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

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). But now, researchers are taking a closer look at how the medication could be an important treatment to prevent patients who test positive for COVID-19 from getting seriously ill with the infection.

TreatEarly.org

In 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 nonhospitalized 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, Remdesivir, Bebtelovimab, and convalescent plasma. 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 COVID-19 Early Treatment Fund

According to Steve Kirsch, Executive Director of the COVID-19 Early Treatment Fund which funded the clinical trials in the US of fluvoxamine:

1. An ounce of prevention is worth a pound of cure. Get vaccinated if possible. If you have not yet been vaccinated, taking 0.2mg/kg of ivermectin once a week has been shown to reduce the risk of getting a Covid infection by an average of 85%. It is advisable to take two doses of 0.2mg/kg spread 2 days apart in the first week.
2. Covid should be treated early and hard. A virus is like a fire and is always best treated ASAP. If your house was on fire, would you wait until the entire house was consumed by flames before you called the fire department? Of course not, you’d seek help as soon as the fire started. The biggest mistake we see is people waiting too long before seeing a doctor. They shrug off their symptoms thinking it might be a cold. If the symptoms seem like something you’ve never experienced before, it is far better to assume you have Covid and start treatment ASAP because the treatments are extremely safe and side effects are very low. Then, confirm it with a PCR test. If negative, you can stop treatment. However, if you have a loss of taste or smell or any symptom that is unique to Covid, it is safest to assume you have Covid even if your test is negative (since the tests are not 100% accurate). It took 14 years from the first case of HIV before David Ho wrote his famous editorial that HIV should be treated early and hard. Let’s not make the same mistake with this virus. “Early” means you want to start treatment as soon as you know or strongly suspect you have Covid, ideally before you develop symptoms (i.e., start treating after a positive test).“Hard” means hitting the virus simultaneously with at least an antiviral and anti-inflammatory drug combination. This approach has been proven successful in thousands of patients. The earlier you treat, the better the outcomes. If you wait five days after experiencing symptoms before being treated, your chance of being hospitalized can rise from zero to 10% or more. The only hospitalizations we’ve seen in practice are when the patient waits too long before seeing his or her doctor, can’t get a prescription filled in a timely manner, doesn’t take the drug, or the drug quality is an issue. The first two are the most common.
3. The combination of ivermectin and fluvoxamine is extremely effective when used ASAP. Two of the most effective drugs to treat Covid early are ivermectin and fluvoxamine. Both drugs should be started together at the same time. If you are treated within 48 hours of first symptoms, research shows that ivermectin should be given at a dose of 0.4mg/kg for a minimum of 5 days or until symptoms resolve, whichever is later. Fluvoxamine should be given as 50 mg twice a day for 14 days. The website www.c19early.com shows that these are the two approved drugs which individually have shown to be the most effective against Covid in two or more studies. Used together, these drugs have no common adverse interactions and have complementary mechanisms of action. For instance, fluvoxamine is a potent anti-inflammatory and, because it is able to penetrate the blood-brain barrier, it is effective in preventing inflammation in your brain. Unlike systemic steroids, fluvoxamine does not impair your ability to fight the virus so it can be used immediately. The fluvoxamine dose effective against Covid is just one third of the FDA-approved dose so side effects are very rare and minimal. I am not aware of anyone who started both drugs within 48 hours of first symptoms who didn’t have a rapid recovery. The best method to catch the virus early is to test regularly, and start treatment upon a positive test. This is because the PCR test can detect Covid before symptoms start.
4. The later you start treatment, the longer it may take you to recover and your outcomes will be more unpredictable. If you wait more than 48 hours beyond the onset of first symptoms, drug treatment will take longer to have a positive effect, higher doses and more drugs will be needed, and your outcomes will be more unpredictable. For example, when patients see their doctors more than 3 days after symptoms, a dose of 100mg twice a day of fluvoxamine is advised starting immediately. We highly recommend people talk to their physician about getting the drugs in advance, so that if they do get sick, they can start treatment immediately rather than waiting days or even a week for the medicine to arrive at the pharmacy.
5. Other drugs and supplements for outpatient treatment are effective for early treatment: There are many drugs and supplements that have varying levels of positive effectiveness against the virus including inhaled budesonide, bromhexine, vitamin D, and HCQ. All of these have the greatest value when started as early as possible. There is no benefit to waiting. In general, these drugs (and supplements) are safe with very low side-effect profiles. Your doctor may recommend adding one or more of these drugs at the start of treatment in addition to ivermectin and fluvoxamine. For patients with severe or worsening respiratory symptoms, 4-8 mg cyproheptadine 3-4 times a day has been shown to be very helpful as well.
6. Children are not exempt from these recommendations. Children are vulnerable too. Some doctors prefer to be “cautious” and refuse treatment to children unless they develop symptoms. I believe this is a huge mistake because outpatient treatment with repurposed drugs has been shown to be extremely safe. I know of children as young as 1.5 years old who have either developed permanent neurological problems from Covid or died because their doctor refused to treat them early. Doctors can prescribe pediatric dosing for affected children. All the doctors I know who have made the mistake of not treating early vow never to make it again.
7. Early treatment can prevent long-haul Covid. Nearly a third of people with Covid (even if asymptomatic) still suffer from lingering symptoms a median of 6 months after infection onset. These symptoms may be difficult or impossible to reverse in some people. The good news is that if you treat the virus fast and hard within 48 hours after first symptoms, you can avoid long haul Covid, hospitalization, and death. We haven’t heard of a single counter-example.
8. Higher dosing is required for more aggressive variants. There are many variants of the coronavirus. If you are getting treated early and your symptoms are not abating or not starting to noticeably resolve within 24 – 48 hours, you should talk to your doctor about increasing the dose of the drugs you are taking and/or adding additional drugs.
9. Not all drugs should be used early, especially systemic steroids. Using systemic oral steroids early on may impair your body’s ability to fight the off virus and is not recommended.
10. There are other drugs on the horizon, but they are not yet approved for use in most countries. Antivirals such as proxalutamide and interferon lambda have shown remarkable safety and efficacy in Phase 2 outpatient clinical trials. Expediting the Phase 3 testing and emergency-use approval of these two drugs in India could save countless lives.
11. If you are hospitalized, ask your doctor about treatment with cyproheptadine, inhaled adenosine and fluvoxamine. These three drugs have shown remarkable effectiveness in hospitalized patients and are very safe when given at the recommended dose. Case reports of patients given cyproheptadine have described lung function returning to normal in just 48 hours. Inhaled adenosine via a nebulizer has produced positive improvements in patient oxygen levels in as little as 10 minutes. Fluvoxamine has been shown to decrease the risk of death by 50% in an unpublished study of 58 patients in Croatia.
12. If you have long-haul Covid symptoms, four drugs may provide relief. The top four drugs used by Dr. Bruce Patterson who specializes in treating long-haulers are fluvoxamine, ivermectin, maraviroc, and simvastatin. Patterson’s lab has sophisticated software that analyzes blood test results and can quantify the amount of long-haul Covid and pinpoint which drugs should be used. The good news is that with these treatments, a high percentage of patients have been able to return to normal functioning. Long haul patients will notice that exercise uniformly exacerbates long-haul symptoms.
13. Drug quality matters. One of our doctors in India reported that fluvoxamine from all the major brands including Cipla, Torrent, Abbott, and Sun Pharma worked as expected, but drugs from less well-known brands were not as effective or ineffective. The same happened to one brand of ivermectin which was recalled in Brazil.
14. If fluvoxamine isn’t available, fluoxetine is a viable substitute. All the data we’ve seen shows that if you can’t get fluvoxamine, using 30mg once a day of fluoxetine (Prozac) is equally effective (equivalent to 50mg twice a day of fluvoxamine) (Scientific Reports 2021). However, Fluvoxamine is better than other SSRIs at activating a receptor known as sigma-1 that reduces the production of inflammatory signaling molecules called cytokines. Angela Reiersen, M.D., Ph.D., associate professor of psychiatry at Washington University in St. Louis, MO, and one of the new clinical trial authors, wrote on Twitter that researchers do not know whether fluoxetine (Prozac) can treat COVID-19. “It does not have as high affinity for the sigma-1 receptor, and no [randomized controlled trials] have been completed using fluoxetine for treatment of [COVID-19],” she wrote.

