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Artesunate: Drug information

Artesunate: Drug information
(For additional information see "Artesunate: Pediatric drug information" and see "Artesunate: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Antimalarial Agent;
  • Artemisinin Derivative
Dosing: Adult
Malaria, severe, treatment

Malaria, severe, treatment:

Note: Patients with severe malaria due to P. vivax or P. ovale should also receive an antimalarial agent active against the hypnozoite liver stage forms of Plasmodium (eg, primaquine) (Ref).

IV, IM (off-label route): 2.4 mg/kg/dose at 0 hours, 12 hours, and 24 hours. Administer additional doses once daily based on treatment recommendations (Ref).

CDC recommendations: Assess parasite density at least 4 hours after last dose of artesunate and proceed with therapy as follows, based on parasite density:

If parasitemia ≤1% and patient able to tolerate oral therapy: Transition to full treatment course with oral regimen (Ref).

If parasitemia ≤1% and patient unable to tolerate oral therapy: Continue with artesunate 2.4 mg/kg/dose once daily for up to 6 additional days. After 7 total days of IV therapy, proceed with full treatment course with an oral regimen (Ref).

If parasitemia >1%: Continue with artesunate 2.4 mg/kg/dose once daily until parasitemia ≤1% (maximum of 7 days IV treatment). Proceed with full treatment course with an oral regimen as soon as parasitemia ≤1% and patient is able to tolerate oral therapy (Ref).

WHO recommendations: After at least 24 hours of parenteral treatment, and when patient is able to tolerate oral medication, initiate a full (eg, 3 days) course of oral artemisinin-based combination therapy to complete treatment (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Artesunate: Pediatric drug information")

Malaria, treatment

Malaria (severe), treatment: Limited data available: Note: Patients with Plasmodium vivax or Plasmodium ovale should receive concomitant therapy with an antimalarial agent active against Plasmodium liver hypnozoites (eg, primaquine).

Infants, Children, and Adolescents:

<20 kg: IM, IV: 3 mg/kg/dose initially, followed by 3 mg/kg/dose at 12 hours and 24 hours; administer additional doses once daily (Ref). Note: The FDA-approved dose for this weight group is 2.4 mg/kg/dose based on pharmacokinetic modeling (Ref); however, some pharmacokinetic modeling indicates that 2.4 mg/kg/dose is inadequate to achieve similar exposure to larger weight groups; consider risks and benefits (Ref).

≥20 kg: IM, IV: 2.4 mg/kg/dose initially, followed by 2.4 mg/kg/dose at 12 hours and 24 hours. Administer additional doses once daily (Ref).

Duration:Assess parasite density 4 hours after third dose of artesunate and proceed with therapy based on result as follows (Ref):

If parasitemia ≤1% and patient able to tolerate oral therapy: Transition to oral; administer a complete oral regimen.

If parasitemia ≤1% and patient unable to tolerate oral therapy: Continue with artesunate once daily for up to 6 additional days, followed by a complete oral regimen when patient can tolerate oral therapy.

If parasitemia >1%: Continue with artesunate once daily until parasitemia ≤1%; transition to oral regimen as soon as parasitemia ≤1% and patient able to tolerate oral therapy; administer a complete oral regimen.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment necessary (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Genitourinary: Hemoglobinuria (7%)

Hepatic: Jaundice (2%)

Nervous system: Neurological signs and symptoms (1%)

Renal: Acute renal failure (9%)

Frequency not defined:

Nervous system: Ataxia, balance impairment, confusion, paresis, restlessness

Neuromuscular & skeletal: Asthenia, tremor

Postmarketing:

Hematologic & oncologic: Autoimmune hemolytic anemia, hemolysis, hemolytic anemia

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Contraindications

Hypersensitivity (eg, anaphylaxis) to artesunate or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hemolysis: Postartemisinin delayed hemolysis is characterized by a decrease in Hb with laboratory evidence of hemolysis (eg, decreased haptoglobin, increased lactate dehydrogenase) occurring ≥7 days after initiation of artesunate. Patients with higher parasite density may have a higher likelihood of delayed hemolytic anemia after treatment (CDC 2023). Cases of posttreatment hemolytic anemia severe enough to require transfusion have been reported. A subset of patients has evidence of immune-mediated hemolysis. Monitor patient for 4 weeks after treatment for evidence of hemolytic anemia; consider a direct antiglobulin test to determine if therapy for immune-mediated hemolysis is necessary.

