Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 110mg/vial
Malaria
Indicated for initial treatment of severe malaria; should always be followed by a complete treatment course of an appropriate PO antimalarial regimen
2.4 mg/kg IV at 0, 12, and 24 hr, THEN qDay until able to tolerate PO antimalarial therapy
Administer with an antimalarial agent that is active against the hypnozoite liver-stage forms of Plasmodium (eg, 8-aminoquinoline drug) to patients with severe malaria caused by P vivax or P ovale
Dosage Modifications
Renal or hepatic impairment
- No specific dosage adjustments are needed for patients with renal or hepatic impairment
- No specific pharmacokinetic studies have been carried out in patients with renal or hepatic impairment
- Most patients with severe malaria present with some degree of related renal or hepatic impairment
Dosing Considerations
Limitations of use
- Does not treat hypnozoite liver-stage forms of Plasmodium and therefore does not prevent relapses of malaria caused by P vivax or P ovale
- Concomitant therapy with an antimalarial agent (eg, 8-aminoquinoline drug) is necessary for the treatment of severe malaria caused by P vivax or P ovale
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 110mg/vial
Malaria
Indicated for initial treatment of severe malaria; should always be followed by a complete treatment course of an appropriate PO antimalarial regimen
2.4 mg/kg IV at 0, 12, and 24 hr, THEN qDay until able to tolerate PO antimalarial therapy
Administer with an antimalarial agent that is active against the hypnozoite liver-stage forms of Plasmodium (eg, 8-aminoquinoline drug) to patients with severe malaria caused by P vivax or P ovale
Dosage Modifications
Renal or hepatic impairment
- No specific dosage adjustments are needed for patients with renal or hepatic impairment
- No specific pharmacokinetic studies have been carried out in patients with renal or hepatic impairment
- Most patients with severe malaria present with some degree of related renal or hepatic impairment
Dosing Considerations
Limitations of use
- Does not treat hypnozoite liver-stage forms of Plasmodium and therefore does not prevent relapses of malaria caused by P vivax or P ovale
- Concomitant therapy with an antimalarial agent (eg, 8-aminoquinoline drug) is necessary for the treatment of severe malaria caused by P vivax or P ovale
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (3)
- dapsone topical
artesunate, dapsone topical. unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration of dapsone topical with oral dapsone or antimalarial medications because of the potential for hemolytic reactions.
- sotorasib
sotorasib will decrease the level or effect of artesunate by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- tepotinib
tepotinib will increase the level or effect of artesunate by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
Monitor Closely (19)
- axitinib
axitinib will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- berotralstat
berotralstat will increase the level or effect of artesunate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- bupivacaine implant
artesunate, bupivacaine implant. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.
- carbamazepine
carbamazepine will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.
- deferasirox
deferasirox will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- diclofenac
diclofenac will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- diflunisal
diflunisal will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- eltrombopag
eltrombopag will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- imatinib
imatinib will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- methylene blue
methylene blue will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- nevirapine
nevirapine will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA). Monitor for decreased efficacy.
- phenobarbital
phenobarbital will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.
- phenytoin
phenytoin will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.
- regorafenib
regorafenib will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- rifampin
rifampin will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.
- ritonavir
ritonavir will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA). Monitor for decreased efficacy.
- sorafenib
sorafenib will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
- tucatinib
tucatinib will increase the level or effect of artesunate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- vandetanib
vandetanib will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.
