Gvither Artemether and Lumefantrine Tablets

Gvither™ Tablets

(Artemether + Lumefantrine Tablets)

 

COMPOSITION

Gvither 20/120 Tablets

Each film coated tablet contains

Artemether 20mg

Lumefantrine 120mg

Excipients q.s.

Colour: Tartrazine & Titanium Dioxide

 

Gvither PIus 40/240 Tablets

Each film coated tablet contains:

Artemether 40 mg

Lumefantrine 240 mg

Excipients q.s.

Colour : Tartrazine & Titanium Dioxide

 

Gvither PIus 80/480 Tablets

Each film coated tablet contains:

Artemether 80 mg

Lumefantrine 480 mg

Excipients q.s.

Colour : Tartrazine & Titanium Dioxide

 

PROPERTIES

Artemether is the most active derivate of the Artemisinines, a new class of antimalarial drugs derived from Artemisinin. The latter compound is extracted from the plant Artemisia Annua and Artemether is prepared semi-synthetically.

Lumefantnne is a synthetic aryl amino alcohol similar to mefloquine and halofantrine.

 

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Both components of Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets/ Gvither Plus 80/480 Tablets 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 test suggests 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, Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets / Gvither Plus 80/480 Tablets 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 T1/2 of 2-4 hours. Dihydroartemisinin, being a potent antimalarial itself, has a T1/2 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% 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.

Lumefantrine is N-debutylated in human liver microsomes. 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.

 

PRECAUTIONS AND CONTRAINDICATIONS

Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets / Gvither Plus 80/480 Tablets is contraindicated in individuals hypersensitive to Artemether and Lumefantrine. Therefore, there are no strict contra-indications 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 derivatives like Artemether are the fastest acting schizontocides and rapid clearance of parasites is essential. Since Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets / Gvither Plus 80/480 Tablets has been designed for its use in children it is unlikely that this problem arises. Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets / Gvither Plus 80/480 Tablets 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 at least one week after stopping an Artemether/ Lumefantrine combination treatment.

 

INDICATIONS

Treatment of malaria including multidrug resistant strains of P. falciparum.

 

DOSAGE AND ADMINISTRATION

Gvither 20/120 Tablets

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
5-14 6 1 1 1 1 1 1
15-24 12 2 2 2 2 2 2
25-34 18 3 3 3 3 3 3
35-and more (Adults) 24 4 4 4 4 4 4

Gvither 40/240 Tablets

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
15-24 6 1 1 1 1 1 1
25-34 9
35-and more (Adults) 12 2 2 2 2 2 2

Gvither Plus 80/480 Tablets

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
35kg and above 6 1 1 1 1 1 1

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

Better taken with food especially fatty meal.

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

 

DRUG INTERACTIONS

Specific negative drug drug interactions were not seen. Artemether potentialises 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 Gvither 20/120 Tablets / Gvither Plus 40/240 Tablets / Gvither Plus 80/480 Tablets.

 

SIDE EFFECTS

With Artemether virtually no side effect have been seen. Laboratory abnormalities such so slight rise in transaminanes 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 those antimalarials. A reasonable period should be taken in account before to start a treatment with lumefantrine combinations. For those patients physicians 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 also 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 of 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.

 

PRESENTATION

Gvither 20/120 Tablets Each carton contains blisters of 3 x 8 Tablets.

Gvither Plus 40/240 Tablets Each carton contains blisters of 2 x 6 Tablets.

Gvither Plus 80/480 Tablets – Each carton contains blisters of 1 x 6 Tablets.

 

DATE OF PUBLICATION /REVIEW

29/04/2015

 

SHELF LIFE

2 Years from the Date of Manufacturing.

 

NAFDAC REG. No: A4-6730

 

Marketed by

SAGREEN PHARMACEUTICALS LTD.

3, Okunfolami Street, Anthony Village, Lagos.

 

Manufactured by

BLISS GVS PHARMA LTD.

 

Factory: 10, Dewan Udyog Nagar,

Aliyali, Paighar, Maharaohtra -401 404, INDIA.

 

Registered Office: 102, Hyde Park,

Saki Vihar Road, Andheri (E), Mumbai -400 072, INDIA.

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