Artesunate Amivas
Intravenous artesunate for the treatment of severe malaria in adults and children
Artesunate Amivas is an intravenous antimalarial medicine used to treat severe malaria caused by Plasmodium falciparum in adults and children of all ages. It is the WHO-recommended first-line treatment for severe malaria worldwide, having demonstrated superior efficacy over quinine in reducing mortality. Artesunate is administered as an intravenous injection in hospital settings, followed by a full course of oral antimalarial therapy once the patient can swallow medication. Each vial contains 110 mg of artesunate and is reconstituted with the supplied sodium phosphate buffer solution before use.
Quick Facts
Key Takeaways
- Artesunate Amivas is the WHO-recommended first-line treatment for severe malaria, replacing quinine due to proven mortality reduction of up to 35% in adults.
- The standard dose is 2.4 mg/kg body weight given intravenously at 0, 12, and 24 hours, then once daily until oral therapy is possible.
- Post-artesunate delayed hemolysis (PADH) can cause severe anemia weeks after treatment — blood monitoring for 4 weeks post-treatment is essential.
- Not recommended in the first trimester of pregnancy unless the benefits clearly outweigh the risks; use in later pregnancy only when no suitable alternatives exist.
- The reconstituted solution must be used within 1.5 hours of preparation and cannot be given as a continuous infusion.
What Is Artesunate Amivas and What Is It Used For?
Artesunate Amivas contains the active substance artesunate, a water-soluble derivative of artemisinin — a compound originally derived from the sweet wormwood plant (Artemisia annua), which has been used in traditional Chinese medicine for over 2,000 years. Modern pharmaceutical development has refined artesunate into a highly effective injectable treatment that acts faster against malaria parasites than any other antimalarial drug currently available.
Severe malaria is a medical emergency that occurs when infection with Plasmodium falciparum (or occasionally other Plasmodium species) leads to serious organ dysfunction. Without prompt treatment, severe malaria has a mortality rate exceeding 20%. Clinical features of severe malaria include impaired consciousness or coma (cerebral malaria), severe anemia, respiratory distress, acute kidney injury, hypoglycemia, metabolic acidosis, and shock. Children under 5 years of age in sub-Saharan Africa and non-immune travelers are at greatest risk.
The landmark SEAQUAMAT trial (2005), conducted in adults across Southeast Asia, demonstrated that intravenous artesunate reduced mortality by 35% compared to quinine. The subsequent AQUAMAT trial (2010), conducted in African children, showed a 22.5% relative reduction in mortality. Based on this Level 1A evidence, the World Health Organization (WHO) has recommended injectable artesunate as the first-line treatment for severe malaria in both adults and children since 2011.
After the initial parenteral treatment phase with Artesunate Amivas (minimum 3 intravenous doses), patients are transitioned to a full course of oral artemisinin-based combination therapy (ACT) to complete their malaria treatment. This two-stage approach ensures rapid parasite clearance during the critical acute phase followed by complete elimination of remaining parasites. Common oral follow-up regimens include artemether-lumefantrine, dihydroartemisinin-piperaquine, or atovaquone-proguanil, depending on regional resistance patterns and clinical guidelines.
Mechanism of Action
Following intravenous administration, artesunate is rapidly hydrolyzed to its active metabolite, dihydroartemisinin (DHA). Both artesunate and DHA contain an endoperoxide bridge — a chemical structure critical to their antimalarial activity. When this endoperoxide bridge comes into contact with iron-containing heme molecules inside parasitized red blood cells, it generates highly reactive free radicals (reactive oxygen species). These free radicals damage parasite proteins, lipid membranes, and cellular organelles, leading to rapid parasite death.
A key advantage of artesunate over older antimalarials is its ability to act against all blood stages of the Plasmodium parasite, including early ring-form trophozoites. This is particularly important in severe malaria, as it prevents immature parasites from maturing and sequestering in vital organs. The parasite reduction ratio of artesunate is approximately 10,000-fold per 48-hour cycle, compared to roughly 100–1,000-fold for quinine, explaining its superior clinical efficacy.
