ARTEMETHER

Artemether for Injection 80mg/amp

 

Brand Name: Artem for Injection

 

Artemether is a lipid soluble methylether of dihydroartemisinin. Artemisinin is a novel sesquiterpene lactone, extracted from the leaves of the shrub Artemesia annua and possesses an endoperoxide bridge which is a rare feature in natural products. The endoperoxide bridge is essential for its antimalarial activity.
Its chemical formula is 3R,5aS,6R,8aS,9R,10S,12R,12aR)-Decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin. Its molecular formula is C16H26O5 and its molecular weight is 298.4.

Pharmacalogical and Toxicology

Artemether is synthetised from Artemisinin using methanol and a catalyst in hydrochloric acid medium. This results in the production of predominantly βα-artemether. The alpha-epimer is also present and causes a difficult purification of the product. The pure alpha product behaves differently and has a melting point of 100 whereas the βα-epimer has a melting point of 84-86. Both the alpha and the βα-epimers are active antimalarials.
It is the purification and separation of alpha fromβαthat leads to low yields and hence this increases the cost price of Artemether significantly.

Animal studies on acute toxicity show that the LD50 of Artemether in mice is a single i.g. administration of 895mg/kg and a single i.m. injection of 296mg/kg dose; in rats, the LD50 is a single i.m. injection of 597mg/kg dose. This proves the quite low toxicity of Artemether.

Artemether has major antimalarial properties. Chloroq-uine-resistant or multi-resistant strains of P.falciparum have a great susceptibility to Artemether. The schizont-icidal activity of Artemther is due to the destruction of the asexual erythrocytic forms of P.falciparum and P.vivax. Artemether is effective against all strains resistant to the other antimalarial agents. No cross-resistance is detected with chloroquine.

Pharmacokinetics

Pharmacokinetic data in humans are sparse, with no data demonstrating the rate or extent of absorption or the systemic distribution of artesunate. After parenteral administration, artesunate is rapidly hydrolyzed to the active metabolite dihydroartemisinin. The oral formulation is probably hydrolysed completely before entering the systemic circulation. Peak serum levels occur within one hour of an oral dose of artesunate and persist for up to 4 hours. Following intravenous administration, elimination half-life of 45 minutes has been reported. Dihydroartemisinin has a plasma elimination half-life of less than 2 hours, which may slow the development of resistance to artesunate.

Clinical Pharmacalogy

Artemether is active against all Plasmodia including those which may be resistant to other antimalarials.
Artemether has very rapid schizontocidal activity. The schizontocidal activity of artemether is mainly due to destruction of the asexual erythrocytic forms of P. falciparum and P. vivax. There is inhibition of protein synthesis during growth of trophozoites. There is no cross resistance with chloroquine.
It is not hypnozoiticidal but it reduces gametocyte carriage.
There is no rationale at present for using artemether for chemoprophylaxis.

Indication

Antimalarial drug. It is indicated for the treatment of all kinds of malarias, including the chloroquine-resistant malaria and the first aid of fata malaria.

Contraindication

Artemether is contraindicated in patients with hypersensitivity to artemether or other artemisinin compounds
Artemether is not recommended in the first trimester of pregnancy because of limited data.

Adverse Effects

Injection: Intramuscular injection. Five days course with the dose of 480mg for adults: once (80mg) daily for five consecutive days with the first dose doubled. For children, the first dose is 3.2mg/kg bodyweight, followed with 1.6mg/kg bodyweight every time from the 2nd day to 5th day.

Tablet: Oral administration. Once a day for 5 or 7 consecutive days, the dosage every time is 100mg for adults (first dose doubled). For children, the first dosage is 3.2mg/kg bodyweight, followed with 1.6mg/kg bodyweight every day.

Capsule: Oral administration. Once a day for 5 or 7 consecutive days, the dosage every time is 80mg for adults (first dose doubled). Fro children, the dosage decreases according to the age.

 

Artemether has been remarkably well-tolerated, and appears less toxic than quinine or chloroquine; adverse effects include bradycardia, electrocardiogram abnormalities, gastrointestinal disturbances (nausea, abdominal pain, diarrhoea - oral therapy only), dizziness, injection site pain, skin reactions, and fever. Transient decreases in neutrophils and reticulocytes have been reported in some patients treated with artemether.
Drug induced fever has been observed with artemether. Mild reactions were seen in patients to whom artemether had been administered intramuscularly. These included nausea, hypotension, dizziness and tinnitus. These side effects were also reported: dark urine, sweating, somnolence, and jaundice. There were no deaths or any other side effects. No irreversible side effects were seen.
Slight rise of SGOT and SGPT may occur in individual cases. Neurological side effects have not yet been observed in clinical use but clinical trials suggest that coma may be prolonged in patients treated with artemether and there was an increased incidence of convulsions in one trial in cerebral malaria. Transient first degree heart block has been documented in three patients receiving artemether.
Neurotoxicity has been observed in animal studies but not in humans.
Cardiotoxicity has been observed following administration of high doses of Artemether.

Usage and dosage

Injection: Intramuscular injection. Five days course with the dose of 480mg for adults: once (80mg) daily for five consecutive days with the first dose doubled. For children, the first dose is 3.2mg/kg bodyweight, followed with 1.6mg/kg bodyweight every time from the 2nd day to 5th day.

Overdosage

There is no experience with overdosage with artemether. There is no specific antidote known for the artemisinin derivatives.
However, experimental toxicological results obtained with large doses of artemisinin on the cardiovascular system and the CNS should be considered. Overdosage could bring on cardiac irregularities. An ECG should be taken before initiating treatment in cardiac patients. Irregularities in the pulse should be looked for and cardiac monitoring carried out if necessary. The animal results on the CNS suggest that overdose could result in changes in brain stem function. Clinicians treating cases of overdosage should look for changes in gait, loss of balance, or changes in ocular movements and reflexes.

Storage

Stored in a cool, dry, dark place.

Supply

Artemether for Injection 80mg/amp, 6 amps/box

 

Manufactured by Kunming Pharmaceutical Group, China

Distributed by Tri-Health Co. Ltd., Hong Kong

Email: TriHealth2000@yahoo.com.HK