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.

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.

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.

Oral artemether is well absorbed. Artemether is hydrolyzed after administration to a biologically active metabolite, dihydroartemisinin.

Bioavailability increases in the presence of food. Total protein binding is 95.4%. The drug is rapidly and extensively metabolised in the liver.

The pharmacokinetics of artemether following oral administration appear to be similar to those for artemisinin with mean peak plasma concentrations and mean plasma half lives of 1-2 h and 2-3 h, respectively. The plasma concentrations of artemether are similar in healthy subjects and those with acute uncomplicated malaria. Plasma antimalarial activity is significantly greater with intramuscular administration than with oral use because the first-pass biotransformation is bypassed. Bioavailability of artemether following intramuscular administration was increased and clearance reduced in patients with acute renal failure.

Artemether has been reported to clear fever in severe falciparum malaria within 30 - 84 hours.

Larither is indicated for :
- Treatment of severe and complicated malaria caused by P. falciparum both in adults and children in    areas where there is multidrug resistance.

- Treatment of uncomplicated malaria in situations where there is widespread prevalence of multi-drug    resistant P. falciparum infection.

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.

1. Do not exceed the prescribed dose. In case of overdosage, urgent symptomatic treatment in a      specialized unit is required.

2. Caution is required in patients with Cardiovascular disease , Hepatic impairment , Renal insufficiency.

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.

Artemether Injection is for intramuscular use only.

3.2 mg/kg by the intramuscular route as a loading dose on the first day, followed by 1.6 mg/kg daily for a minimum of 3 days or until the patient can take oral therapy to complete a 7-day course. The daily dose can be given as a single injection. In children, the use of a tuberculin syringe is advisable since the injection volume will be small.

2.4mg/Kg intravenously on the first day followed by 1.2mg/Kg daily until the patient can take orally artesunate or another effective antimalarial drug.

Note: The speed for intravenous injection is 3-4 ml per minute.

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.

Store in a cool dry dark place.

Larither Capsules - Strip of 6 capsules.

Larither Injection - 3 x 1ml