What Should You Know Before Taking Artesunate Amivas?
Contraindications
Artesunate Amivas must not be used if you have a known allergy (hypersensitivity) to:
- Artesunate or any other artemisinin-based antimalarial compound (such as artemether or dihydroartemisinin)
- Any of the other ingredients in Artesunate Amivas (listed in the composition section below)
In practice, known hypersensitivity to artemisinins is extremely rare. However, because severe malaria is a life-threatening emergency, the decision to use artesunate in patients with possible artemisinin allergy must be carefully weighed against the risk of untreated severe malaria. Healthcare providers should be prepared to manage potential allergic reactions, including anaphylaxis, in any clinical setting where artesunate is administered.
Warnings and Precautions
Following treatment with Artesunate Amivas, you may develop anemia (a decrease in red blood cells) or other changes in blood cell counts. These changes can occur during treatment but typically recover once malaria therapy is completed. However, some patients develop severe delayed anemia that may appear up to several weeks after finishing treatment. In most cases, the anemia resolves without specific treatment, but in a small number of cases it can be serious enough to require blood transfusion.
Your physician will perform regular blood tests, which may include a direct antiglobulin test (Coombs test), to determine whether treatment with corticosteroids is needed. Blood monitoring should continue for 4 weeks after completing your malaria treatment. It is essential that you attend all scheduled follow-up appointments. Discuss any concerns with your physician.
The mechanism of PADH involves the immune system recognizing and destroying previously parasitized red blood cells that survived the initial infection. Artesunate removes parasites from red blood cells (a process called “pitting”), but these “once-infected” cells are subsequently cleared by the spleen. In patients with high initial parasite loads (hyperparasitemia), this delayed clearance can lead to clinically significant hemolysis, typically peaking 7–14 days after treatment initiation.
Additional precautions include awareness that severe malaria itself causes organ dysfunction. Your medical team will monitor kidney function, liver function, blood glucose levels, and cardiac rhythm throughout your hospital stay. Artesunate contains 193 mg of sodium per single dose, which is approximately 10% of the WHO-recommended maximum daily sodium intake for adults. On days when two doses are given (12 hours apart), sodium intake from the medication reaches approximately 386 mg (about 20% of the daily limit), which may be relevant for patients on sodium-restricted diets.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, tell your physician before receiving this medicine.
First trimester: Use of Artesunate Amivas during the first trimester of pregnancy is not recommended unless the physician determines that the benefit to the mother outweighs the potential risk to the unborn child. Animal reproductive studies have shown some evidence of embryotoxicity with artemisinin derivatives, although human data are more reassuring. The WHO notes that severe malaria during pregnancy carries a very high mortality risk for both mother and fetus, which must be balanced against theoretical drug risks.
Second and third trimesters: In the later stages of pregnancy, you should only receive Artesunate Amivas if your physician considers that there are no suitable alternative medications. The WHO Guidelines for Malaria Treatment (2022) recommend artesunate in all trimesters for severe malaria when life is at risk, reflecting the clinical reality that untreated severe malaria in pregnancy has mortality rates exceeding 50%.
Breastfeeding: Trace amounts of artesunate and its metabolites may be present in breast milk. It is not known whether these concentrations affect breastfed infants. Discuss with your physician whether the benefits of breastfeeding for you and your child outweigh the potential risk. Given the short treatment duration and the rapid metabolism of artesunate, the overall exposure to the breastfed infant is expected to be minimal.
Driving and Operating Machinery
You should not drive or operate machinery if you feel tired, dizzy, or unwell. Severe malaria itself causes significant impairment of cognitive and motor function, and patients recovering from this condition should avoid driving until fully recovered and cleared by their physician.
How Does Artesunate Amivas Interact with Other Drugs?
