Common Generic Drug May Cure Ebola

January marks the 11th consecutive month of the current Ebola outbreak in West Africa. Through January 5, 2015, there have been 20,691 confirmed and suspected cases of Ebola virus disease and 8168 deaths attributed to it.¹

Although this is the largest Ebola outbreak in history and much energy and funding has been focused on the disease, a reliable treatment has not yet been developed. Several antibody-mediated, antiviral-focused, and vaccine-derived approaches are currently being investigated, but a major setback to many of these modalities is the time it takes to produce the interventions.

For example, ZMapp takes weeks to grow in a nicotine plant, and vaccines require adequate time for growth. Consequently, some investigators have turned to readily available medications that do not seem to have any antiviral activity at first glance.

One of these medications is amiodarone, a Class III antiarrhythmic agent that noncompetitively inhibits adrenergic stimulation and multiple ion channels while prolonging the action potential and refractory period in myocardial fibers.² In a 2014 in vitro study, amiodarone was found to strongly inhibit the entry of the Ebola virus and other filoviruses into host cells.³ While this process is not completely understood, the authors proposed 2 potential mechanisms for this inhibition.

The first mechanism is an accumulation of cholesterol in endosomes, similar to Niemann-Pick type C disease. Endosomes are thought to be a vital step in the virus entering host cells. The second proposed mechanism is an alteration in calcium channels, as calcium-mediated cell signaling is also thought to be required for viral entry into the host cell. The authors commented that doses used to treat cardiac arrhythmias would be adequate to inhibit viral entry.³

In the coming weeks, Sierra Leone, one of the countries hit hardest by the current Ebola outbreak, will embark on a randomized, open-label study of the addition of amiodarone to “best supportive care" comprised of fluid and electrolyte replacement, fever and pain management, prophylactic ampicillin against infection, artesunate therapy for positive cases of malaria, benzodiazepines in the cases of seizures, loperamide for diarrhea, whole blood transfusion as needed for hemorrhagic shock, and intensive supportive care for septic shock.

For patients started on amiodarone, therapy will consist of 20 mg/kg/day IV for 3 days with an initial load of 5 mg/kg during the first hour and the remaining doses infused continuously over the remainder of the day. If a patient can tolerate oral medications, the route can be changed to oral amiodarone on days 4 through 10, administering 200 mg PO 3 times daily in adults and 5 mg PO 3 times daily in children.⁴ The study authors seek to enroll 132 patients aged 2 years and older.

The results of this EASE (Emergency Amiodarone Study against Ebola) trial are eagerly awaited. Amiodarone is a readily available generic medication with oral formulations, so it can be easily deployed and administered in resource-poor countries, such as those most affected by the Ebola outbreak. While there are some concerning adverse drug reactions and interactions, any survival benefit in a disease with a predicted mortality rate of 70% would be acceptable.

Of note, there has been 1 case report of a doctor from Uganda who contracted Ebola virus disease and self-administered amiodarone prior to being transported to a treatment facility in Germany. He received 400 mg of oral amiodarone once, followed by a 1200 mg IV bolus 6 hours later, and then a continuous infusion of 1200 mg over 24 hours. However, the amiodarone was discontinued upon arrival in Germany, so it remains unclear whether the drug contributed to the doctor's survival.⁵

References

1. US Centers for Disease Control and Prevention (CDC) 2014 Ebola Outbreak in West Africa Case Counts. Available at: http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html. Accessed: January 6, 2015.

2. Cordarone (amiodarone) prescribing information. Philadelphia, PA: Pfizer, Inc; August 2014.

3. Gehrin G, Rohrmann K, Atenchong N, et al. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J Antimicrob Chemother. 2014;69:2123-31.

4. ClinicalTrials.gov. Clinical study to assess efficacy and safety of amiodarone in treating patients with Ebola virus disease (EVD) in Sierra Leone. EASE (emergency amiodarone study against Ebola). Available at: www.clinicaltrials.gov/ct2/results?term=NCT02307591. Accessed January 6, 2015.

5. Wolf T, Kann G, Becker S, et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet. http://dx.doi.org/10.1016/S0140-6736(14)62384-9.