• Hypersensitivity: Hypersensitivity, including anaphylaxis, has been reported. Monitor for signs of hypersensitivity and consider discontinuation of treatment if a reaction occurs.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Generic: 110 mg (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 110 mg (1 ea [DSC])

Generic Equivalent Available: US

Yes

Pricing: US

Solution (reconstituted) (Artesunate Intravenous)

110 mg (per each): $5,976.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Prescribing and Access Restrictions

Artesunate is commercially available in the United States. Hospital pharmacies that do not have artesunate in stock when it is needed to treat a patient with severe malaria should call Amivas (1-855-526-4827) to identify the closest distributor of artesunate for a patient emergency or call the emergency line for their drug distributor to request an emergency procurement. More information is available at https://www.cdc.gov/malaria/diagnosis_treatment/artesunate.html.

Administration: Adult

IM (off-label route): Administer by IM injection into the anterior thigh (Ref).

IV: Administer via IV bolus slowly over 1 to 2 minutes.

Administration: Pediatric

IM: Administer by IM injection into the anterior thigh (Ref).

IV: Administer IV over 1 to 2 minutes.

Use: Labeled Indications

Malaria, severe, treatment: Initial treatment of severe malaria in adult and pediatric patients.

Limitations of use: Artesunate for injection does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent relapses of malaria due to Plasmodium vivax or Plasmodium ovale. Concomitant therapy with an antimalarial agent such as an 8-aminoquinoline drug is necessary for the treatment of severe malaria due to P. vivax or P. ovale.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP2A6 (minor), P-glycoprotein/ABCB1 (minor), UGT1A9, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Artemether and Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider therapy modification

Axitinib: May increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

CarBAMazepine: May decrease serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

ChlorproMAZINE: Antimalarial Agents may increase the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy

Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification

Diclofenac (Systemic): May increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: May decrease serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Imatinib: May increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Nevirapine: May decrease serum concentrations of the active metabolite(s) of Artesunate. Nevirapine may increase the serum concentration of Artesunate. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: May decrease serum concentrations of the active metabolite(s) of Artesunate. Nirmatrelvir and Ritonavir may increase the serum concentration of Artesunate. Risk C: Monitor therapy

Primaquine: Artesunate may enhance the QTc-prolonging effect of Primaquine. Artesunate may increase the serum concentration of Primaquine. Risk C: Monitor therapy

RifAMPin: May decrease serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Ritonavir: May decrease serum concentrations of the active metabolite(s) of Artesunate. Ritonavir may increase the serum concentration of Artesunate. Risk C: Monitor therapy

Vandetanib: May increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy

Pregnancy Considerations

An increased risk of adverse pregnancy outcomes has not been observed following maternal use of artesunate.

Malaria infection during pregnancy may be more severe than in nonpregnant people and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant patients are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant patients should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2023; CDC Yellow Book 2024).

Severe malaria is life-threatening to the mother and fetus. Artesunate is recommended for the treatment of severe malaria during pregnancy regardless of trimester (CDC 2023). Consult current CDC malaria guidelines.

Data collection to monitor pregnancy and infant outcomes following exposure to artesunate is ongoing. Health care providers are encouraged to enroll patients exposed to artesunate during pregnancy in the pregnancy safety study (1-855-526-4827).

