ARCEV A Tablets / Dry Suspension stage of P.

vivax but not active against hypnozoites

(Lumefantrine
Artemether+
) Artemether / Lumefantrine must be used for the malaria infections acquired in areas where
the parasites may be resistant to other anti-malarial drugs
DESCRIPTION:
Arceva is a new treatement of malaria. It is the fixed combination of Artemether (Methyl-ether “World Health Organization recommends Artemether / Lumefantrine as a first line
derivative of Artemisinin) & Lumefantrine (fluorene derivative belonging to aminoalcohol class) treatement for the acute uncomplicated P.falciparum malaria for both multi-drug resistant
COMPOSITION: areas & drug sensitive areas”
Arceva 20/120mg Tablets: Arceva 40/240mg Tablets:
Each tablet contains: Each tablet contains: DOSAGE & ADMINISTRATION:
Artemether MS..............20mg Artemether MS..............40mg Patients with acute malaria are frequently averse to food. The dose may be encouraged to
Lumefantrine MS.........120mg Lumefantrine MS.........240mg resume normal eating as soon as food can be tolerated since this improves absorption of
Artemether and Lumefantrine. In the event of vomiting within 1 hour of administration a repeat
Arceva 80/480mg Tablets: Arceva 15/90mg/5ml Suspension: dose should be taken
Each tablet contains: Each 5 ml contains: 6-dose regimen should be given 3 days at oral treatment 1st dose as the time of initial diagnosis
Artemether MS..............80mg Artemether MS..............15mg & than at 8, 24, 36, 48 & 60 hrs.
Lumefantrine MS.........480mg Lumefantrine MS............90mg
Dosage according to body weight:
CHEMICAL STRUCTURE: HOCHCH2NBu2
ARCEVA 20mg/120mg Tablets:
CH3
H
5kg to 14kg: 1 B.I.D for 3 days
0

