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Monday, March 30, 2020

COVID-19 Treatment Options Update


The United States has surpassed China and Italy with the highest number of novel coronavirus (COVID-19) cases. As of March 30th, the US has an estimated 149,000 confirmed cases and 2,600 deaths spanning all 50 states and the District of Columbia. The rapid surge in positive cases is a testament to how contagious the virus is and the nationwide expansion of coronavirus testing.

Medical experts, including Dr. Anthony Fauci, Director of National Institute of Allergy and Infectious Disease, anticipate the virus could become a seasonal occurrence and the most effective way to prevent future pandemics would be a vaccine, like the seasonal flu shot.  However, coronavirus vaccines will require at least 12 to 18 months of clinical study before they are approved for use.

Meanwhile, clinical trials are underway worldwide to evaluate various treatments for coronavirus infected patients to identify those that are safe and effective.  Drugs under consideration include some that are available now because they are FDA approved to treat other diseases. Therefore, the possibility of repurposing these drugs to treat COVID-19 has been a primary focus for researchers.

Avigan (favipiravir) has demonstrated promise in shortening the duration of fever and cough in patients infected with COVID-19; also known as SARS-CoV-2. More importantly, as hospital admissions increase in the US, favipiravir has been shown to reduce the need for a ventilator in a clinical trial of 200 patients in the Chinese cities of Wuhan and Shenzhen. The shortage of ventilators, required to keep people alive and breathing in severe respiratory illnesses, is a major concern in the United States.

Perhaps the most extensively discussed COVID-19 treatment candidate is hydroxychloroquine, which was approved by the FDA today as an emergency treatment for COVID-19  along with other FDA approved conditions for this drug, i.e.  lupus, rheumatoid arthritis, and malaria. By now most people have heard about the French study of hydroxychloroquine in combination with azithromycin, an antibiotic commonly known as “Z-PAK”. The results of this study are promising; however, this positive news has led to unintended consequences. Pharmacists are seeing a massive increase in hydroxychloroquine prescriptions as physicians are prescribing it off-label for themselves and family members.

In efforts to contain this potential shortage, pharmacy benefit managers such as Express Scripts and CVS Health have implemented quantity limits and fill restrictions while state pharmacy boards have issued emergency restrictions on how the drugs can be dispensed. Walgreens now has a 14-day limit for new prescriptions and a 30-day supply limit for refills of hydroxychloroquine. Furthermore, medical authorities issued a warning about self-treatment after a tragic case of poisoning where an Arizona couple in their sixties were hospitalized after ingesting a form of chloroquine sold to clean fish tanks.



Remdesivir, a drug administered only intravenously, as opposed to oral drugs chloroquine and Avigan, remains a top candidate to become one of the first antiviral drugs to gain FDA approval in the United States. Remdesivir, which was originally being developed by Gilead to treat Ebola, incorporates itself into viral RNA and prevents the virus from replicating. It has shown in laboratory studies to be more effective against coronavirus than Avigan and chloroquine. With more clinical data showing safety and efficacy, it is feasible to see it gain FDA approval. Analysts from Seeking Alpha previously reported intravenous remdesivir would only be used for severe cases of COVID-19 infection. However, after positive reports of the effectiveness of Avigan, a related antiviral drug, they now also view remdesivir as a treatment for more moderate cases. Unfortunately, the most recent development with remdesivir is that its manufacturer, Gilead Sciences, is so backed up with compassionate use requests that it is now limiting its availability to clinical trial use.

Recent weeks brought two noteworthy updates about the HIV drug Kaletra (lopinavir/ritonavir) which has been studied around the world for COVID-10 treatment. AbbVie, the manufacturer of Kaletra altruistically suspended their global patent rights to help the global community with the supply of this drug. Unfortunately, the other noteworthy update was one of disappointment. In an article in the New England Journal of Medicine, researchers reported that Kaletra failed to show a benefit in reducing mortality rates and time to clinical improvement in a clinical trial of 199 people in China. To put this result in context, it is important to note that patients were very sick and had been symptomatic for two weeks before they started the treatment. However, the authors express their opinion that Kaletra was not particularly potent against COVID-19. Kaletra has been noted to be effective in other worldwide reports and continues to be studied for treatment of COVID-19.

