Artesunate

Reconstitute the vial with the appropriate diluent or solvent provided. Refer to detailed product guidelines for specific instructions on reconstitution.

Patient with cardiac or gastrointestinal disease. Not indicated to treat hypnozoite liver stage forms of Plasmodium. Renal and hepatic impairment. Children. Pregnancy and lactation.

Significant: Hypersensitivity reactions (e.g. anaphylaxis, urticaria, rash, pruritus), post-treatment delayed haemolysis or haemolytic anaemia, reversible reticulocytopenia.
Blood and lymphatic system disorders: Anaemia.
Cardiac disorders: Bradycardia.
Gastrointestinal disorders: Diarrhoea, vomiting, abdominal pain, dysgeusia.
General disorders and administration site conditions: Pyrexia.
Hepatobiliary disorders: Jaundice.
Investigations: Increased ALT and AST.
Nervous system disorders: Dizziness, headache.
Renal and urinary disorders: Haemoglobinuria, acute renal failure.
Respiratory, thoracic and mediastinal disorders: Rhinitis, cough.
Vascular disorders: Hypotension, phlebitis.

Monitor Hb, reticulocyte count, haptoglobin, LDH, and total bilirubin once weekly for up to 4 weeks after initiation of treatment. Assess for signs or symptoms of hypersensitivity.

Strong UGT inhibitors (e.g. axitinib, imatinib, diclofenac, vandetanib) may increase the plasma concentration of dihydroartemisinin (DHA), the active metabolite of artesunate. Nevirapine, ritonavir, or strong UGT inducers (e.g. carbamazepine, phenytoin, rifampicin) may decrease the plasma concentration of DHA, resulting in reduced or loss of efficacy.

Description:
Mechanism of Action: Artesunate is a semisynthetic artemisinin derivative and a prodrug that is metabolised to the active metabolite, DHA. Both artesunate and DHA contain an endoperoxide bridge that is activated by haeme iron ring binding, leading to oxidative stress, protein and nucleic acid synthesis inhibition, ultrastructural changes and reduced 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 Plasmodium vivax and Plasmodium ovale.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: <1 hour (artesunate); within 15 minutes (DHA).
Distribution: Enters breast milk (DHA). Volume of distribution: 68.5 L (artesunate); 59.7 L (DHA). Plasma protein-binding: Approx 93%.
Metabolism: Rapidly hydrolysed by blood esterases into DHA, which undergoes glucuronidation.
Excretion: Via urine. Elimination half-life: 0.3 hours (artesunate); 1.3 hours (DHA).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6917864, Artesunic acid. https://pubchem.ncbi.nlm.nih.gov/compound/Artesunic-acid. Accessed Nov. 23, 2022.

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

Antimalarials

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

Anon. Artesunate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/11/2022.

Artesunate Amivas 110 mg Powder and Solvent for Solution for Injection (Amivas Ireland Ltd). MHRA. https://products.mhra.gov.uk. Accessed 04/11/2022.

Artesunate Atlantic for Injection; Artesunate Atlantic Tablets (Atlantic Laboratories Corporation Ltd). MIMS Thailand. http://www.mims.com/thailand. Accessed 04/11/2022.

Artesunate for Injection (Amivas LLC). U.S. FDA. https://www.fda.gov. Accessed 04/11/2022.

Artesunate. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 04/11/2022.

Buckingham R (ed). Artemisinin Derivatives. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2022.

WHO Guidelines for Malaria. World Health Organization. https://www.who.int. Accessed 04/11/2022.