Artesunate

Registered South African indications:

• Severe malaria caused by Plasmodium falciparum

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Patients with high parasitaemia

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages
• South African Standard Treatment Guidelines indications and dosages

Infections caused by: Plasmodium falciparum

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African registered indications and dosages

Severe malaria caused by Plasmodium falciparum

• IV: Initial: 2.4mg/kg body weight, slowly over 1-2min at 0, 12 and 24hrs; Maintenance: 2.4mg/kg body weight, dly until oral treatment can be tolerated

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Severe malaria is a medical emergency and treatment should be started without any delay

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Artesunate should be administered for a minimum of 24 hours (3 doses), regardless of the patient’s ability to tolerate oral medication earlier. After at least 24 hours of artesunate, and when able to tolerate oral medication, the patient should be put on a complete treatment course with a combination of appropriate antimalarial medicines. Country-specific guidelines should be consulted when selecting an appropriate regimen

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Preparation: Due to the instability of the medicine in aqueous solutions the reconstituted solution must be used within one hour of preparation. Therefore, the required dose of artesunate should be calculated (dose in mg = patient’s weight in kg x 2.4) and the number of vials of artesunate needed should be determined prior to reconstituting the powder

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For reconstitution of artesunate solution see additional prescribing points

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Artesunate should NOT be administered as an intravenous infusion. Do not use water for injection for reconstitution of the artesunate powder or for dilution of the resulting solution prior to injection

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South African Standard Treatment Guidelines indications and dosages

Malaria - severe/complicated
- Before referral

• IM: 2.4mg/kg, immediately as a single dose and refer urgently; If referral delayed, repeat at 12hrs (2nd dose) and 24hrs (3rd dose)
  (STG, PHC 2020-23)

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Can be given by intravenous route (IV) or intramuscular route (IM). IV is the preferred route of administration. Refer to product specific professional information for guidance
IV: Slow bolus of 3-4ml/min
IM: Inject slowly. Spread dose of more than 5ml over different sites

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Water for injection is not an appropriate diluent

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For reconstitution directions see additional prescribing points

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- Treatment

• IV: Initial: 2.4mg/kg, at 0, 12 and 24hrs; Maintenance: 2.4mg/kg, dly until oral treatment can be tolerated
  (STG, Adult 2019)

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Administer at least 3 IV doses before switching to oral artemether/lumefantrine

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African registered indications and dosages
• South African Standard Treatment Guidelines indications and dosages

Infections caused by: Plasmodium falciparum

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African registered indications and dosages

Severe malaria caused by Plasmodium falciparum

• See adult dosage

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South African Standard Treatment Guidelines indications and dosages

Malaria - severe/complicated
- Before referral

• <20kg: IM: 3mg/kg, immediately as a single dose and refer urgently; If referral delayed, repeat at 12hrs (2nd dose) and 24hrs (3rd dose)
• ≥20kg: IM: 2.4mg/kg, immediately as a single dose and refer urgently; If referral delayed, repeat at 12hrs (2nd dose) and 24hrs
  (STG, PHC 2020-23)

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Can be given by intravenous route (IV) or intramuscular route (IM). IV is the preferred route of administration. Refer to product specific professional information for guidance
IV: Slow bolus of 3-4ml/min
IM: Inject slowly. Spread the dose of more than 2ml over different sites for babies

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For reconstitution directions see additional prescribing points

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- Treatment (or if repeated vomiting)

• <20kg: IV/IM: Initial: 3mg/kg, at 0, 12 and 24hrs; Maintenance: 2.4mg/kg, dly until oral treatment can be tolerated
• ≥20kg: IV/IM: Initial: 2.4mg/kg, at 0, 12 and 24hrs; Maintenance: 2.4mg/kg, dly until oral treatment can be tolerated
  (STG, Paed. 2023)

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2–3 days after initiating treatment with artesunate and patient is able to swallow, switch to any of the 2 oral regimens

Pregnancy

• Caution
• Studies in human pregnancy have shown no ill effects due to artesunate. Adverse events have been observed in some animal studies
• Use of artesunate for treatment of severe malaria during pregnancy is recommended

Breastfeeding

• Caution
• Dihydroartemisinin, the active metabolite of artesunate is excreted in breast milk at low levels. The occurrence of adverse events in breastfeeding infants is not anticipated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Anxiety
• Ataxia
• Dizziness
• Headache
• Hyperreflexia
• Metallic taste
• Restlessness
• Slurred speech

Cardiovascular Disorders

• Hypotension

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Anorexia
• Diarrhea
• Nausea and vomiting

Hepatobiliary Disorders

• Increased serum alanine aminotransferase

Genitourinary Disorders

•  Increased blood urea nitrogen

Endocrine and Metabolic Disorders

• Hypoglycemia

Musculoskeletal Disorders

• Tremor

Skin and Subcutaneous Tissue Disorders

• Erythema
• Pruritus
• Skin rash
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Haemolysis
• Neutropenia
• Reticulocytopenia
• Angioedema
• Hypersensitivity reaction

• Artemether
• CYP2A6 inducers
• CYP2A6 inhibitors
• Dapsone 
• Lumefantrine

• Full blood count
• Renal function

Reconstitution directions

South African manufacturer recommendations

• Using a syringe, withdraw the supplied sodium bicarbonate solvent from the ampoule and inject into the vial containing the artesunate powder
• Shake the vial for several minutes to mix well until the powder is completely dissolved and the solution is clear
• If the solution appears cloudy or a precipitate is present, it should be discarded
• The reconstituted artesunate solution should always be used immediately, and discarded if not used within one hour
• Following reconstitution, the solution must be diluted
• For intravenous (IV) injection: Using a syringe, add either the supplied sodium chloride 0.9% for injection solvent or the same volume of 5% glucose for injection to the vial containing the reconstituted artesunate solution. This will yield a solution containing artesunate 10mg/ml. Shake to mix well, ensuring that the resulting solution is still clear
• If the solution appears cloudy or a precipitate is present, it should be discarded. The volume required will be equal to: (desired dose in mg)/10ml Withdraw the required volume of artesunate solution from the vial with a syringe and then inject slowly intravenously, over 1-2 minutes

South African Standard Treatment Guidelines recommendations

• Reconstitute by injecting full ampoule (1ml) of bicarbonate into the vial containing the artesunate powder
• Shake until dissolved, solution will be cloudy, but will clear in approximately 2 minutes
• Discard if not clear
• After withdrawing all the air from the reconstituted vial, inject the required volume of saline (or dextrose 5%) into the reconstituted solution

Artesunate acts by cleavage of the internal endoperoxide bridge through reaction with haema within the Plasmodium falciparum-infected erythrocyte, thereby generating free radicals which alkylate vital proteins. Arterunate may also inhibit essential parasite calcium adenosine triphosphatase.

Spectrum of activity: Plasmodium falciparum

Injection (per vial) 60mg

• Garsun (Equity) originator