Specialty drugs, Kevzara and Actemra, continue to be evaluated in the role they may play in dealing with the repercussions of lung inflammation caused by the coronavirus. If fewer patients progress from needing supplemental oxygen therapy to being intubated with a ventilator, scarce resources may be better used. Researchers are postulating that the aggressive immune response to COVID-19 that leads to lung inflammation and pneumonia is caused by what is known as a cytokine storm. Another drug that has promise in modulating cytokine storm and severe pulmonary complications of COVID-19 infection is leronlimab. Two critically ill patients in New York City were taken off ventilators and out of intensive care after they received leronlimab, an experimental drug being developed for HIV and breast cancer.


Serology testing, also known as antibody testing, allows researchers to evaluate how many people have been previously exposed to the virus and able to fight it off without being symptomatic. When a person is exposed to a disease-causing agent like SARS-CoV-2, their immune system produces antibodies to fight off infection. Antibody tests require only a small blood sample, are relatively inexpensive, and can produce results in about 15 minutes. It is possible antibody testing can be used to determine who can go back to work and who needs to stay home for a 14-day quarantine before returning to work.

New York, which has the highest number of confirmed cases and casualties in the country, is conducting a trial to test how effective convalescent plasma from people who have recovered from COVID-19 can be as a treatment. This method has previously been proven to be effective during the Spanish Flu epidemic of 1918, the SARS outbreak of 2003 and the Ebola epidemic of 2013. The infusion of convalescent plasma introduces antibodies that can illicit an effective immune response and shorten the duration and severity of infection.

As the effects of COVID-19 continue to create more devastation globally, the race to find a treatment and vaccine are of the utmost importance. Ongoing clinical trials and increased testing have helped to more accurately identify the magnitude of the virus’ traumatic effects and possibly identify safe and effective ways to treat those who are infected. Until then, precautionary measures remain the best way to avoid contracting the virus.

With a larger number of infected patients worldwide comes a greater set of data which scientists are able to leverage to gain a better understanding of how the virus is spread, the progression of symptoms, and most importantly which medications may be effective to reduce the severity of symptoms and shorten the time for an infected person to recover and test negative for the virus.













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.









Thursday, February 6, 2020

Chaos at Chain Pharmacies


It’s every pharmacist’s worst nightmare…making a serious prescription error while they are rushing to fill prescriptions for waiting customers. Yet this nightmare becomes a reality all too often, even more so now than in the past, as the computer age has everyone accustomed to instant customer service. Many pharmacists believe that even one Rx error is too many.

Last Saturday the New York Times published a front page story titled:

“How Chaos at Chain Pharmacies Is Putting Patients at Risk”

In letters to state regulatory boards and in interviews with The New York Times, many pharmacists working at chain pharmacies like CVS, Rite Aid and Walgreens described understaffed and chaotic workplaces where they said it had become difficult to perform their jobs safely, putting the public at risk of medication errors. They struggle to do all of the following things, while racing to meet corporate performance metrics that they characterized as unreasonable and unsafe in an industry squeezed to do more with less:
  • Fill prescriptions
  • Administer vaccinations
  • Tend the drive-through
  • Answer phones
  • Work the cash register
  • Counsel patients
  • Call prescribers' offices
  • Call insurance companies
  • Handle inventory


Michael Jackson, chief executive of the Florida Pharmacy Association, said the number of complaints from members related to staffing cuts and worries about patient safety had become “overwhelming” in the past year. Regulating the chains can be difficult; Florida’s nine-member state pharmacy board includes a lawyer for CVS and a director of pharmacy affairs at Walgreens. Pharmacists are often afraid to speak up, fearing retaliation. The chains deny that their pharmacists are under extreme pressure, yet their bonuses are often tied to the number of prescriptions they fill and call lists completed.