Tell your physician about all medicines you are currently taking, have recently taken, or might take, including over-the-counter medications and herbal supplements. Drug interactions with artesunate primarily involve the cytochrome P450 enzyme system, particularly CYP2B6, CYP3A4, and UDP-glucuronosyltransferases (UGTs), which are responsible for the metabolism and elimination of artesunate and its active metabolite dihydroartemisinin.
Drugs That May Decrease Artesunate Effectiveness
The following medications are strong enzyme inducers that may accelerate the breakdown of artesunate, potentially reducing its antimalarial efficacy. Their concurrent use should be avoided or closely monitored:
| Drug | Drug Class | Interaction Mechanism | Clinical Significance |
|---|---|---|---|
| Rifampicin | Antibiotic (anti-TB) | Potent CYP3A4 and CYP2B6 inducer; accelerates artesunate metabolism | High — may cause treatment failure |
| Ritonavir | HIV protease inhibitor | Complex CYP interaction; net effect reduces DHA levels | Moderate to high |
| Nevirapine | HIV NNRTI | CYP3A4 and CYP2B6 inducer | Moderate |
| Carbamazepine | Anticonvulsant | CYP3A4 inducer; increases artesunate clearance | Moderate to high |
| Phenytoin | Anticonvulsant | CYP enzyme inducer | Moderate |
Drugs That May Increase Artesunate Levels
The following medications may inhibit the metabolism of artesunate, leading to higher blood concentrations and potentially increasing the risk of side effects:
| Drug | Drug Class | Interaction Mechanism | Clinical Significance |
|---|---|---|---|
| Diclofenac | NSAID (anti-inflammatory) | UGT inhibitor; slows DHA glucuronidation | Moderate |
| Axitinib | Tyrosine kinase inhibitor (cancer) | CYP enzyme inhibition | Moderate |
| Vandetanib | Tyrosine kinase inhibitor (cancer) | CYP enzyme inhibition | Moderate |
| Imatinib | Tyrosine kinase inhibitor (cancer) | CYP3A4 inhibitor; slows artesunate metabolism | Moderate |
Artesunate may also increase or decrease the blood levels of certain other medications. Your physician will advise you on how to take any concurrent medications during artesunate treatment. Because artesunate treatment for severe malaria is typically administered in an intensive care or high-dependency clinical setting, drug interactions are closely monitored by the medical team throughout the treatment course.
What Is the Correct Dosage of Artesunate Amivas?
Always use this medicine exactly as your physician has directed. Artesunate Amivas is administered as a slow intravenous bolus injection directly into a vein over 1–2 minutes. It must not be given as a continuous intravenous infusion. Your physician or nurse will calculate the correct dose based on your body weight and prepare and administer the injection.
Adults
Standard Adult Dosage
Dose: 2.4 mg/kg body weight per injection
Schedule:
- First dose: At time 0 (admission)
- Second dose: 12 hours after the first dose
- Third dose: 24 hours after the first dose
- Subsequent doses: Every 24 hours (once daily) until oral antimalarial therapy can be tolerated
Example: A 70 kg adult would receive 168 mg (70 × 2.4) per dose, equivalent to approximately 16.8 mL of the reconstituted solution (10 mg/mL).
The minimum treatment course is 3 intravenous doses before switching to oral therapy. If the patient remains unable to take oral medication after 3 doses, intravenous artesunate is continued once daily until oral intake is possible. Clinical evidence supports treatment with parenteral artesunate for up to 7 days if necessary, although most patients transition to oral therapy within 24–72 hours of starting treatment.
Children
Pediatric Dosage
Dose: 2.4 mg/kg body weight per injection — the same weight-based dose as adults
Schedule: Identical to the adult schedule (0, 12, 24 hours, then once daily)
Note: Artesunate Amivas is approved for use in children of all ages, including neonates. Accurate body weight measurement is critical for correct dosing in pediatric patients, particularly in young children and infants where even small dosing errors can be significant.
The AQUAMAT trial, which enrolled over 5,400 African children with severe malaria, confirmed the efficacy and safety of intravenous artesunate at 2.4 mg/kg in the pediatric population. The reduction in mortality compared to quinine was consistent across age groups, including children under 2 years of age.
