Artesunate

Artesunate (Artesunate for Injection^TM) is FDA approved for initial treatment of severe malaria in children and adults. The CDC and WHO guidelines currently recommend IV artesunate as first-line therapy for this indication. Clinical trials have demonstrated lower in-hospital mortality when artesunate is used compared to the previous standard of care, parenteral quinine, which is no longer marketed for use in the United States. Artesunate is currently the only FDA approved drug for treatment of severe malaria in the United States.

Severe malaria equals at least one of the following:

Neurologic dysfunction (impaired consciousness, coma, seizures)
Severe anemia (Hgb <7 g/dL)
Shock
Acidosis
Disseminated intravascular coagulation (DIC)
Organ dysfunction (acute kidney injury, pulmonary edema or acute respiratory distress syndrome, jaundice + one other sign)
Blood parasite density ≥5%

For cases of severe malaria for which artesunate is being considered for treatment, infectious diseases consultation is strongly recommended.

Dosing

Initiate IV artesunate with 2.4 mg/kg/dose at 0, 12, and 24 hours. After the first 3 doses, assess a blood smear collected 4 hrs after the last dose of IV artesunate. Continue or change the treatment plan based on table below.

Treatment plan after the initial course of IV artesunate

If infection with P. vivax or P. ovale, addition of anti-relapse treatment is required with agent active against liver hypnozoites (i.e., primaquine or tafenoquine).

Treatment plan after the initial course of IV artesunate
Parasite density ≤1% and patient able to tolerate oral therapy	Transition to full treatment course with oral regimen. Oral options: artemether-lumefantrine (preferred), atovaquone-proguanil, quinine + doxycycline or clindamycin, mefloquine (if no alternatives)
Parasite density ≤1% and patient unable to tolerate oral therapy	Continue artesunate 2.4 mg/kg/dose once daily for up to 6 additional days (maximum 7 days); transition to full treatment course with an oral regimen (options above) when able.
Parasite density >1%	Continue artesunate 2.4 mg/kg/dose once daily until parasitemia ≤1% (maximum of 7 days), then transition to full treatment course with an oral regimen (options above).

Safety

Artesunate has been generally well-tolerated in clinical trials. The most common adverse events observed in patients receiving artesunate in clinical trials included acute renal failure, hemoglobinuria, jaundice, and neurological side effects (including balance impairment, confusion, tremor, and weakness); however, many of these are results of severe malaria infection and likely not related to drug therapy.

Rare cases of anaphylaxis and hemolytic anemia have been reported. Patients should be monitored for signs and symptoms of hypersensitivity to artesunate, and weekly lab monitoring should be performed in all patients treated with IV artesunate for 4 weeks post-treatment to evaluate for signs of hemolytic anemia. Labs should include hemoglobin, haptoglobin, reticulocyte count, lactate dehydrogenase (LDH), and total bilirubin.

Cost

Artesunate is available for purchase in 220mg and 440mg quantities

110mg vial cost (AWP): $5,325

Artesunate therapy estimated cost by weight of patient

Artesunate therapy estimated cost by weight of patient
Dose Information	20 kg	70 kg	100 kg
Dose	48 mg (1 vial/110mg used)	168 mg (2 vials/220mg used)	240 mg (3 vials/330mg used)
Cost per dose	$5,325	$10,650	$15,975
Cost for minimum course (24 hours)	$15,975	$31,950	$47,925
Cost for maximum course (7 days)	$47,925	$95,850	$143,775

Obtaining IV Artesunate

Artesunate is available onsite at Nebraska Medicine through a consignment program. The appropriate inpatient ID consult team and ID pharmacist on-call should be notified if therapy is being considered.

For regional external partners, Nebraska Medicine is able to make supply available for immediate transfer. Please refer to Procurement Process for Artesunate & Miltefosine for additional information.