DART^® (Adult)

Artesunate 200 mg & Amodiaquine 600 mg

Artemisinin based Combination Therapy (ACT)

DART^® (Children)

Artesunate 50 mg & Amodiaquine 200 mg

Artemisinin based Combination Therapy (ACT)

DART^® exerts it’s antimalarial effect through the synergistic activity of all its components ( Amodiaquine and Artesunate ).

Amodiaquine is a 4-aminoquinoline antimalarial with schizonticidal activity similar to chloroquine. Like chloroquine, it also possesses antipyretic and anti-inflammatory properties. It is effective against the erythrocytic stages of all four species of plasmodium (P. falciparum, P. vivax, P. ovale, P. malariae) except mature gametocytes of P. falciparum. Amodiaquine accumulates in the lysosomes of the parasites and results in loss of function. The parasite is unable to digest haemoglobin which it depends on for its energy.

Artesunate has a rapid and potent schizonticidal activity against malaria parasites. It has a peroxide bond which breaks up inside the parasite forming singlet oxygen (free radicals) which exert a direct cytotoxic effect on the cells. By virtue of this marked synergistic action, DART^® is also effective against strains that are resistant to other commonly used antimalarial drugs such as chloroquine and other 4-aminoquinoline derivatives, proguanil and sulfonamide-pyrimethamine combinations.
DART^® being an Artemisinin based combination product has marked reduction of the likelihood of resistance development to the individual components.

Amodiaquine Hydrochloride is rapidly absorbed after oral administration, it is also extensively metabolised in the liver to its pharmacologically active metabolite desethylamodiaquine, the parent compound being detectable for no longer than 8 hours. Desethylamodiaquine is concentrated in erythrocytes and is slowly eliminated with a terminal elimination half-life of up to 18 days. About 5% of the total administered dose is recovered in urine while the rest is metabolised in the body. Amodiaquine and desethylamodiaquine have been detected in the urine several months after administration. Artesunate is rapidly hydrolyzed to the active metabolite dihydro-artemisinin. Peak serum levels occur within one hour of an oral dose of Artesunate and persist for up to 4 hours. In humans, binding to plasma protein is about 50% for Artesunate. Elimination half-life of Artesunate is approximately 2 to 4 hours.

In the recommended dosage DART^® is generally well tolerated. However, the most common adverse reactions to the treatment dose of Amodiaquine are nausea, vomiting, abdominal pain, diarrhoea, itching. A less common effect is bradycardia. Amodiaquine can induce toxic hepatitis and fatal agranulocytosis following its use for malaria chemoprophylaxis. Artesunate and other related
artemisinin derivatives have been widely used in China, with no reports of any serious adverse reactions. Drug-induced fever may occur. Neurotoxicity has been observed in animal studies but not in humans. In view of the uncertainty about toxic effects, caution should be exercised when more than one 3 day treatment is given. Cardiotoxicity has been observed following administration of high doses. Possible drug related adverse effects include dizziness, itching, vomiting, abdominal pain, flatulence, headache, body ache, diarrhoea, tinnitus, increased hair loss, macular rash, reduction in neutrophil counts and convulsions. However, it is likely that many of these effects are disease related rather than drug induced. Occasional skin rash and pruritus have been observed with Artesunate.