Breastfeeding Considerations

Dihydroartemisinin (DHA), the active metabolite of artesunate, can be detected in breast milk. A study (published in abstract) collected breast milk samples over 10 hours following a single maternal dose of artesunate 200 mg (postpartum age and number of samples obtained not reported). Artesunate was not measurable in breast milk (limit of detection 5 ng/mL). DHA was detected within 1 hour after the maternal dose with the highest concentration observed at 90 minutes. DHA was no longer detected 6 hours after the maternal dose. Adverse events in the breastfeeding infant would not be expected (Jansen 2006).

Artesunate is recommended for the treatment of severe malaria in patients who are breastfeeding women (WHO 2023). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Signs/symptoms of hypersensitivity; Hb, reticulocyte count, haptoglobin, lactate dehydrogenase, and total bilirubin once weekly for up to 4 weeks after artesunate initiation (CDC 2023).

Mechanism of Action

Artesunate, a semisynthetic derivative of artemisinin, is a prodrug that is rapidly metabolized to the active metabolite, dihydroartemisinin (DHA). Artesunate and DHA contain an endoperoxide bridge that is activated by heme iron binding, resulting in oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and a decrease in parasite growth and survival. Both are active against the blood-stage asexual parasites and gametocytes of Plasmodium species (including chloroquine-resistant strains) but not active against the hypnozoite liver stage forms of P. vivax and P. ovale.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: Artesunate: 68.5 L; dihydroartemisinin (DHA): 59.7 L.

Protein binding: ~93%.

Metabolism: Artesunate (prodrug) is rapidly hydrolyzed by plasma esterases to an active metabolite, DHA. DHA undergoes glucuronidation.

Half-life elimination: Artesunate: 0.3 hours; DHA: 1.3 hours.

Time to peak: DHA: Adults infected with severe malaria: Within 15 minutes (Newton 2006).

Excretion: Urine.

Clearance: Artesunate: 180 L/hour; DHA: 32.3 L/hour.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BD) Bangladesh: Arinet | Artex;
  • (BF) Burkina Faso: Artesun | Larinate;
  • (CI) Côte d'Ivoire: Artegen | Artesun | Gen m;
  • (CZ) Czech Republic: Malacef;
  • (EC) Ecuador: Artesun | Plasmotrim;
  • (EE) Estonia: Artesun;
  • (EG) Egypt: Absunate | Malari;
  • (GH) Ghana: Glunate;
  • (IE) Ireland: Artesunate amivas;
  • (IN) India: Aarnet | Afalsi | Altunate | Arkex | Artenate | Arteria | Arteross | Artfin | Artisafe | Artivil | Azunate | Calsunate | Combither at | Corother plus | Dunate | Endomal AT | Falciart | Falcigo | Falcinil | Falciquin | Falcistar | Falcynate | Famal | Fesunate | Gerinate | Glansunate | Hospisunate | Indinate | Laricide | Larinate | Larinate xp | Malnate | Match-Ar | Neosunate | Nisunate | Osonik | Pyralfin a | Rezart-s | Rt net | Rtsun | Rtsunate | Svizunate | Tesunate | Ulteria;
  • (KE) Kenya: Artesun | Dunate | Falci care | Falcinil | Gsunate | Larinate | Lysunate | M sunate | Resunate;
  • (LT) Lithuania: Rt net;
  • (MY) Malaysia: Artesun | Dunate;
  • (NG) Nigeria: Aretmed | Askasunate | Gsunate | Lever | Plasmotrim;
  • (NO) Norway: Artesun | Artesun campus | Malacef;
  • (NZ) New Zealand: Artesun;
  • (PK) Pakistan: Arcenate | Gen m | Hi sunate | Misonate;
  • (PL) Poland: Astir | Larinate;
  • (SL) Sierra Leone: Artesun | Gsunate;
  • (TH) Thailand: Plasmotrim-50;
  • (TZ) Tanzania, United Republic of: Arinate;
  • (UA) Ukraine: Malealth;
  • (UG) Uganda: Artesun | Artesunate 60mg | Falci care | Haripil | Larinate;
  • (ZA) South Africa: Garsun;
  • (ZM) Zambia: Arinate | Artesun | Falcinil | Gsunate;
  • (ZW) Zimbabwe: Artemax
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