION

Each carton contains blister of 6 Tablets.

NAFDAC Reg. No.: B4-6185

 

Manufactured by

Medibios Laboratories Pvt. Ltd.

Plot No. J-76, MIDC, Tarapur, Taluka – Palghar Dist.

Thane 401 506, Maharashtra, INDIA.

 

Exported by

MEYER ORGANICS PVT. LTD.

A-177, Wagle Estate, Thane-400 604 (Mumbai) INDIA.

 

In technical collaboration with

Omega-Meyer Ltd. Jersey

 

Marketed by

Adler Products Ltd

32, Oduyemi Street, Ikeja,

Lagos, Nigeria.

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