Artesunate

Severe malaria.

Adult : IV/IM Initial treatment: 2.4 mg/kg via IV bolus over 1-2 minutes or deep IM inj. Repeat after 12 hours and 24 hours then once daily thereafter. Transfer patient to an appropriate full course oral regimen after at least 24 hours of parenteral therapy and once oral medications are tolerated. Concomitant therapy with another antimalarial agent may be necessary for severe cases due to P. vivax or P. ovale. Consider local guidelines for the appropriate treatment regimen.

Parenteral
Malaria

Reconstitute vial labelled as 60 mg of artesunate with the supplied diluent. IV: Add 5 mL of 5% glucose or 0.9% NaCl inj to reconstituted solution to obtain 6 mL of artesunate solution with a concentration of 10 mg/mL. IM: Add 2 mL of 5% glucose or 0.9% NaCl inj to reconstituted solution to obtain 3 mL of artesunate solution with a concentration of 20 mg/mL. Administer within 1.5 hours after reconstitution.

Hypersensitivity to artesunate.

Patient with cardiac and gastrointestinal disease. Hepatic and renal impairment. Children. Pregnancy and lactation.

Significant: Haemolysis, severe haemolytic anaemia, hypersensitivity (including anaphylaxis).
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, taste alteration (metallic/bitter taste).
General disorders and administration site conditions: Asthenia, pancreatitis, fever, fatigue, malaise, inj site pain.
Hepatobiliary disorders: Jaundice.
Musculoskeletal and connective tissue disorders: Muscle pain, arthralgia.
Nervous system disorders: Ataxia, balance impairment, restlessness, tremor, dizziness, headache, paresis.
Psychiatric disorders: Confusion.
Renal and urinary disorders: Haemoglobinuria, acute renal failure.
Respiratory, thoracic and mediastinal disorders: Cough, nasal symptoms.
Skin and subcutaneous tissue disorders: Pruritus, rash.

Monitor for signs and symptoms of hypersensitivity and cardiotoxicity (high doses); Hb, reticulocyte count, haptoglobin, lactate dehydrogenase and total bilirubin once weekly for up to 4 weeks after treatment initiation. Monitor for evidence of haemolytic anaemia for 4 weeks after therapy. Consider performing direct antiglobulin test to determine if therapy for immune-mediated haemolysis is needed.

May decrease dihydroartemisinin (DHA) plasma concentration thus reduce efficacy of artesunate with ritonavir, nevirapine or UDP-glucuronosyltransferase (UGT) inducers (e.g. rifampicin, carbamazepine, phenytoin). May increase DHA plasma concentration thereby increase the risk of side effects with UGT inhibitors (e.g. axitinib, vandetanib, imatinib, diclofenac).

Description: Artesunate is a semisynthetic artemisinin derivative and a prodrug that is metabolised to the active metabolite dihydroartemisinin (DHA). Artesunate and DHA contain endoperoxide bridge that is activated by a heme iron ring binding leading to oxidative stress, protein and nucleic acid synthesis inhibition, ultrastructural changes and decrease in parasite growth and survival. They are active against the blood-stage asexual parasites and gametocytes of Plasmodium species including chloroquine-resistant strains but inactive against the hypnozoite liver stage forms of P. vivax and P. ovale.
Pharmacokinetics:
Absorption: Rapidly absorbed (IM). Time to peak plasma concentration: Within 15 minutes (DHA).
Distribution: Enters the breast milk (DHA). Volume of distribution: 68.5 L (artesunate); 59.7 L (DHA). Plasma protein binding: Approx 93%.
Metabolism: Rapidly hydrolysed by plasma esterases to DHA (active metabolite) which undergoes glucuronidation to form α-DHA-β-glucuronide metabolite.
Excretion: Via urine. Elimination half-life: 0.3 hours (artesunate); 1.3 hours (DHA).

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Store between 15-30°C. Protect from light.

Antimalarials

P01BE03 - artesunate ; Belongs to the class of artemisinin and derivative antimalarials.