Fluvoxamine and Ivermectin: Early treatment for COVID-19 is key to better outcomes (September 2022)

Although the vaccine rollout is greatly reducing the number of people who get seriously ill and are hospitalized with COVID-19, no vaccine offers 100% protection, and new mutations and variants of the virus such as Delta and Omicron are appearing all the time. So it's still important to find new treatments for the illness. 

In this article, we will cover 2 popular treatments i.e. Fluvoxamine and Ivermectin.
Fluvoxamine and COVID-19

Fluvoxamine 

One of them, the generic drug fluvoxamine, has shown huge potential. Developed 40 years ago as an antidepressant, fluvoxamine—sometimes known as Luvox (brand name) - has been used mainly to treat obsessive-compulsive disorder (OCD), per the National Alliance on Mental Illness (NAMI). 

TreatEarly.org

A meta-analysis of three previous trials on the drug’s effectiveness for COVID-19 treatment found “a high probability of being associated with reduced hospitalization in outpatients with COVID-19,” a study (April 2022) led by researchers from McGill University in Quebec, Canada, found.

The researchers report that fluvoxamine treatment appeared to reduce the risk of severe COVID-19 by about 25 percent if given to people at high risk for COVID-19 early in the course of their infection.

That’s significantly less effective than some current COVID-19 antiviral treatments, such as Pfizer’s antiviral pill, Paxlovid. That drug has been shown to reduce the risk of severe COVID-19 by as much as 89 percent if taken within three days after the onset of symptoms.

Still, “particularly in resource-limited settings or for individuals without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals,” fluvoxamine might provide an easily accessible alternative, the study authors write.

The fact that the drug is widely available and with a large amount of safety data is another potential benefit since it was approved by the Food and Drug Administration (FDA) in 1994. 

However, even with this meta-analysis in hand, experts say fluvoxamine is likely to be a minor tool with which to battle the COVID-19 pandemic.

Many existing drugs like the ones in C19Early.com have been used to treat COVID and often initial reports show success. However, there's concern that these studies took place before the rise of the Omicron variant of COVID-19, which has rendered certain prior treatments ineffective, such as GlaxoSmithKline’s sotrovimab. That newfound inefficacy led to the FDA revoking its emergency use authorization for the drug.

Ivermectin

Ivermectin is an anti-parasitic medication widely used in low- and middle-income countries to treat parasitic worm infections in adults and children. It’s been used for decades for this purpose by over 3.7 billion people, and is considered safe and effective. It has an increasing list of indications due to its antiviral and anti-inflammatory properties, and is included on the WHO’s Model List of Essential Medicines.

Metformin, Ivermectin, Fluvoxamine Do Not Prevent Severe COVID-19 (August 2022)

For patients with COVID-19 infection, metformin, ivermectin, and fluvoxamine do not prevent the occurrence of hypoxemia, an emergency department visit, hospitalization, or death, according to a study published in the Aug. 18 issue of the New England Journal of Medicine.

Carolyn T. Bramante, M.D., M.P.H., from the University of Minnesota in Minneapolis, and colleagues used a 2-by-3 factorial design to test the effectiveness of metformin, ivermectin, and fluvoxamine in preventing serious severe acute respiratory syndrome coronavirus 2 infection in non-hospitalized adults enrolled within three days after a confirmed diagnosis of infection and less than seven days after symptom onset. Patients were aged 30 to 85 years, and all had overweight or obesity. The primary analysis included 1,323 patients.

"None of the trial drugs resulted in a lower severity of symptoms than identically matched placebo," the authors write.

The fluvoxamine placebo tablets were donated by Apotex. The ivermectin placebo and active tablets were donated by Edenbridge. Two authors disclosed financial ties to Medtronic.

FDA Turns Down Fluvoxamine Emergency Use Authorization Request (May 2022)

The Food and Drug Administration denied an emergency use authorization for fluvoxamine as a SARS-CoV-2 antiviral. Fluvoxamine was proposed as a possible antiviral in 2021 due to its mechanisms of action for treating obsessive-compulsive disorder. These same mechanisms were suspected to inhibit SARS-CoV-2, leading to four trials testing the efficacy of the drug.

