Artesunate

What Is Artesunate?

Artesunate for Injection is an antimalarial indicated for the initial treatment of severe malaria in adult and pediatric patients. Treatment of severe malaria with Artesunate for Injection should always be followed by a complete treatment course of an appropriate oral antimalarial regimen.

What Are Side Effects of Artesunate?

Side effects of Artesunate include:

• acute kidney (renal) failure requiring dialysis,
• hemoglobin in urine (hemoglobinuria), and
• yellowing skin and eyes (jaundice)

Dosage for Artesunate

The recommended dosage of Artesunate for Injection is 2.4 mg/kg administered intravenously at 0 hours, 12 hours, and 24 hours, and thereafter administered once daily until the patient is able to tolerate oral antimalarial therapy.

Artesunate In Children

The safety and effectiveness of Artesunate for Injection for the treatment of severe malaria have been established in pediatric patients. Use of Artesunate for Injection for this indication is supported by evidence from adequate and well-controlled studies in adults and pediatric patients with additional pharmacokinetic and safety data in pediatric patients aged 6 months and older. For pediatric patients younger than 6 months of age, a pharmacokinetic (PK) extrapolation approach using modeling and simulation indicated comparable or higher predicted P K steady-state AUC of DHA between this age group and older children or adults at the recommended 2.4 mg/kg dose regimen of Artesunate for Injection. No notable safety issues were identified in limited published safety and outcome data for Artesunate for Injection in pediatric patients younger than 6 months of age with severe malaria. No dose adjustment is necessary for pediatric patients regardless of age or bodyweight.

What Drugs, Substances, or Supplements Interact with Artesunate?

Artesunate may interact with other medicines such as:

• ritonavir,
• nevirapine,
• strong UGT inducers (e.g., rifampin, carbamazepine, phenytoin), and
• UGT inhibitors (e.g., axitinib, vandetanib, imatinib, diclofenac)

Tell your doctor all medications and supplements you use.

Artesunate During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Artesunate; it may harm a fetus. However, administration of Artesunate for Injection for the treatment of severe malaria may be lifesaving for the pregnant woman and fetus. Treatment should not be delayed due to pregnancy. Artesunate passes into breast milk but it is unknown how it would affect a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Artesunate for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Artesunate Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• jaundice (yellowing of the skin or eyes);
• pale or yellowed skin, dark colored urine;
• fever, confusion or weakness; or
• kidney problems--swelling, urinating less, feeling tired or short of breath.

Common side effects may include:

• kidney problems;
• jaundice; or
• abnormal urine tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Artesunate (Artesunate)

 

Artesunate Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions observed with Artesunate for Injection are discussed in detail in the Warnings and Precautions section:

• Post-treatment Hemolysis [See WARNINGS AND PRECAUTIONS]
• Hypersensitivity [See WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to intravenous artesunate in a randomized controlled trial in patients with severe malaria in South East Asia, including 730 patients treated with intravenous artesunate (Trial 1), a supportive published randomized, controlled trial of parenteral artesunate in pediatric patients with severe malaria in Africa (Trial 2) and an uncontrolled open label study in the US in 102 patients with severe malaria treated with Artesunate for Injection (Trial 3).

In Trial 1, 730 patients received artesunate 2.4 mg/kg intravenously at 0 hours, 12 hours, 24 hours and then once daily and 730 patients received the comparator quinine as a 20 mg/kg intravenous loading dose then 10 mg/kg intravenously three times daily for treatment of severe malaria in South East Asia. The median age of patients was 28 years (range 2-87 years) and 74% were male, 14% were pediatric patients < 15 years, and 3% were pregnant females. Patients received a median of 3 doses (range 1-9 doses) of intravenous artesunate. Once able to tolerate oral therapy, patients in the artesunate arm received oral artesunate 2 mg/kg daily (not an approved route or dosing regimen) and patients in the quinine arm received oral quinine 10 mg/kg every 8 hours to complete 7 days of total therapy. A subset of patients also received oral doxycycline (100 mg twice daily for 7 days) in addition to oral artesunate or oral quinine.