CVS accounts for one-fourth of the United States’ total prescription revenue and dispenses more than 1 billion prescriptions per year; Walgreens captures about one-fifth. The chains declined to provide data about the numbers of mistakes made, and much of the information never becomes public because companies often settle with their victims out of court, requiring a confidentiality agreement. A CVS form that staff members use to report errors asks whether the patient is a “media threat”. The last study made public was in 2006; it concluded that pharmacy mistakes harm 1.5 million Americans annually.

“A fatigued and distracted pharmacist in a fast-paced, chaotic environment is much more likely to make an error. The harm from such an error ranges from being a slight inconvenience to being fatal.”
--An anonymous Texas pharmacist


What can your members do to prevent errors?

Take an active role in your health
  • Compare prescription information from your prescriber to the medication you pick up at the pharmacy/ prescriptions delivered to you (if using mail order).
  • Familiarize yourself with drug names, dose, dosage forms, and directions to help identify a possible error before it impacts your health.
  • Access pharmacy apps and digital tools where you can review your pertinent prescription history.

Ask your pharmacist
  • One of the most important responsibilities your pharmacist has is patient consultations
  • Utilize them as an expert source of information regarding your prescriptions. This allows your pharmacist to take another look to review your prescription to ensure there are no errors.

Utilize free resources
  • Carefully read and examine your prescription label; it contains information about the appearance of the tablets/capsules/liquid etc. 
  • Cross-reference that to what appears inside the vial.
  • Do not assume it is a change in manufacturer or supplier. Free websites like www.drugs.com  and www.WebMD.com  can help identify drugs.



Saturday, January 25, 2020


CORONAVIRUS AS OF JANUARY 24, 2020


When a new virus strain emerges that is not yet identified, as with the Corona Virus, it becomes known as “novel”.

In 2019, Novel Coronavirus (2019-nCoV) a virus (more specifically, a coronavirus) was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China, a city located about 500 miles from Shanghai. Early on, many of the patients in the outbreak in Wuhan reportedly had some link to a large seafood and animal market, suggesting animal-to-person spread.  However, a growing number of patients reportedly did not have exposure to animal markets, suggesting person-to-person spread is occurring. At this time it is unclear how easily this virus is spreading between people. The market closed its doors on Jan. 1, 2020.

China is rushing to build a 1,000 bed hospital in 6 days, as this virus has killed 26 people and infected about 830 more. The virus has spread to 13 provinces in China, and cases are confirmed in Thailand, South Korea, Taiwan, Vietnam, and Singapore. Two cases have now turned up in the U.S. A Washington state man in his 30s has been diagnosed after returning from a solo trip to Wuhan and a 60-year old Chicago woman who returned from Wuhan on Jan. 13th is in the hospital and is currently in stable condition and doing well. The CDC is examining 63 patients in 22 states for possible coronavirus infection.

People suspected of carrying the virus are encouraged to wear an N95 mask to prevent airborne transmission, as well as health providers who also wear personal protective gear according to the World Health Organization (WHO) guidelines.

Starting on January 17, 2020, travelers from Wuhan to the United States have been required to undergo entry screening at various airports for symptoms associated with this virus.  As of January 24, 2020 there are five U.S. airports involved in such screenings:   San Francisco, New York (JFK), Atlanta, Chicago, and Los Angeles (LAX) airports.  The “Center for Disease Control (CDC) believes the immediate risk to the U.S. public is low at this time, but the situation is evolving rapidly,” Dr. Nancy Messonnier, director of the National Center for Immunization and Respiratory Diseases, said on a conference call with reporters January 24th. Nevertheless, CDC is taking proactive preparedness precautions.

Snakes, the Chinese krait and the Chinese cobra, may be the original source of this virus. The name “Coronavirus” comes from its shape, which resembles a crown or solar corona when imaged using an electron microscope. Coronavirus is transmitted through the air. It can infect both upper and lower airways and cause severe respiratory illness and other complications in humans. Unfortunately, there is no vaccine or antiviral treatment available at this time.

This outbreak is another reminder that people should limit the consumption of wild animals to avoid zoonotic infections (infections that spread from animals to humans).