LYNSUNATE® FORTE 80/480 TABLETS
Artemether 80mg and Lumefantrine 480mg
COMPOSITION AND PACKAGING
Each tablet of Lynsunate forte® 80/480 tablet contains Artemether 80mg and Lumefantrine 480mg.
Each blister contains 6 tablets.
ACTIONS AND PHARMACOLOGY
LYNSUNATE® comprises a fixed ratio of 1:6 parts of Artemether and Lumefantrine, respectively. The site of anti-parasitic action of both components is the food vacuole of the malaria parasite, where they are thought to interfere with the conversion of haem, a toxic intermediate produced during haemoglobin breakdown, to the non-toxic haemozoin, malaria pigment. Lumefantrine is thought to interfere with the polymerization process, while Artemether generates reactive metabolites as a result of the interaction between its peroxide bridge and haem iron.
Both Artemether and Lumefantrine have a secondary action involving inhibition of nucleic acid and protein synthesis within the malaria parasite. Data from in-vitro and in-vivo studies show that LYNSUNATE® did not induce resistance.
LYNSUNATE® is active against blood stages of plasmodium vivax, but is not active against hypnozoites. Therefore, sequential treatment with primaquine should be used to achieve hypnozoite eradication (see CONTRAINDICATIONS).
LYNSUNATE® is indicated for:
• Treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum
• Treatment of mixed infections including Plasmodium falciparum
• Treatment of malaria infections resistant to other drugs
DOSAGE AND ADMINISTRATION
The route of administration is oral. A six-dose regimen is recommended during a three day period.
|Body weight in kg||Above 35kg|
|Age in years||>14|
|After 8 hours||1|
|Day 2 Morning||1|
|Day 2 Evening||1|
|Day 3 Morning||1|
|Day 3 Evening||1|
Pharmacokinetic characterisation of LYNSUNATE® is limited by the lack of an intravenous formulation, and very high inter- and intra- subject variability of Artemether and Lumefantrine plasma concentrations and derived pharmacokinetic parameters (AUC, C max).
Artemether is absorbed fairly rapidly with peak plasma concentrations reached about 2 hours after dosing. Absorption of Lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with peak plasma concentration about 6-8 hours after dosing. Food enhances the absorption of both Artemether and Lumefantrine. Patients should therefore be encouraged to take the medication with a normal diet as soon as food can be tolerated.
Artemether and Lumefantrine are both highly bound to human serum proteins in vitro (97.9% and 99.9%, respectively)
Artemether is rapidly and extensively metabolised (substantial first-pass metabolism) both in vitro and in humans. Human liver microsomes metabolise Artemether to the biologically active main metabolite Dihydroartemisinin (demethylation), predominantly through the enzyme CYP3A/5. In-vivo data indicate that artemisinins have some capacity to induce cytochrome isoenzymes CYP2C19 and CYP3A4. Lumefantrine is N-debutylated, mainly by CYP3A4 in human liver microsomes. In vitro Lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations.
Artemether and Dihyroartemisinin are rapidly cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated very slowly with a terminal half-life of 2-3 days in healthy volunteers and 4 6 days in patients with falciparum malaria. Demographic characteristics such as sex and weight appear to have no clinical relevant effects on the pharmacokinetics of LYNSUNATE®.
LYNSUNATE® is usually well tolerated. The most common side effects of products containing Artemether and Lumefantrine include nausea, vomiting, dizziness, fatigue, asthenia, rash, and pruritus.
LYNSUNATE® is contraindicated in those persons with known hypersensitivity to the active substances or to any of the excipients. It is also contraindicated in patients with a history of cardiac arrhythmias, bradycardia, hypokalaemia, hypomagnesaemia; patients already taking neuroleptics, anti-depressive agents, macrolides, fluoroquinolones, imidazoles, terfenadine, astemizole, and cisapride.
LYNSUNATE® is usually well tolerated. The most common adverse reactions of products containing Artemether and Lumefantrine are palpitations, anorexia, nausea, abdominal pain, athralgia, myalgia, headache, dizziness, sleep disorder, somnolence, paraesthesia, hypoaesthesia, cough, abnormal gait, ataxia, involuntary muscle contractions and diarrhea.
Store the product in a dry place, away from direct sunlight, and below 30 degrees centigrade.
Keep all medicines out of reach of children.
NAFDAC Reg. No.: A4-5641
LYN-EDGE PHARMACEUTICALS LTD,
113, Old Aba Road, Port Harcourt,
Rivers State, Nigeria.
SHANDONG YIKANG PHARMACEUTICAL CO., LTD.
No.3288 Yikang Avenue,Tengzhou City, Shandong Province ,China.