Torsunate for Injection 30 mg, 60 mg, 120 mg & 180 mg
COMPOSITION
Each vial contains
Artesunate (Sterile) 120 mg
PHARMACEUTICAL FORM: Dry Powder Injection.
PHARMACOLOGICAL PROPERTIES:
Pharmacodynamics:
Mechanism of action: Artesunate is a hemisuccinate derivative of dihydroartemisinin, which is itself formed by the reduction of artemisinin. Artemisinin is a sesquiterpene lactone endoperoxide extracted from qinghao (sweet wormwood, Artemisia annua L.), a plant which has been used for centuries in traditional Chinese medicine. The mechanism of action of the artemisinins likely involves cleavage of the internal endoperoxide bridge through reaction with haeme within the infected erythrocyte, thereby generating free radicals which alkylate vital parasite proteins. However, artemisinins have also been reported to inhibit an essential parasite calcium adenosine triphosphatase.
Pharmacokinetics:
Intravenous: After intravenous injection artesunate is very rapidly biotransformed to its active metabolite, dihydroartemisinin (DHA). Consequently, artesunate half-life (4) is estimated to be less than 5 minutes. Following a single IV dose of 2.4 mg/kg, maximum artesunate plasma concentrations (Cmax) were estimated to be 77 µmol/L in a study in Gabonese children with malaria, and 42 and 36 µmol/L in two studies in Vietnamese adults with uncomplicated malaria.
Intramuscular: Artesunate is rapidly absorbed following intramuscular injection, and peak plasma levels are generally achieved within 30 minutes of administration. Thus, after IM injection of 2.4 mg/kg of artesunate, absorption was rapid in Gabonese children and Vietnamese adults, with Tmax values of 8 and 12 minutes, respectively. The corresponding artesunate11/2 values were estimated to be 48 minutes in children and 41 minutes in adults, and Cmax values were 1.7 and 2.3µmol/L, for children and adults, respectively.
INDICATIONS: ARTESUNATE, administered intravenously or intramuscularly, is indicated for the treatment of severe malaria caused by Plasmodium falciparum, in adults and children.
POSOLOGY AND METHOD OF ADMINISTRATION:
Dose: Adults and children weighing more 20 kg or more: ARTESUNATE is administered at a dose of 2.4 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. Children weighing less than 20 kg: ARTESUNATE is administered at a dose of 3 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.
Method of administration: 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 switched to a complete treatment course of an oral combination antimalarial regimen. Relevant treatment guidelines should be consulted when selecting an appropriate regimen.
CONTRAINDICATIONS: ARTESUNATE is contraindicated in patients with hypersensitivity to artesunate or other artemisinins.
DRUG INTERACTIONS: Artesunate is rapidly and extensively converted to dihydroartemisinin (DHA), the active metabolite, primarily by plasma and erythrocyte esterases. DHA elimination is also rapid (half-life approximately 45 min) and the potential for drug-drug interactions appears limited. In vitro drug-interaction studies have demonstrated minimal effects of artesunate on cytochrome P450 isoenzymes. Few clinical drug-drug interaction studies have been performed, however no clinically significant interactions have been identified.
ADVERSE EFFECTS: The most important reported side effect of artesunate is a rare severe allergic reaction (estimated risk approximately 1 in 3000 patients), which has involved urticarial rash as well as other symptoms, including hypotension, pruritus, oedema, and/or dyspnoea. A potentially serious delayed hemolysis (Post-Artesunate Delayed Hemolysis, PADH) has been reported frequently in travellers and in children.
WARNINGS AND PRECAUTIONS:
Non-falciparum malaria: Artesunate has not been evaluated in the treatment of severe malaria due to Plasmodium vivax, Plasmodium malariae or Plasmodium ovale.
Resistance to antimalarials: Local information on the prevalence of resistance to antimalarials should be considered in choosing the appropriate combination antimalarial regimen for use with ARTESUNATE. Relevant treatment guidelines should be consulted such as those of the WHO and public health authorities.
Paediatric population: In clinical trials, the efficacy and safety of intravenous and intramuscular artesunate have been similar in adult and paediatric populations.
PREGNANCY AND LACTATION: Pregnancy: Severe malaria is especially hazardous during pregnancy, therefore full dose parenteral artesunate treatment should be administered at any stage of pregnancy without delay. Breast-feeding: Limited information indicates that dihydroartemisinin, the active metabolite of artesunate, is present at low levels in breast milk. The drug levels are not expected to cause any adverse effects in breastfed infants. The amount of drug present in breast milk does not protect the infant from malaria. Fertility: No specific studies with artesunate in humans have been conducted to evaluate effects on fertility. In a reproduction toxicity study in rats, testicular and epididymal lesions were seen, but there were no effects on fertility. The relevance of this finding for humans is unknown.
ADVERSE EFFECTS: The most important reported side effect of artesunate is a rare severe allergic reaction (estimated risk approximately 1 in 3000 patients), which has involved urticarial rash as well as other symptoms, including hypotension, pruritus, oedema, and/or dyspnoea. A potentially serious delayed hemolysis (Post-Artesunate Delayed Hemolysis, PADH) has been reported frequently in travellers and in children.
WARNINGS AND PRECAUTIONS: Non-falciparum malaria: Artesunate has not been evaluated in the treatment of severe malaria due to Plasmodium vivax, Plasmodium malariae or Plasmodium ovale. Resistance to antimalarials: Local information on the prevalence of resistance to antimalarials should be considered in choosing the appropriate combination antimalarial regimen for use with ARTESUNATE. Relevant treatment guidelines should be consulted such as those of the WHO and public health authorities. Paediatric population: In clinical trials, the efficacy and safety of intravenous and intramuscular artesunate have been similar in adult and paediatric populations.
OVERDOSE: Experience of acute overdose with artesunate is limited. A case of overdose has been documented in a 5-year-old child who was inadvertently administered rectal artesunate at a dose of 88 mg/kg/day over 4 days, representing a dose more than 7-fold higher than the highest recommended artesunate dose. The overdose was associated with pancytopenia, melena, seizures, multi-organ failure and death.
MODE OF ADMINISTRATION: IV/IM MODE OF SELLING: Prescription Only Medicine (POM). Storage: Store at a temperature not exceeding 30°C. Protect from light
PRESENTATION: A white or almost white crystalline powder filled in clear glass vial, sealed with grey butyl rubber stopper & 20 mm blue color flip-off seal.