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COMPOSITION
Each vial contains:
Artesunate 60mg
The pack contains:
1ml ampoule of Sodium Bicarbonate Injection BP 5% wiv
5ml ampoule of Sodium Chloride Injection BP 0.9% w/v
DESCRIPTION
Artesunate is an antimalarial agent. It is a water-soluble hemisuccinate derivative of artemisinin. Artemisinin is a sesquiterpene lactone isolated from Artemisia annua, a herb that has traditionally been used in China for the treatment of malaria. Artesunate and its active metabolite artemisinin are potent blood schizonticides, active against the ring stage of the parasite. Artesunate is ideal for the treatment of severe malaria, including cerebral malaria. It is also active against chloroquine and mefloquine resistant strains ofP. falciparum.
Itis unstable in neutral solution and is therefore only available for injections as artesunic acid. The injectable formulation must be prepared immediately before use in 5% (w/v) sodium bicarbonate solution toproduce the salt sodium artesunate.
INDICATIONS
Injection – Treatment of severe falciparum malaria in areas where there is evidence of quinine
resistance.
Artesunate should nottobe used asa first line treatment ofmalaria.
Artesunate is not recommended for the treatment of malaria caused by P. vivax, P. ovale and P. malariae since other effective antimalarial drugs are available for this purpose.
CONTRAINDICATIONS
The drug is contraindicated in patients with prior hypersensitivity to artesunate or artemisinin
derivatives.
CLINICAL PHARMACOLOGY
Artesunate is a potent blood schizonticide agent for P. falciparum. It is effective against P.
falciparum resistant to all other antimalarial drugs. It does not have hypnozoiticidal activity. It
reduces gametocyte carriage rate.
Artesunate binds tightly to parasitized erythrocyte membranes. The functional group responsible for antimalarial activity of artesunate is endoperoxide bond. Release of an active oxygen species from this bondkills the parasite ifaccumulated in the erythrocytic cells.
It also suppresses the production or activity of antioxidant enzymes in the erythrocytes, causing lysis ofthe parasitic cell due to the highly reactive free oxygen radicals.
Artesunate has been reported to clearfeverin patients with severe falciparum malaria 16 – 25 hours after parenteraladministration.
PHARMACOKINETICS
Pharmacokinetic data in humans are sparse, with no data demonstrating the rate or extent of
absorption or the systemic distribution ofartesunate. 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.
DOSAGE AND ADMINISTRATION
Monotherapy : In those situations where the use of artemisinin combinations is impossible, for example because ofpatient intolerance to mefloquine, monotherapy with artemisinin drugs may be used in regimens of 7 days with every effort being made to ensure compliance. Administration of shorter regimens tonon-immunes patients leads to unacceptably high levels ofrecrudescence.
Dose – 4mg/Kg loading dose on thefirst dayfollowed by2mg/Kg once a dayfor6 days.
Parenteral therapy :
STEP 1: The powder for injection should be reconstituted with 1ml ofSodium Bicarbonate injection BP 5% wivand mixwell.
STEP 2: For!.V. use—Add 5 ml of Sodium Chloride Injection BP 0.9% w/v to the vial. Mix well.
For |.M. use—Add 2 mlofSodium Chloride Injection BP 0.9% w/v to thevial. Mix well.
STEP 3: For I.V. use, the required amount of the drug is administered slowly overa period of 3-4 minutes. The powder for Injection is difficulttodissolve and care should be taken to ensure that it is completely dissolved before parenteral administration. It should always be used immediately after reconstitution. Ifthe solution is cloudy or a precipitate is present, the parenteral preparation should be discarded.
Severe malaria : Arthemed is administered at a dose of2.4 mg of artesunate/kg body weight, by intravenous (IV) or intramuscular (IM) injection at 0,12 and 24 hours, then once daily until oral treatment can be substituted. Arthemed should be administered for a minimum of 24 hours (3 doses), regardless ofthe patient’s ability to tolerate oral medication earlier. After at least 24 hours of Arthemed, and when able to tolerate oral medication, the patient should beswitched toa complete treatment course ofan oral combination antimalarial regimen.
PRECAUTIONS
Parenteral artesunate should be used for the treatment of severe falciparum malaria only where there is evidence that the antimalarial efficacy of quinine is declining.
USAGE INPREGNANCY
Little experience has been gained with the use of artesunate in pregnancy, but the parenteral
preparation should not be withheld if it is considered life-saving to the mother. Oral artesunate
should not be used during thefirst trimesterofpregnancy.
DRUG INTERACTIONS
Artesunate has a minimal effect on hepatic cytochrome P450 activity and does not appear to
influence the metabolism ofmefloquine, a drug likely to be used in combination with artesunate.
Artersunate does notinhibit the formation ofcarboxy-primaquine, a metabolite ofprimaquine.
ADVERSE EFFECTS
Artesunate and other related artemisinin derivatives have been widely used in China, with no
reports of any serious adverse reactions. Drug induced fever can occur. Neurotoxicity has been observed in animal studies but not in humans. In view ofthe uncertainty about toxic effects, caution should be exercised when more than one 3-day treatment is given. Cardiotoxicity has been observed following administration ofhigh doses.
In healthy volunteers, a reversible reduction in reticulocyte counts was the dose limiting adverse effect ofartesunate, occurring with doses of 16.88mg/Kg.
Possible drug related adverse effects include dizziness, itching, vomiting, abdominal pain,
flatulence, headache, bodyache, diarrhoea, tinnitus and 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 has been observed with artesunate.
There were no clinically important local or systemic adverse effects observed in 346 patients
treated with intravenous artesunate. Electrocardiography was undertaken in a total of 82 patients.
Slight sinus bradycardia occurred in a few patients and transient first degree atrioventricular block was observed in 1 patient. Slight elevations in hepatic transaminases were also reported, but these were morelikely to be related to the diseasethanto the treatment perse.
OVERDOSAGE
No data available for overdosage of artesunate.
STORAGE:
Store below 30°C. Protect from direct sunlight.Keep all medicines outofthe reachofchildren.
