Why is IV artesunate not FDA approved or commercially available in the United States? When will artesunate be FDA approved?

The approval process requires a pharmaceutical company to submit a New Drug Application (NDA) to FDA for approval. CDC does not have authority over NDAs or approval of new drugs. It is unknown when artesunate will be FDA-approved.

Why is artesunate not available at my hospital?

Artesunate is neither FDA approved nor commercially available for hospitals to purchase and keep in stock. CDC has made IV artesunate available through an expanded use investigational new drug protocol (IND), an FDA regulatory mechanism.

Why is artesunate only made available through the expanded use investigational new drug (IND) protocol? (What is an expanded use IND protocol?)

When availability of quinidine ends in March 2019, there will be no other FDA-approved intravenous antimalarial available in the United States. Artesunate is not FDA approved for use in the United States at this time, but it has been approved by other countries and is recommended by WHO as first-line treatment for treatment of severe malaria.

The expanded use IND is an FDA regulatory mechanism. With the unavailability of an FDA-approved intravenous antimalarial, this IND for IV artesunate allows an effective antimalarial to be available through CDC for treatment of severe malaria in the United States.

Will approval through a local institutional review board (IRB) be necessary?

This IND protocol is approved by CDC’s IRB that serves as a central IRB, consistent with FDA regulations and guidance, allowing institutions to rely on CDC’s IRB. Therefore, implementation of the treatment protocol may proceed immediately.

Hospitals that are precluded by local law or institutional policy to rely on another IRB, or that decide to perform their own IRB review, should consider the following factors: The purpose of the protocol is to provide treatment with investigational artesunate for patients with severe malaria and is subject to FDA regulations. CDC IRB has determined that the use of investigational artesunate in this IND protocol does not constitute human subjects research as defined in 45 CFR 46.102(d). Therefore, this IND protocol does not need to be reviewed for compliance with 45 CFR 46. This protocol may be used for the administration of IV artesunate to all patients with severe malaria, including vulnerable populations. Vulnerable populations including but not limited to children, pregnant and nursing women, and prisoners may be treated under this IND protocol.

As this protocol allows for administration of IV artesunate solely for treatment purposes and for non-research purposes, a Federalwide Assurance (FWA) is not required. The CDC IRB approval meets FDA regulatory requirements for IRB review.

What paperwork is involved for the artesunate release?

There is little paperwork needed prior to administration of the IV artesunate. Two documents requiring only signatures are required: 1) signed consent form, and 2) signed FDA form.

Release of the artesunate from CDC occurs as soon as possible; it does not depend on completion of the documents.

There are follow-up reporting forms to be returned to CDC after treatment is complete to fulfill FDA reporting requirements.

What are the criteria for a patient to be eligible for intravenous artesunate?

IV artesunate is indicated in a patient with a positive blood smear and severe malaria as defined by certain criteria, that is one or more of the following: Hyperparasitemia (>5%) Impaired consciousness Seizures Circulatory collapse/shock Pulmonary edema or acute respiratory distress syndrome (ARDS) Acidosis Acute renal failure Abnormal bleeding or disseminated intravascular coagulation (DIC) Jaundice (usually presents with at least one other severe criteria) Severe anemia (Hb < 7 g/dL)

IV artesunate can also be used for patients with a positive blood smear and who are unable to tolerate oral medication despite attempts to administer an oral drug.

In exceptional cases, IV artesunate can be used in a patient with strong clinical suspicion of severe malaria, for whom a timely, reliable microscopic diagnosis is not available. This indication requires consultation with a CDC malaria expert.

How do I obtain artesunate from CDC?

Clinicians with patients with severe malaria (or patients with malaria unable to tolerate oral medications) should call CDC to obtain IV artesunate. The CDC Malaria Hotline (770-488-7788) is available Monday–Friday, 9 a.m.–5 p.m., Eastern time. Outside these hours, providers should call 770-488-7100 and ask to speak with a CDC malaria expert.

Will there be delays in obtaining IV artesunate from CDC?

CDC will deliver approved artesunate releases to the airport closest to the requesting hospital. Depending on the hospital’s proximity to one of the 10 quarantine stations where artesunate is stored and timing of request, delivery times will vary. In some cases, delivery time could take up to 24 hours.

What should I do for my patient while waiting for the artesunate?

Timely delivery of artesunate is anticipated; however, severe malaria can progress rapidly. Therefore it is reasonable to administer an oral antimalarial until the artesunate arrives. For patients unable to tolerate an oral antimalarial, health care providers will need to decide the most feasible route to administer the drug.

Options may include administration of an anti-emetic prior to the antimalarial, or use of a nasogastric tube.

One dose of artemether-lumefantrine (Coartem®), atovaquone-proguanil or quinine can be administered.

If artemether-lumefantrine (Coartem ®), atovaquone-proguanil, or quinine are not available, and the health-care provider judges that immediate treatment is needed prior to the arrival of artesunate, mefloquine can be used. Note that there is a risk of severe neuropsychiatric effects at treatment doses of mefloquine.

IV clindamycin and IV tetracyclines such as doxycycline are not recommended. These drugs are slow-acting antimalarials that would not take effect until well after 24 hours, and are not effective antimalarials for treatment of severe malaria when used alone.

Can artesunate be used in children and in pregnant and lactating women?

Artesunate is safe for use in children, pregnant women in the second and third trimesters, and during lactation.

Limited clinical data on women taking artesunate in the first trimester of pregnancy have not found harmful effects. Given that severe malaria represents a substantial risk for pregnant women and their fetuses including death, and the lack of other treatment options for severe malaria in the United States, the benefits of treatment with artesunate outweigh the risks.

How will artesunate be distributed?

IV artesunate will be prepositioned at 10 quarantine stations across the United States. These quarantine stations are located at major airports based on proximity or interconnectedness to cities from where requests are most likely to originate. If, after consultation with a CDC expert, it is determined that IV artesunate is indicated, CDC will send artesunate free of charge from the quarantine station to the major airport nearest to the requesting hospital. When artesunate is sent, the requesting hospital will receive information regarding where the artesunate is coming from and time of arrival at the nearest major airport. Delivery times will vary depending on the requesting hospital’s proximity to one of the quarantine stations and flight availability.

Where will the artesunate be prepositioned? (similar questions: How is prepositioning determined?

Why only “select” quarantine stations and not all quarantine stations?)

Intravenous artesunate will be prepositioned at 10 quarantine stations across the United States. Quarantine stations are strategically selected based on their location at major airports and based on proximity and interconnectedness to cities around the country.

How long will it take for artesunate to get to my hospital?

Delivery times will vary depending on the requesting hospital’s proximity to one of the quarantine stations.