Artesunate Injection

Here is a comprehensive overview of Artesunate Injection, with special reference to the product ARTEZEN-120 Inj by Zencus Pharma (India). Always remember: this is for educational purposes and is not a substitute for medical advice from a qualified healthcare professional.

Introduction & Mechanism of Action

Artesunate is a derivative of artemisinin (a compound from the Artemisia annua plant) used primarily for the treatment of severe malaria.

• It is favored over older drugs (e.g. quinine) in many guidelines for severe Plasmodium falciparum malaria, because of better efficacy and safety profiles.
• It acts by generating reactive oxygen species (free radicals) within the malaria parasite, damaging parasite proteins and membranes, and thereby killing the parasite.

It is important to note, however, that ar artesunate does not act on the dormant hypnozoite (liver-stage) forms of P. vivax or P. ovale. Therefore, for those species, a follow-on drug (e.g. an 8-aminoquinoline such as primaquine) is needed to prevent relapse.

 Indications & Clinical Use

 Indication

• Primary indication: Initial (parenteral) treatment of severe malaria (including in children and adults) caused by P. falciparum (and, in practice, other species too) when the patient cannot take oral therapy.
• After improvement, the patient is switched to oral antimalarial therapy to complete treatment.
• It is not used for prophylaxis (i.e. prevention) of malaria.

 Why Artesunate Over Quinine

• WHO and many national guidelines recommend parenteral artesunate over parenteral quinine for severe malaria, because artesunate has demonstrated lower mortality in clinical trials.
• It also has relatively favorable safety and tolerability compared to older drugs.

3. Dosage & Administration

3.1 Standard Dosing (Intravenous)

From U.S. prescribing information:

• 2.4 mg/kg IV at time 0, 12 hours, 24 hours
• Then once daily (2.4 mg/kg) until the patient can tolerate oral antimalarials
• Administer each dose as a slow bolus over 1–2 minutes (not continuous infusion).
• After switching to oral therapy, the parenteral form is discontinued.

WHO (and other sources) also specify similar regimens.

3.2 Preparation & Reconstitution

• The drug is supplied as a sterile powder for reconstitution with a supplied diluent (e.g. phosphate buffer) to yield a solution for injection.
• After adding the diluent, swirl gently (do not shake) until fully dissolved; inspect visually for particles.
• Use the constituted solution within 1.5 hours.
• Discard any unused portion.

3.3 Route & Setting

• Administered intravenously (IV). Intramuscular (IM) administration is less preferred, but in some settings where IV access is difficult IM may be used (though absorption is slower).
• Should be administered in a hospital or clinical setting by trained personnel, with monitoring.

3.4 Pediatric / Special Populations

• The dosing scheme is weight-based and applies to children as well as adults.
• No formal adjustment in renal or hepatic impairment has been established, though many patients with severe malaria have some organ dysfunction.
• Insufficient data in very elderly populations to define altered responses.

4. Warnings, Precautions & Safety

 Hypersensitivity / Contraindications

• Artesunate is contraindicated in individuals with known serious hypersensitivity (e.g. anaphylaxis) to artesunate.
• Monitor for signs of allergic reaction (rash, breathlessness, hypotension) during administration, and discontinue if severe reaction occurs.

 Post-Artesunate Delayed Hemolysis (PADH)

• One of the important risks is delayed hemolytic anemia, which may occur some days to weeks after treatment. Patients should be monitored (e.g., hemoglobin, markers of hemolysis) for up to 4 weeks after treatment.
• In many cases, the hemolysis is self-limited, but in some, blood transfusion may be necessary.

4.3 Bone Marrow / Reticulocytopenia

• Artesunate and related artemisinins may suppress reticulocyte production (immature red cells) transiently, but this is typically reversible after therapy cessation.

4.4 Pregnancy & Lactation

• In animal studies, artesunate exposure has shown embryotoxicity; however, severe malaria in pregnancy carries high risk, so treatment should not be delayed.
• The benefits versus potential risks must be weighed carefully.
• Dihydroartemisinin (a metabolite) is excreted into human milk; data are limited, so caution is advised.

4.5 Other Considerations & Monitoring

• Monitor renal and hepatic function (especially since severe malaria may itself impair those organs).
• Monitor for signs of hemolysis (jaundice, dark urine, drop in hemoglobin).
• Consider interaction with other drugs (e.g. strong inducers of metabolism like rifampin, carbamazepine) which might reduce artesunate levels.
• Avoid continuous infusion; use slow bolus only.

5. Adverse Effects & Safety Profile

Some of the known adverse effects include:

• Hemolytic anemia, especially delayed (post-treatment) hemolysis.
• Hypersensitivity / allergic reactions, possibly severe (anaphylaxis).
• Renal dysfunction / acute renal failure (especially in severely ill patients).
• Jaundice, hemoglobinuria (red pigments in urine) in severe cases.
• Headache, dizziness, nausea — milder side effects are possible.
• Suppression of reticulocyte count (temporary) as mentioned earlier.

Because artesunate is most often used in severe malaria (a life-threatening condition), distinguishing drug-related side effects from disease complications can be challenging.

6. Zencus Pharma & ARTEZEN-120 Inj (India)

Zencus Pharma is a pharmaceutical company based in Chandigarh, India, that produces a version of artesunate injection under the brand name ARTEZEN-120 Inj.

6.1 Product Details

• ARTEZEN-120 Inj is labeled as Artesunate 120 mg injection.
• Zencus also offers Artesunate 60 mg injection (brand ARTEZEN-60).
• The labeled use is for the initial treatment of severe malaria in both adults and pediatric patients in India.
• The product is marketed as a prescription injection (i.e. for hospital/clinical use).
• Pricing as per some listings:
    • ARTEZEN-120: ~ ₹ 425 per vial (subject to market and region)
    • ARTEZEN-60: ~ ₹ 185 per vial (as per Zencus listing)

6.2 Role & Relevance

• The existence of a locally manufactured version like ARTEZEN helps in ensuring accessibility and affordability in Indian settings, especially in resource-limited or endemic areas.
• However, one must verify that the formulation meets quality and regulatory standards, especially sterility, potency, and stability, as required by Indian pharmacopoeial norms and regulatory authorities.
• Clinicians and pharmacists using ARTEZEN must ensure dosing equivalence (i.e. mg per kg) and compatibility with known preparations and guidelines.

7. Comparative & Global Context

• The brand Amivas Artesunate for Injection (110 mg vial form) is the version approved in the U.S., with detailed FDA prescribing information.
• Globally, artesunate injections (various brands) are part of WHO’s essential medicines and are used in many malaria-endemic countries.
• The shift from quinine-based therapy to artesunate in severe malaria has been driven by strong evidence of reduced mortality and better tolerability.

8. Practical Considerations & Key Takeaways

1. Timing matters — In severe malaria, prompt initiation of parenteral therapy (e.g. artesunate) is critical to reduce morbidity and mortality.
2. Switch to oral therapy when clinically feasible, to complete full antimalarial regimen.
3. Monitor closely for hemolysis (for up to 4 weeks post-treatment), renal/liver function, allergic reactions.
4. Adjust for weight — dosing is weight based.
5. Drug interactions should be considered, especially drugs that alter metabolism or elimination.
6. Quality assurance of the injectable product is vital — including sterility, potency, correct labeling.
7. Pregnancy and pediatric use require special caution, but in life-threatening settings benefit often outweighs risk.