0
CH3
0
CI CI ARCEVA 40mg/240mg Tablets:
H 0 Adults & over 35kg: 2 B.I.D for 3 days
0CH 3
CH3 CH Cl
25kg to 34kg: 1 1/2 B.I.D for 3 days
15kg to 24kg: 1 B.I.D for 3 days
Artemether Lumefantrine
PHARMACODYNAMICS: ARCEVA 80mg/480mg Tablets:
Arceva comprises a fixed combination of 1 part of Artemether and 6 parts of Lumefantrine Adults & over 35kg: 1 B.I.D for 3 days
Artemether has quick onset of action while Lumefantrine has longer duration of action. Both
exerts their anti-parasitic action at the blood stage of malarial parasite, where they convert the ARCEVA 15/90mg/5ml Suspension:
haem (a toxic metabolite produced during haemoglobin breakdown) to nontoxic haemozoin Once Daily for Three Days
(malaria pigment). Lumefantrine interfaces with the polymerization process, while Artemether
generates reactive metabolites as a result of interaction between its peroxide bridge & haem Body Weight (Kg) 5 - 7.4 7.5 - 9.9 10 - 12.4 12.5 - 14.9 15 - 17.4 17.5 - 19.9
iron. Both components also have a secondary action involving inhibition of nucleic acid and
Dosage 7 ml 10 ml 14 ml 17 ml 20 ml 24 ml
protein synthesis within the malarial parasite
There is a synergism of independant actions of both Artemether and Lumefantrine, which has Or as directed by the physician
been shown to potentiate the blood schizontocidal effects. It is also effective against drug resistant
strains of P.falciparum malaria. Comprehensive in vitro studies using laboratory maintained and UNWANTED SIDE EFFECTS:
fresh field parasite isolates from different malaria endemic areas have shown marked synergic Artemether / Lumefantrine is well tolerated and there is no drug induced serious unwanted
effect of these two components side effects. The most common adverse experiences (> 1%) in patients treated with Artemether
/ Lumefantrine combination are abdominal pain, diarrhoea, vomiting, nausea, palpitation,
Results of comparative clinical trials indicate that this Artemether and Lumefantrine combination headeache, dizziness, arthralgia, cough, myalgia, pruritis, rash, asthenia and fatigue
also clears gametocytes more rapidly than other conventional antimalarials
The preclinical investigations and the clinical trial programms revealed no cardiotoxicity with
PHARMACOKINETICS: Artemether / Lumefantrine combination, and to date there have been no reports of adverse
Absorption: clinical cardiac events. Recent studies comparing Artemether / Lumefantrine with Halofantrine
Artemether is absorbed quickly with peak plasma concentrations reaching in about 2 hours after in human showed a clear distinction between the two substances and confirmed no sign of
dosing, while absorption of Lumefantrine is started after a lag-time of up to 2 hours, with peak cardiotoxicity with Artemether / Lumefantrine combination
plasma concentration in about 6-8 hours after dosing. Food enhances the absorption of Artemether
& Lumefantrine. In healthy volunteers the relative bioavailability of Lumefantrine increases sixteen CONTRA-INDICATION:
fold compared with intake on empty stomach. High fat content is conducive for absorption. Food Artemether / Lumefantrine is contra-indicated to those patients which have a history of
has also been shown to increase the absorption of Lumefantrine in patients with malaria. Usually hypersensitivity to Artemether / Lumefantrine
in acutely ill patients there is a tendency of consuming low fat diet. Absorption of Lumefantrine
under fasted conditions is very poor. Patients should therefore be encouraged to take the PRECAUTION:
medication with a normal diet as soon as food can be tolerated Pregnancy:
There are no adequate data from the use of Artemether / Lumefantrine in pregnant women.
DISTRIBUTION: Artemether / Lumefantrine treatment should only be considered if the expected benefit to the
Artemether and Lumefantrine are both highly bound to human serum proteins in vitro (95.4% mother outwieghs the risk to the fetus
and 99.9%, respectively). Artemether is well distributed throughout the body with some affinity Lactation:
for the brown fat and adrenal glands, while Lumefantrine has an affinity for adipose and glandular Artemether / Lumefantrine excretes into breast milk. It should not be taken by breast-feeding
tissue and to some extent for the lungs, spleen (due to slow elimination from lymphoid tissue) women
and bone marrow
DRUG INTERACTION:
METABOLISM: Patients who are taking any drug which inhibits the cytochrome enzyme CYP3A4 (e.g.
Artemether is rapidly and extensively metabolized in human liver microsomes to the biologically erythromycin, ketoconazole, itraconazole, cimetidine, HIV protease inhibitor, etc.)
active main metabolite dihydroartemisinin (demethylation), predominantly through the enzyme Patients who are taking any drug which is metabolized by the cytochrome enzyme CYP2D6
system CYP3A4. Lumefantrine is also metabolized by CYP3A4 in human liver microsomes, (e.g. flecainide, metoprolol, imipramine, amitryptyline, clomipramine etc.)
where glucuronidation of Lumefantrine takes place directly, after the oxidative biotransformation. STABILITY:
However, Lumafantrine inhibits the cytochrome enzyme CYP2D6 See expiry on the pack
ELIMINATION: PRESENTATION:
ARCEVA 20/120 Tablets pack of 16’s
Artemether is rapidly cleared from plasma with an elimination half-life of about 2 - 3 hours.
Lumefantrine is eliminated very slowly with a elimination half-life of 4 - 6 days in patients with
ARCEVA 40/240 Tablets pack of 8’s ( )
ARCEVA 80/480 Tablets pack of 4’s
falciparum malaria. Demographic characteristics such as sex and weight appear to have no ARCEVA 15/90mg/5ml Supension 60ml bottle
clinically releveant effects on the pharmacokinetics of Artemether / Lumefantrine. Unchanged ARCEVA 15/90mg/5ml Supension 30ml bottle
Artemether has not been detected in faeces and urine due to its rapid and high-first-pass INSTRUCTIONS:
metabolism, but several metabolites (unidentified) have been detected in both faeces and urine. Keep out of reach of children
Lumefantrine is eliminated via the bile in animals with excretion primarily in the faeces. After oral Avoid exposure to heat, light and humidity
dosing in animals qualitative and quantitative recovery of metabolites in bile and faeces was Store at 25ºC or below
relatively low, most of the dose being recovered as parent drug Improper storage may deteriorate the medicine
Manufactured by:
THERAPEUTIC INDICATION: SAMI PHARMACEUTICALS (PVT) LTD.
Artemether / Lumefantrine is indicated for the treatment of uncomplicated P.falciparum malaria F-95, S.I.T.E., Karachi-Pakistan
including multi-drug resistant strains of P.falciparum. Arceva is also effective against the blood