Elderly Patients
No specific dose adjustment is required for elderly patients. The standard dose of 2.4 mg/kg applies regardless of age. However, elderly patients may have reduced renal and hepatic function, which should be taken into account during monitoring. Elderly travelers who develop severe malaria may have more comorbidities and concurrent medications, requiring particularly careful attention to drug interactions and organ function.
Missed Dose
Because this medicine is administered in a hospital setting, it is unlikely that a dose will be missed. If a dose is delayed for any reason, your physician or nurse will give it as soon as possible and continue the dosing schedule with subsequent doses spaced at 12 or 24-hour intervals. The treatment schedule should not be compressed to “catch up” on missed doses.
Overdose
Since Artesunate Amivas is administered under medical supervision in a hospital, overdose is unlikely. Tell your physician if you have any concerns. Signs and symptoms of artesunate overdose may include:
- Seizures (convulsions)
- Dark-colored stools
- Blood test results showing low blood cell counts (pancytopenia)
- Weakness and fatigue
- Fever
- Nausea and vomiting
There is no specific antidote for artesunate overdose. Treatment is supportive, focusing on management of symptoms and maintaining organ function. In the event of overdose, the medical team will closely monitor blood counts, kidney function, liver function, and cardiac rhythm.
Reconstitution and Administration (Healthcare Professionals)
Calculate the required dose (mg = patient weight in kg × 2.4) before reconstitution. Reconstitute only the number of vials needed for the current dose. Draw up 11 mL of the supplied 0.3 M sodium phosphate buffer and inject into the artesunate powder vial (final concentration: 10 mg/mL). Gently swirl for 5–6 minutes until fully dissolved — do not shake. Visually inspect for particles or discoloration before administration. Administer as a slow IV bolus over 1–2 minutes. The reconstituted solution must be used within 1.5 hours of preparation.
What Are the Side Effects of Artesunate Amivas?
Like all medicines, Artesunate Amivas can cause side effects, although not everybody gets them. It is important to note that many symptoms observed during treatment — such as fever, anemia, and organ dysfunction — may also be caused by severe malaria itself, making it challenging to distinguish drug side effects from disease manifestations. Your medical team will monitor you closely for any adverse effects throughout treatment and during the 4-week follow-up period.
Difficulty breathing or swallowing, swelling of the face, mouth, or throat. These are signs of a potentially serious allergic reaction (anaphylaxis). The frequency of very severe allergic reactions leading to loss of consciousness is not known.
Very Common
- Anemia (deficiency of healthy red blood cells, causing tiredness and weakness) — may occur 7 days or more, sometimes several weeks, after treatment ends
Common
- Inflammation of a vein (phlebitis) at the injection site
- Altered or unusual taste sensation
- Elevated body temperature or fever
- Very dark yellow or reddish-brown urine
- Reduced kidney function, including low urine output
- Easy bruising or slow wound healing
- Abnormal liver enzyme levels (detected in blood tests)
- Jaundice (yellowing of the skin)
- Diarrhea
- Abdominal pain
- Vomiting
- Slow heart rate (bradycardia)
- Low blood pressure (hypotension)
- Cough
- Rhinitis (nasal congestion and/or runny nose)
- Dizziness or feeling faint
- Headache
Uncommon
- Fatigue
- Nausea
- Constipation
- Pain at the injection site
- Stevens-Johnson syndrome (SJS) — painful widespread rash with blisters, especially around the mouth, nose, eyes, and genitals, with flu-like symptoms
- Loss of appetite
- Skin rash
- Itching (pruritus)
- Facial swelling and redness
- Flushing (skin redness)
Frequency Not Known
- Immune hemolytic anemia (destruction of red blood cells by the immune system)
- QT prolongation (abnormal electrical activity in the heart affecting rhythm)
Post-Artesunate Delayed Hemolysis (PADH)
Post-artesunate delayed hemolysis deserves special attention because it is the most clinically significant adverse effect unique to artesunate treatment. PADH occurs when previously parasitized red blood cells — which were “pitted” (cleaned of parasites) by the spleen but not immediately destroyed — are subsequently recognized and cleared by the immune system. This process typically begins 7–14 days after the start of treatment and can cause a significant drop in hemoglobin levels.