In Trial 2, pediatric patients younger than 15 years of age with severe malaria in 9 African countries were treated with parenteral artesunate or parenteral quinine.

In Trial 3, 92 of 102 (90%) patients received four 2.4 mg/kg doses of artesunate intravenously at 0 hours, 12 hours, 24 hours, and 48 hours followed by oral antimalarial therapy. The median (range) age of the patients was 39 (1 to 72) years and 61% were male; 63% were African American, 25% were White, and 9% were Asian.

For Trial 1, Trial 2, and Trial 3 adverse reactions were reported during hospitalization and no post-treatment laboratory monitoring was performed.

Most Common Adverse Reactions In Trial 1

The most common adverse reactions (2% or greater) occurring more frequently in patients receiving intravenous artesunate in Trial 1 were dialysis, hemoglobinuria, and jaundice (Table 1).

Table1: : Selected Adverse Reactions Occurring in ≥2% of Patients treated for Severe Malaria in Trial 1

Adverse Reaction	Artesunate (n=730)	Quinine (n=730)1
Acute renal failure requiring dialysis2	65 (8.9%)	53 (7.3%)
Hemoglobinuria	49 (6.7%)	33 (4.5%)
Jaundice	17 (2.3%)	14 (1.9%)
1In Trial 1, 1patient randomized tothequinine arm did not receive any doses of the study drug. 2Includes the terms: dialysis, hemodialysis, and peritoneal dialysis.

Neurologic Sequelae

Patients in Trial 1 were assessed for neurologic sequelae at the time of hospital discharge. The reported neurologic sequelae included loss of balance, hemiplegia/paresis, ataxia, neuropsychiatric symptoms, tremor, generalized weakness, and confusion and restlessness. At hospital discharge, 7 patients (1%) in the artesunate arm had significant neurologic impairments compared with 3 patients (0.4%) in the quinine arm.

Adverse Reactions Reported In Trial 2

In a published randomized controlled open label trial (Trial 2) comparing parenteral artesunate 2.4 mg/kg to parenteral quinine in pediatric patients (<15 years of age) with severe malaria in Africa, the safety profile of intravenous artesunate was generally similar to that described for Trial 1 including greater incidence of neurological impairments at hospital discharge in the artesunate arm compared to the quinine arm.

Most Common Adverse Reactions In Trial 3

The most common adverse reactions in Trial 3 were anemia (65%), transaminase increase (27%), thrombocytopenia (18%), hyperbilirubinemia (14%), acute renal failure (10%), leukocytosis (10%), acute respiratory distress syndrome (8%), lymphopenia (7%), neutropenia (5%), disseminated intravascular coagulation (3%), elevated creatinine (3%), pneumonia (3%), pulmonary edema (3%), and diarrhea (3%).

Clinically Significant Adverse Reactions Reported With Artesunate For Injection In Clinical Trials For Uncomplicated Malaria (not an approved indication) And In Healthy Volunteers

The following clinically significant adverse reactions occurred in >2% of healthy volunteers or patients:

Blood and lymphatic system disorders: leukopenia, reduced reticulocyte count

Gastrointestinal disorders: abdominal pain, vomiting

General disorders and administration site conditions: pyrexia

Nervous system disorders: dysgeusia, tinnitus, dizziness, and headache

Respiratory, thoracic and mediastinal disorders: cough

Skin and subcutaneous tissue disorders: rash

The following clinically significant reactions occurred in <2% of healthy volunteers or patients:

Immune system disorders: Stevens-Johnson syndrome

Skin and subcutaneous tissue disorders: urticaria

Postmarketing Experience

The following adverse reactions have been identified during use of parenteral artesunate outside the United States. Because the reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: delayed hemolysis, immune hemolytic anemia

Gastrointestinal disorders: pancreatitis

Immune system disorders: hypersensitivity, anaphylaxis

Read the entire FDA prescribing information for Artesunate (Artesunate)