In December 2021, Dr. David R Boulware requested an emergency use authorization for the outpatient treatment of adults testing positive for SARS-CoV-2 to prevent progression to severe symptoms based on early efficacy data from the fluvoxamine trials. The Food and Drug Administration denied his request, listing concerns such as insufficient data. 

“There are effective therapeutics that are available. But not everyone has access to them. Not everyone can tolerate them. Some people have contraindications,” Boulware argued in response to the FDA rejection. “And if you go elsewhere in the world, low- and middle-income countries, they have access to no therapeutics.”

Here we will discuss the FDA’s decision and reasoning.

The FDA’s main concern was the lack of conclusive evidence from four trials that were below emergency use authorization standards. The largest of the four trials, the TOGETHER trial, was a randomized, double-blind, placebo-controlled trial of high-risk patients in Brazil. The primary endpoints of the trial were (1) emergency room visits lasting greater than six hours and (2) hospitalization due to progression of Covid-19.

The FDA found that the success of the trial was fueled by the six-hour threshold, which they found to be arbitrary. A patient remaining in the emergency room for 5.9 hours after taking fluvoxamine was considered a positive data point, whereas 6.1 hours was considered a negative. In the FDA’s words, “there are uncertainties about…whether the 6-hour timepoint represents a clinically meaningful threshold.”

The other three trials were found to be inconclusive as well. The FDA noted that the STOP COVID trial had several damaging design flaws, including a lack of randomization, a small sample size, and only a single testing center. The STOP COVID 2 trial and the COVID-OUT trial both failed to demonstrate a positive efficacy for fluvoxamine and were terminated early for futility.

While the TOGETHER trial did achieve a positive efficacy based on its trial design, the FDA ultimately concluded that the four trials failed to provide sufficient data to conclude that fluvoxamine may be an effective treatment for non-hospitalized Covid-19 patients.

The FDA’s notice of emergency use rejection for fluvoxamine was concluded with currently available and approved treatments for Covid-19. These include Paxlovid and Bebtelovimab. We note that Molnupiravir is listed among these as well, but we discourage the use of this drug due to concerns about mutagenesis and cytotoxicity (R).

Fluvoxamine and Melatonin

Both inflammation and blood clots are known to be features of severe COVID-19. Meanwhile, fluvoxamine is also known to raise melatonin, which might also help (von Bahr et al. 2000).

That said, combining fluvoxamine and melatonin may significantly increase the blood levels and effects of melatonin (Drugs.com). You can check for other potential drug interactions with fluvoxamine at Fluvoxamine Drug Interactions - Drugs.com.

As of September 2022, there are more than 15 published clinical studies of melatonin for treatment and prevention in COVID-19 and the results are promising even when it's given as a late treatment. The 2 early treatment studies provide promising evidence that melatonin was associated with an average improvement of 78%.

If you take a melatonin supplement, be careful: Too much can cause daytime sleepiness. There is no federal RDA nor any formal advice on supplement dose ranges. 

FLCCC (Front Line COVID-19 Critical Care) I-CARE Protocol

The Front Line COVID-19 Critical Care (FLCCC) Alliance was initially formed as a working group during the early COVID-19 pandemic days in response to multiple early reports of COVID patients with an inexplicably high need for prolonged mechanical ventilation and an excessive death rate. 

There are many COVID-19 treatment protocols out there on the internet. We have reviewed many protocols and believe the FLCCC I-CARE protocol is one of the practical and effective protocols to follow.

Most of the component treatments in the I-CARE protocol have various mode of actions and may not be affected by the changes in the Omicron variant spike protein.

The Front Line COVID-19 Critical Care Alliance has also developed other protocols aimed at preventionlong-haul COVID treatmentpost-vaccine recovery and hospital treatment

To find a list of physicians who follow the protocols and provide in-office and telehealth services: List of Doctors that will prescribe FLCCC protocols.



Disclaimer: Please do not consider this article as personal medical advice, but as a recommendation for use by professional providers. Consult with your trusted doctor and discuss with her/him.


Read More & References: 
The information in this article is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. We encourage readers to stay informed on news and recommendations for their own communities by using the CDCWHO, and their local public health department as resources.

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