Risk factors for PADH include high initial parasitemia (more than 5% of red blood cells infected), higher cumulative artesunate doses, and non-immune travelers (who tend to present with higher parasite densities). The reported incidence of clinically significant PADH requiring blood transfusion ranges from 7–21% in studies of travelers with hyperparasitemic severe malaria. This is why the 4-week post-treatment blood monitoring program is essential for all patients treated with intravenous artesunate.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorized is important, as it allows continued monitoring of the medicine’s benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national medicines regulatory authority.
How Should You Store Artesunate Amivas?
Keep this medicine out of the sight and reach of children. Do not use after the expiry date stated on the label and carton after “EXP.” The expiry date refers to the last day of that month.
The unopened product (both the artesunate powder vial and the sodium phosphate buffer vial) does not require any special storage conditions. It can be stored at room temperature, which makes it practical for use in tropical and resource-limited settings where refrigeration may not be consistently available.
Once the artesunate powder has been reconstituted with the supplied buffer solution, the prepared solution must be used within 1.5 hours. This limited stability window reflects the chemical nature of artesunate in solution and is critical for maintaining drug potency. Any unused reconstituted solution should be discarded in accordance with local waste disposal guidelines. Do not save unused portions for later use.
Healthcare facilities should maintain adequate stock of Artesunate Amivas to ensure immediate availability for treating severe malaria, which is a medical emergency. Stock rotation should follow first-expiry, first-out (FEFO) principles to minimize waste.
What Does Artesunate Amivas Contain?
Active Ingredient
Each glass vial of powder contains 110 mg of artesunate.
Solvent (Buffer Solution)
Each glass vial of solvent contains 12 mL of 0.3 M sodium phosphate buffer, of which 11 mL is used for reconstitution. The buffer solution contains the following excipients:
- Monosodium phosphate monohydrate
- Disodium phosphate dihydrate
- Phosphoric acid, concentrated (for pH adjustment)
- Sodium hydroxide (for pH adjustment)
- Water for injections
After reconstitution with 11 mL of the supplied buffer, the final solution contains 10 mg artesunate per mL.
Appearance and Pack Sizes
The artesunate powder is a white or almost white, fine crystalline powder in a glass vial. The solvent is a clear, colorless liquid in a glass vial.
Each pack contains either 2 or 4 vials of Artesunate Amivas powder and 2 or 4 vials of sodium phosphate buffer solution respectively. Not all pack sizes may be marketed in every country.
Sodium Content
This medicine contains 193 mg sodium (the main component of cooking/table salt) in each single dose. This is equivalent to approximately 10% of the WHO-recommended maximum daily sodium intake for adults. Since the first and second doses are given 12 hours apart, this adds up to 386 mg sodium per day (approximately 20% of the daily limit) on days when two doses are administered.
Marketing Authorization Holder and Manufacturer
Marketing authorization holder: Amivas Ireland Ltd, Suite 5, Second Floor, Station House, Railway Square, Waterford, Ireland.
Manufacturer: MIAS Pharma Limited, Suite 1, Stafford House, Strand Road, Portmarnock, Co. Dublin, Ireland.
Frequently Asked Questions About Artesunate Amivas
Artesunate Amivas is used exclusively for the treatment of severe malaria in adults and children of all ages. Severe malaria is a life-threatening condition caused primarily by Plasmodium falciparum, characterized by organ dysfunction, impaired consciousness, severe anemia, or other serious complications. It is administered intravenously in a hospital setting, and after the acute phase, patients are transitioned to oral antimalarial therapy to complete their treatment course.
