| I. Artemisinin derivatives | |
| Artesunate (preferred)¶ | Individuals ≥20 kg: 2.4 mg/kg intravenously (first dose), followed by 2.4 mg/kg at 12 and 24 hours, followed by 2.4 mg/kg once daily for 3 days or until an oral ACT drug can be administered.Δ Individuals <20 kg: 3 mg/kg intravenously (first dose), followed by 3 mg/kg at 12 and 24 hours, followed by 3 mg/kg once daily for 3 days or until an oral ACT drug can be administered.Δ |
| Artemether◊ | 3.2 mg/kg intramuscularly to the anterior thigh (first dose), followed by 1.6 mg/kg intramuscularly once daily for 3 days or until an oral ACT drug can be administered. |
| II. Quinine or quinidine§¥ | |
| Quinine dihydrochloride◊‡ | 16.7 mg base/kg (= 20 mg salt/kg) up to a maximum of 1150 mg base (1400 mg salt) in 5% dextrose loading dose over 4 hours, followed by 8.35 mg base/kg (= 10 mg salt/kg) over 4 hours at 8- or 12-hour intervals (maximum 1530 mg base/day [2100 mg salt/day]), starting 8 hours after the beginning of the loading dose. |
| Quinidine gluconate¥ | 6.25 mg base/kg (= 10 mg salt/kg) loading dose intravenously (maximum 600 mg salt) in normal saline over 1 to 2 hours, followed by 0.0125 mg base/kg/minute (= 0.02 mg salt/kg/minute) continuous infusion for at least 24 hours. |
| Alternative: 15 mg base/kg (= 24 mg salt/kg) loading dose intravenously in normal saline over 4 hours, followed by 7.5 mg base/kg (= 12 mg salt/kg) infused over 4 hours every 8 hours, starting 8 hours after the beginning of the loading dose. | |
| plus one of the following: | |
| Doxycycline† | Adults: 100 mg twice daily. Children: 2.2 mg/kg (up to 100 mg) twice daily. Doxycycline may be administered intravenously initially; switch to oral dosing once patient is able to swallow. Treatment course is 7 days. |
| Clindamycin | Adults and children: 10 mg base/kg once (maximum 900 mg) followed by 15 mg base/kg per day (maximum 1350 mg) divided into three equal doses. Clindamycin may be administered intravenously initially; switch to oral dosing once patient is able to swallow: 20 mg base/kg/day orally (maximum 1800 mg) divided into three equal doses. Treatment course is 7 days. |
ACT: artemisinin combination therapy.
* Severe malaria is a medical emergency; patients with severe malaria who cannot receive intravenous therapy immediately should receive pre-referral treatment (eg, single dose of artesunate intramuscularly in adults and children ≥6 years or artesunate rectal suppository in children <6 years); refer to the accompanying UpToDate text. Following administration of parenteral therapy (for at least 24 hours and until oral medication can be tolerated), an oral regimen should be administered. (Refer to the UpToDate table summarizing oral regimens for completion of treatment for severe malaria.)
¶ If intravenous administration is unavailable, artesunate may be administered by intramuscular injection into the anterior thigh. In the United States, intravenous artesunate was approved by the US Food and Drug Administration (FDA) in May 2020 and as of June 2021, the drug can be obtained through major drug distributors. Artesunate is unstable in solution so is dispensed as a dry powder of artesunic acid together with an ampule of diluent (5% sodium bicarbonate solution or sodium phosphate solution). The powder and liquid are mixed to provide a concentration of 10 mg/mL; the artesunate solution should be administered within one hour of preparation.
Δ For non-immune patients, parasitemia should be assessed on a blood smear collected 4 hours after last artesunate dose:For patients in endemic areas who have received at least 24 hours of parenteral therapy and are able to tolerate oral medications, treatment may be switched to oral therapy even if parasitemia is above 1%.
◊ Parenteral formulation is not available in the United States.
§ Important adverse effects include hypoglycemia, QT prolongation, tinnitus, reversible hearing loss, nausea, vomiting, dizziness, and visual disturbances. To avoid cardiotoxicity, a loading dose of quinine/quinidine should not be administered to patients who received mefloquine or other quinine derivatives within the previous 12 hours.
¥ As of April 2019 in the United States, intravenous quinidine will no longer be procured by United States hospitals. Intravenous quinine was withdrawn by the CDC as an antimalarial treatment in the 1990s, but may remain on hospital formularies for other indications.
‡ Quinine dihydrochloride should be given by rate-controlled intravenous infusion at a maximum rate of 5 mg salt/kg per hour and never by rapid intravenous injection (which can be lethal). Quinine can also be administered via intramuscular injection if intravenous infusions cannot be given: two injections of 10 mg salt/kg quinine dihydrochloride (diluted to 60 mL) should be administered four hours apart. The anterior thigh is preferred over the gluteal region to minimize the risk of sciatic nerve damage. In patients with acute kidney injury or if parenteral therapy is required for more than 48 hours in patients who are not receiving hemodialysis or hemofiltration, the dose of intravenous quinine should be reduced by one-third to one-half (eg, to 10 mg salt/kg every 12 hours or 5 mg salt/kg every 8 hours). Dose adjustments are not necessary for patients receiving hemodialysis or hemofiltration.
† Doxycycline is preferred over other tetracyclines because it does not accumulate in renal failure and has a longer half-life. Tetracycline may be used as an alternative to doxycycline (adult dosing: 250 mg orally four times daily for seven days; pediatric dosing: 6.25 mg/kg [maximum 250 mg] orally every six hours for seven days). Clindamycin is preferred to tetracyclines in pregnancy. Tetracycline antibiotics may cause permanent tooth discoloration for children <8 years if used repeatedly. However, doxycycline binds less readily to calcium than other tetracyclines and may be used for ≤21 days in children of all ages.[2]