Minor (0)
Adverse Effects
>10%
Anemia (65%)
Increased transaminase (27%)
Thrombocytopenia (18%)
Hyperbilirubinemia (14%)
1-10%
Leukocytosis (10%)
Acute renal failure requiring dialysis (8.9-10%)
ARDS (8%)
Lymphopenia (7%)
Hemoglobinuria (6.7%)
Neutropenia (5%)
DIC (3%)
Elevated creatinine (3%)
Pneumonia (3%)
Pulmonary edema (3%)
Diarrhea (3%)
Jaundice (2.3%)
Neurologic sequelae (1%)
Postmarketing Reports
Blood and lymphatic system disorders: Delayed hemolysis, immune hemolytic anemia
Gastrointestinal disorders: Pancreatitis
Immune system disorders: Hypersensitivity, anaphylaxis
Acute respiratory distress syndrome
Disseminated intravascular coagulation
Warnings
Contraindications
Known serious hypersensitivity (eg, anaphylaxis)
Cautions
Hypersensitivity, including anaphylaxis, reported; consider discontinuing if hypotension, dyspnea, urticaria, or generalized rash occurs
A single IV artesunate dose is associated with embryofetal toxicity in animals; extensive experience with PO artesunate (not available) and other artemisinin drugs in pregnant women has not identified teratogenicity; delayed treatment of severe malaria is associated with serious morbidity and mortality to mother and fetus
Posttreatment hemolysis
- Post-artesunate delayed hemolysis is characterized by decreased hemoglobin with laboratory evidence of hemolysis (eg, decreased haptoglobin and increased lactate dehydrogenase) occurring at least 7 days after initiating
- Cases of posttreatment hemolytic anemia severe enough to require transfusion reported
- Monitor for 4 weeks after treatment for evidence of hemolytic anemia
- Since a subset of patients with delayed hemolysis have evidence of immune-mediated hemolysis, consider performing a direct antiglobulin test to determine if therapy (eg, corticosteroids) is necessary
Drug interaction overview
- Dihydroartemisinin (DHA), a metabolite of artesunate, is a substrate of UDP-glucuronosyltransferase (UGT) 1A9 or 2B7
- Ritonavir, nevirapine, or strong UGT inducers may reduce artesunate efficacy
- Strong UGT inhibitors may increase DHA-associated adverse reactions
Pregnancy & Lactation
Pregnancy
Pregnancy outcomes reported from a prospective surveillance study with IV artesunate are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or fetal death
Randomized controlled trials and cohort studies have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with PO artesunate (not an approved route of administration) and other artemisinin class drugs (via various routes of administration) in pregnant females over several decades
PO bioavailability is expected to be significantly lower than IV; therefore, the clinical relevance of studies involving PO exposure to artesunate and other artemisinin class drugs is uncertain
If administered during pregnancy, healthcare providers should report drug exposure by contacting Amivas LLC at 1-855-526-4827 (1-855-5AMIVAS) or www.amivas.com/our-products
Clinical considerations
Untreated malaria during pregnancy poses serious risks to the mother and fetus
Delaying treatment of severe malaria in pregnancy may result in serious morbidity and mortality to the mother and fetus
Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, severe malaria, spontaneous abortion, stillbirth, preterm delivery, low birth weight, intrauterine growth restriction, congenital malaria, and maternal and neonatal mortality
Animal studies
- A single IV administration to rats early in gestation results in embryolethality; PO administration during organogenesis in rats, rabbits, and monkeys induces a dose-dependent increase in embryolethality and fetal malformations (eg, cardiovascular, brain, skeletal) at 0.3-1.6 times the clinical dose based on BSA comparisons
- Although animal reproduction studies in several species have demonstrated fetal harm from PO and IV artesunate and other artemisinin class drugs, the clinical relevance is uncertain
Lactation
Dihydroartemisinin (DHA), a metabolite of artesunate, is present in human milk
There are no data on the effects of artesunate or DHA on breastfed infants or milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Artemisinin derivative; rapidly metabolized to active metabolite, dihydroartemisinin (DHA)
Artesunate and DHA, like other artemisinins, contain an endoperoxide bridge that is activated by heme iron leading to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and decreased parasite growth and survival
Artesunate and DHA are active against the blood-stage asexual parasites and gametocytes of Plasmodium species, including the chloroquine-resistant strains
Absorption
Peak plasma concentration
- Artesunate: 3.3 mcg/mL
- DHA: 3.1 mcg/mL
AUC
- Artesunate: 0.7 mcg⋅h/mL
- DHA: 3.5 mcg⋅h/mL
Distribution
Protein bound: ~93%
Vd
- Artesunate: 68.5 L
- DHA: 59.7 L
Metabolism
Primary pathway
- Artesunate: Blood esterases
- DHA: Glucuronidation
Metabolite
- Artesunate: DHA
- DHA: alpha-DHA-beta-glucuronide
Elimination
Excretion: Unknown
Half-life
- Artesunate: 0.3 hr
- DHA: 1.3 hr
Clearance
- Artesunate: 180 L/hr
- DHA: 32.3 L/hr
Administration
IV Preparation
Reconstitute vial contents with supplied diluent before administration
Supplied diluent consists of 12 mL of sterile 0.3 M pH 8.0 sodium phosphate buffer
Withdraw 11 mL of this diluent with a needle and syringe and inject into the artesunate vial (when constituted the final concentration of artesunate is 10 mg/mL)
Swirl gently (do not shake) for up to 5-6 minutes until powder is fully dissolved and no visible particles remain
Inspect visually for particulate matter and discoloration; do not administer if particulate matter and/or discoloration observed
Administer within 1.5 hr of reconstitution
IV Administration
Administer as slow IV bolus over 1-2 minutes
Do not administer via continuous IV infusion
Discard the vial and any unused portion of the drug product after use
Storage
Unopened vial
- Store drug and sterile diluent in the carton at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
- Do not freeze
- Avoid exposure to heat
- Keep protected from light
Reconstituted solution
- Administer within 1.5 hr following reconstitution
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