Large randomized controlled trials (SEAQUAMAT in adults and AQUAMAT in children) demonstrated that intravenous artesunate significantly reduces mortality compared to quinine. In adults, artesunate reduced mortality by approximately 35%, and in children by 22.5%. Based on this Level 1A evidence, the WHO has recommended injectable artesunate as the first-line treatment for severe malaria since 2011, replacing quinine worldwide.
Post-artesunate delayed hemolysis (PADH) is a well-recognized complication that can occur up to several weeks after completing treatment. During malaria treatment, artesunate removes parasites from red blood cells through a process called “pitting,” but these once-infected cells are subsequently cleared by the immune system, potentially causing a significant drop in hemoglobin. In patients with high initial parasite loads, this can lead to severe anemia requiring blood transfusion. Blood monitoring for 4 weeks post-treatment ensures early detection and appropriate management.
Artesunate Amivas is not recommended during the first trimester of pregnancy unless the physician determines that the benefit outweighs the risk to the unborn child. In the second and third trimesters, it should only be used if no suitable alternative treatments are available. However, severe malaria during pregnancy carries extremely high mortality for both mother and fetus, and the WHO recommends artesunate in all trimesters when life is at risk. Your physician will weigh the benefits against the potential risks in your specific situation.
Artesunate works very rapidly against malaria parasites. After intravenous administration, it is quickly converted to its active metabolite dihydroartemisinin (DHA). The parasite reduction ratio of artesunate is approximately 10,000-fold per 48-hour cycle, meaning it clears parasites from the bloodstream much faster than any other antimalarial drug. Most patients show significant clinical improvement within 24–48 hours of starting treatment, though the full treatment course must be completed with oral antimalarials.
Several medications can reduce the effectiveness of artesunate and should be used with caution or avoided: rifampicin (antibiotic for tuberculosis), ritonavir and nevirapine (HIV medications), and carbamazepine and phenytoin (anti-epileptic drugs). Additionally, diclofenac and some cancer medications (axitinib, vandetanib, imatinib) can increase artesunate levels, potentially increasing the risk of side effects. Always inform your physician about all medications you are taking.
References
- World Health Organization. WHO Guidelines for Malaria. 3rd ed. Geneva: WHO; 2022. Available from: who.int/publications/i/item/guidelines-for-malaria
- Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647-1657. doi:10.1016/S0140-6736(10)61924-1
- Dondorp A, Nosten F, Stepniewska K, et al. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial (SEAQUAMAT). Lancet. 2005;366(9487):717-725. doi:10.1016/S0140-6736(05)67176-0
- European Medicines Agency. Artesunate Amivas — Summary of Product Characteristics. Available from: ema.europa.eu/en/medicines/human/EPAR/artesunate-amivas
- Jauregui-Amezaga A, Zocco MA, Vimalesvaran S, et al. Postartesunate delayed haemolysis: a systematic review of the literature. Malar J. 2020;19(1):100. doi:10.1186/s12936-020-03174-1
- Rolling T, Agbenyega T, Krishna S, et al. Delayed haemolysis after artesunate treatment of severe malaria — review of the literature and perspective. Travel Med Infect Dis. 2015;13(2):143-149. doi:10.1016/j.tmaid.2015.03.003
- U.S. Food and Drug Administration. Artesunate for Injection — Prescribing Information. 2020. Available from: accessdata.fda.gov
- British National Formulary (BNF). Artesunate. Available from: bnf.nice.org.uk/drugs/artesunate
- World Health Organization. World Malaria Report 2023. Geneva: WHO; 2023. Available from: who.int/teams/global-malaria-programme
Medical Editorial Team
This article has been medically reviewed by the iMedic Medical Review Board, comprising specialists in infectious disease, tropical medicine, and clinical pharmacology. All clinical information follows WHO, EMA, and FDA guidelines with evidence level 1A (systematic reviews and randomized controlled trials).
Content is independently produced with no pharmaceutical industry funding. All information is evidence-based, peer-reviewed, and updated regularly according to the latest international guidelines. Our editorial process follows the iMedic Editorial Standards.
Last medical review: | Next scheduled review: