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Wednesday, March 25, 2020


COVID-19 (CORONAVIRUS) TREATMENTS UNDER CONSIDERATION

At PBIRx, our highly experienced and educated Clinical Staff, including licensed registered pharmacists and PharmDs, have done careful research to share the following treatments that are being considered for use in the United States and/or being evaluated globally in clinical trials. It is important to note that as data continues to be collected, new treatment options will emerge.

COVID-19 (coronavirus) is a new global virus with currently no FDA approval of medications to treat infected patients or vaccines to prevent its rapid spread. However, since the virus began to infect and kill people in China in December 2019, medical professionals, including pharmaceutical manufacturers around the world, have been working to create a vaccine, while also evaluating many different drugs and combinations of drugs to treat and prevent COVID-19.  

It is important to note that all drugs have possible adverse effects and the research focuses on the possible risk of side effects versus potential efficacy in human patients. Agents being used at this time are being administered in an experimental setting under controlled conditions. No one is administered a drug for COVID-19 without a doctor’s authorization. Data on drug effectiveness and safety are collected by enrolling infected patients into clinical trials or through compassionate use as they are treated. Some of the drugs being used for COVID treatment are approved for other uses in the United States while others have only been used in other countries until now.

Treatment options often depend on many factors including age of patient, comorbidities, side effect risks, severity of coronavirus symptoms, patient specific allergies, and availability/accessibility, etc.

The first drug approved in China, or anywhere, to treat COVID-19 is Favilavir, known generically as favipiravir or under the brand name Avigan in Japan.  Avigan is an anti-viral drug that is active against RNA viruses and marketed in Japan for treatment of influenza.

According to China National Center for Biotechnology, Favilavir demonstrated an encouraging profile with mild adverse reactions in seventy (70) COVID-19 patients in a clinical trial in Shenzhen and Guangdong Provinces. The National Medical Products Administration of China has therefore approved the use of Favilavir, based on such clinical trials. Researchers noted that the drug has reportedly shown efficacy in hindering the spread and treating the disease with minimal side effects.

Favipiravir has also shown effectiveness in other reports of its treatment of COVID-19 in China. Chinese medical authorities reported positive responses in favipiravir clinical trials conducted in Wuhan and Shenzhen composed of 340 people. About 91% of infected patients treated with favipiravir showed improved lung function compared to 62% who did not receive any treatment and did not show improvement.   More significantly, those treated with favipiravir had a median of four (4) days to test negative, compared to eleven (11) days among those that did not receive treatment.  Some health officials noted that the results have not been as promising in people with a higher viral load and more severe symptoms. Favipiravir is also being developed in Japan for West Nile virus, yellow fever, and rabies.

Other drugs showing efficacy, which also do not have FDA approval in the US for COVID -19 treatment are the anti-malaria drugs hydroxychloroquine and chloroquine as well as Gilead’s experimental broad-spectrum antiviral drug remdesivir.

Hydroxychloroquine/chloroquine (brand name Plaquenil/Aralen, Resochin) are currently used in the United States and around the world to treat a variety of conditions that include malaria, lupus, and rheumatoid arthritis. Now they are being evaluated to determine if their use in COVID-19 infected patients leads to improved virological clearance and reduced mortality. President Trump announced on March 19th that the FDA has approved testing of hydroxychloroquine and chloroquine for the treatment of COVID-19 through clinical trials and “compassionate use”. Below are links to publications describing 100 patients effectively treated with chloroquine in Wuhan, ten (10) hospitals throughout China effectively treating patients with hydroxychloroquine, and twenty four (24) patients in France effectively treated with chloroquine. The results in France are not officially published yet. 

The most recently talked about and seemingly most positive of all is a new study published in the International Journal of Antimicrobial Agents. The study was conducted after reports from the treatment of Chinese patients indicated that a combination of hydroxychloroquine with a popular antibiotic shortened the duration of COVID-19infection. The new study found early evidence that the combination of hydroxychloroquine and the antibiotic azithromycin (Zithromax, Z-pack) could be especially effective in treating the virus and reducing its duration in patients. The researchers performed this study in thirty (30) confirmed COVID-19 patients comparing hydroxychloroquine on its own or in combination with azithromycin to control patients (received neither treatment). Hydroxychloroquine was effective on its own and even more effective, by a significant margin, when combined with azithromycin.  

