Artex

Approved Indications:

• Severe malaria (including cerebral malaria), caused by Plasmodium falciparum in adults and children
• Complicated malaria when oral therapy is not feasible or effective
• Initial parenteral treatment followed by oral antimalarials

Clinically Accepted Off-label or Regional Uses:

• Malaria due to mixed infections involving P. falciparum and other Plasmodium species (e.g., P. vivax)
• Chloroquine-resistant malaria (as part of ACT—artemisinin-based combination therapy)
• Travel medicine: Emergency standby treatment for travelers to high-transmission areas (in some cases under supervision)
• Intermittent Preventive Treatment in Pregnancy (IPTp): Used in limited contexts as part of research protocols (not routine)

Adults and Children (>20 kg):

• IV route: 2.4 mg/kg at 0, 12, and 24 hours, then once daily until oral therapy is feasible (usually 2–3 days)
• IM route: Same dosage and timing as IV, when IV access is not possible

Children (<20 kg):

• IV/IM: 3.0 mg/kg at 0, 12, and 24 hours, then once daily until transition to oral therapy

Follow-up Therapy:

• After at least 24 hours of injectable artesunate and once the patient can tolerate oral medication:
• Administer a full course of ACT (e.g., artemether-lumefantrine or artesunate-amodiaquine)

Special Populations:

• Pregnancy:
• First trimester: Artesunate may be used when no safer alternatives exist; benefits outweigh risks in severe malaria.
• Second/third trimester: May be used as part of ACT.
• Renal/Hepatic Impairment: No formal dose adjustment required, but monitor organ function closely.
• Elderly: No specific adjustment; monitor for delayed clearance or adverse effects.

Administration:

• For IV use, reconstitute with sodium bicarbonate and dilute with 5% dextrose or saline; inject over 1–2 minutes.
• For IM use, inject deeply into the anterior thigh or gluteal muscle.

Artesunate is a semi-synthetic derivative of artemisinin, which acts through a rapid, potent antiplasmodial effect. It contains an endoperoxide bridge that, upon entering the parasite-infected red blood cells, is cleaved by heme or ferrous iron released from hemoglobin digestion. This cleavage produces reactive oxygen radicals, leading to parasite membrane damage, inhibition of metabolic pathways, and ultimately parasite death. Artesunate acts mainly on the ring stage and early trophozoite stages of Plasmodium falciparum, making it highly effective in reducing parasite biomass rapidly.

• Absorption: Not applicable for IV/IM formulations; rapidly bioavailable after injection.
• Distribution: Widely distributed in body fluids; crosses blood-brain barrier
• Metabolism: Rapidly hydrolyzed to active metabolite dihydroartemisinin (DHA) by plasma esterases
• Half-life:
• Artesunate: ~2–3 minutes
• DHA: ~40–60 minutes
• Excretion: Metabolites are eliminated primarily via urine and bile

Note: Despite short half-life, artesunate has a prolonged antimalarial effect due to its active metabolite and rapid parasiticidal action.

• Pregnancy:
• Previously FDA Category C (risk not ruled out)
• Current consensus (WHO & CDC): Artesunate is safe and effective in treating severe malaria in all trimesters, especially when maternal and fetal mortality risk from malaria is high
• Lactation:
• No data available on excretion into breast milk
• Due to short half-life and critical indication, breastfeeding is generally considered safe, but caution is advised
• Recommendation: Use is justified when benefits outweigh potential risks; no breastfeeding interruption typically required

• Primary Class: Antimalarial
• Subclass: Artemisinin derivative
• Category: Rapid-acting schizonticidal agent (parenteral)

• Known hypersensitivity to artesunate, artemisinin, or related derivatives
• Severe allergy to excipients (e.g., sodium bicarbonate)
• Neonates (<1 month old): Use with caution due to immature hepatic metabolism
• G6PD deficiency: Not a strict contraindication but monitor closely (especially when used with other hemolytic drugs)

• Delayed Hemolytic Anemia: Can occur up to 2–3 weeks after treatment; monitor hemoglobin weekly for 4 weeks post-treatment
• Hypersensitivity Reactions: Rash, urticaria, or anaphylaxis—rare but possible
• Neurotoxicity: Observed in animal studies at high doses; not reported in clinical settings
• Recrudescence: If not followed by ACT, incomplete parasite clearance and recurrence may occur
• Use in Pregnancy: Safe in severe cases, but routine use in uncomplicated malaria during first trimester should be avoided unless no alternatives
• Post-treatment Monitoring: Blood smears should be followed to confirm parasite clearance

Common (≥1%):

• Gastrointestinal: Nausea, vomiting, abdominal pain
• General: Dizziness, fatigue
• Injection site: Pain, inflammation (IM), phlebitis (IV)

Less Common/Rare:

• Hematologic: Delayed hemolysis (up to 2–3 weeks later), anemia
• Allergic reactions: Rash, pruritus
• Neurological: Transient hearing disturbances, headache

Serious Adverse Effects:

• Severe delayed hemolytic anemia
• Anaphylaxis (very rare)
• Hepatotoxicity (in combination therapies)

Onset: Side effects may emerge during or shortly after the treatment course; delayed hemolysis is a late-onset reaction requiring surveillance.

• Other antimalarials: Should not be used as monotherapy; combine with ACT for efficacy and resistance prevention
• Drugs affecting CYP enzymes: Minimal CYP involvement; low potential for interaction
• Enzyme-inducing agents (e.g., rifampin): May reduce artesunate efficacy by enhancing clearance
• Hematotoxic drugs (e.g., dapsone): May increase risk of hemolysis, especially in G6PD deficiency
• Vaccines: Temporary immunosuppression due to infection and artesunate may reduce vaccine effectiveness

Artesunate does not significantly inhibit or induce major CYP enzymes and has low interaction potential.

• WHO Guidelines (2023/2024):
• Artesunate is the first-line treatment for severe malaria
• Strongly preferred over quinine due to lower mortality and better safety profile
• CDC & EMA updates:
• Emphasize artesunate over quinidine in U.S. and Europe for inpatient treatment of severe malaria
• Post-treatment hemolysis warning:
• Added to global product labels to guide monitoring of anemia

• Temperature: Store vials below 25°C (77°F); avoid freezing
• Humidity: Keep in dry conditions; protect from moisture
• Light: Protect from direct sunlight
• Handling:
• Reconstituted solution should be used immediately
• If not used immediately, use within 1 hour post-reconstitution
• Do not freeze reconstituted solution
• Reconstitution: Follow manufacturer's instructions; typically reconstituted with 5% sodium bicarbonate, followed by dilution with 5% dextrose or saline for IV use