Artemether
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Artemether
In Malaria
* Resistance
to commonly used antimalarials; need for newer and effective agents
* Qinhausou derivatives used in China for ages
* Efficacy even against parasite resistant to the antimalarials
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Chemistry
* Sesquiterpene
lactone, methyl esterified product of dihydroartemesinin
* More lipid soluble them artemesinin
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Spectrum
- Plasmodium
vivax and P. falciparium including resistant strains
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Mechanism
of Action
Active metabolite
of all artemesinin derivatives is dihydroartemesinin. Acts by
- Inhibition of protein synthesis in trophozite growth phase
- Membrane lysis of parasite cell
- Activating host immunity - Decreased adherence of RBCs
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Pharmacokinetics
* Administered
IM
* Half life = 12 hours approx
* Plasma protein binding > 75%
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Indications
* Should be
reserved for malaria unresponsive to conventional drugs
* Severe Plasmodium falciparum malaria, with brain, liver, kidney,
heart, or lung involvement
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Dosage
5 day regimen
:
Adults : 80 mg B. D. or day
1 80 mg O. D. on days 2-5
Children : 1.6 mg/kg BD on day1
1.6 mg/kg OD on days 2-5
3
day regimen :
Adults : 480 mg
Children : 9.6 mg/kg
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Adverse
Effects
* Cardiotoxicity
- bradycardia, AV block
* G. I. - Nausea, vomiting, abdominal cramps
* Reduced reticulocytes & leucocytes, increased serum transmurases
* Safety in pregnancy / lactation not established
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Drug
Interactions
* Additive
- QT Prolongation Effectwith Terfenadine, astemizole, quinidine,
disopyramide, procanamide, erythromycin, amiodarone, tricyclic antidepressants,
some phenothiazines
* Antimalarial Synergism- Tetracycline, mefloquine, primaquine
* Antagonism- Pyrimethamine, sulphadoxine
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Contraindications
* Hypersensitivity
Precautions
* Renal / Hepatic disease
* Prolonged QT interval
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Place
in Therapy
* Effective
antimalarial, for malaria unresponsive to conventional drugs
* Used in severe Plasmodium falciparum malaria, and malaria with liver,
brain, kidney, heart or lung involvement
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