Hydroxychloroquine eliminated the COVID virus in over fifty (50) percent of patients in 6 days while the combination eliminated the virus all patients in five (5) days.  At enrollment, six (6) patients in the study presented with no symptoms (n=6), twenty two (22) patients presented with  upper respiratory tract symptoms (sneezing, headaches and sore throats, n=22), and eight (8) patients presented with lower respiratory tract symptoms (mostly coughing, n=8).
Remdesivir a broad-spectrum nucleoside inhibitor antiviral, also known as GS-5734, has received a lot of attention in the media. Remdesivir is under investigation by Gilead Sciences for treatment of Ebola virus (a filovirus) and has shown activity against other respiratory RNA viruses like SARS-CoV and MERS-CoV. The World Health Organization (WHO) has noted Remdesivir efficacy in treating the coronavirus in China. There are now several studies ongoing to establish its safety, effectiveness and dosing against COVID-19.  Four (4) of these studies are located within the United States. Of note, currently there are concerns with its safety. GI issues and elevated liver enzymes are most notable, although this is not uncommon with other anti-viral medications.

Kaletra (lopinavir and ritonavir), a drug used to treat HIV in the United States, is being evaluated beyond its current FDA indication, for use in COVID-19. There have been reports in both China and the US of its effectiveness in treating some COVID-19 patients. It was effective in combination with chloroquine in an HCP in New Jersey who said he “would be dead and gone” if not for this treatment. Kaletra, an antiretroviral agent has formerly been shown to be effective against severe acute respiratory syndrome (SARS) in-vitro. In clinical trials, the medication is being studied alone and in combination with other anti-viral drug ribavirin and with interferon.

Below are links to guidelines from China for COVID-19 treatments, including dosing used for lopinavir/ritonavir and other antivirals such as ribavirin.

Additionally, corticosteroids are being investigated in multiple trials for the novel virus. Steroids have been and continue to be used in the treatment of other severe coronavirus infections including SARS and MERS to manage symptoms. Several alarming concerns have arisen from those uses and interim guidance from the WHO recommends against using corticosteroids in patients with COVID-19 unless they have another indication.

A potential vaccine made by Moderna in collaboration with the National Institute of Allergy and Infectious Diseases is currently being evaluated and tested in the Seattle area. Their aim is to illicit the immune system to develop antibodies against a “spike protein” found on the virus.
Johnson & Johnson, Eli Lilly and Pfizer are also actively working to develop a vaccine.

The University of Minnesota is evaluating the hypertension drug losartan to see how effective it can be to reduce the risk of organ failure for hospitalized COVID-19 patients, and if it can reduce the need for hospitalization.

Specialty drugs like Kevzara and Actemra are also being tried in new ways to treat the lung inflammation caused by COVID-19.

The WHO identifies baloxavir (brand name Xofluza), a newer medication approved for influenza in the US, also as a possible COVID treatment candidate; however, there have been supply issues since the beginning of the flu season. It is important to note that the WHO is the only institution identifying Xofluza as a potential therapeutic candidate at this time. More well known in the United States is Tamiflu (oseltamivir) which has been recommended by WHO for influenza pandemics. Tamiflu is part of a clinical trial being held in Thailand that will combine it with protease inhibitors, favipiravir, and chloroquine for treatment of COVID-19.

Lastly, many reports advising against the use of the anti-inflammatory drug ibuprofen (brand name Motrin/Advil) have come out since Olivier Veran, the French health minister, tweeted last weekend about some patients in France experiencing serious side effects. However, the European Medicines Agency issued a statement on March 18th that there is “currently no scientific evidence establishing a link between ibuprofen and worsening of COVID-19.” The World Health Organization tweeted: “Based on currently available information, WHO does not recommend against the use of ibuprofen. We are also consulting with physicians treating COVID-19 patients and are not aware of reports of any negative effects of ibuprofen, beyond the usual known side effects that limit its use in certain populations.”

In summary, at this time it remains to be determined how to most effectively treat (and hopefully soon prevent) COVID-19. The global medical community continues to work diligently to minimize the effects of COVID-19 and as new data becomes available, treatment options will inevitably continue to be updated in this rapidly evolving fluid pandemic. It is vital to keep in mind to follow the guidelines of official legitimate sources like your medical professional, the CDC and the WHO to minimize the risk and spread of this virus.









1 comment:

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