The recommendations above are based on both scientific studies and the experience of clinicians in treating Covid. For example, Dr. Amol Kothalkar, a cardiologist in Buldhana has been using these principles for the past 3 months on hundreds of patients in India and can attest to their effectiveness. They are also consistent with the superb Covid recommendations made recently by Dr. Vikas Sukhatme, Dean of the School of Medicine at Emory University.

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.

Fluvoxamine, Ivermectin and FLCCC I-MASK+ Protocol

Front Line COVID-19 Critical Care Alliance (FLCCC) Releases Updated Protocols for More Effective Treatment of COVID-19. Please refer to the latest FLCCC I-MASK+ protocol. Now updated to include additional drug treatments as well as a higher dose and frequency of ivermectin, the protocols become even more powerful weapons in the fight against the COVID-19 pandemic. Added to the protocols is the use of Fluvoxamine. Largely known as an antidepressant, Fluvoxamine has strong anti-inflammatory properties that have been shown in two trials to be highly effective against the inflammation caused by COVID-19.

Note about TOGETHER trial results for fluvoxamine and ivermectin

Why did Ivermectin seem to fail and Fluvoxamine not do so well? 

According to Steve Kirsch:

Ivermectin was dosed for 3 days; fluvoxamine for 10 days.

We don't think the trial was gamed at all. I think this was a legit result.

We know the Principal Investigator Edward Mills and believe he is totally honest and we have no reason not to believe the results he obtained. But we also believe other researchers as well.

So the question everyone has is how could these drugs do so well in other studies?

The answer: the variant was different. P1 is the variant in Brazil and makes Delta look like a walk in the park. If you do not treat P1, instantly upon symptoms, you will see big failures.

Had fluvoxamine been given on Day 0 instead of Day 4, there would have been a dramatically different result.

Had ivermectin been dosed at 0.6mg/day for 14 days starting on Day 0 (the first day of symptoms), there would have been a dramatically different result.

The more aggressive the variant, the earlier and harder you have to treat it.

Ivermectin likely failed for these four reasons:

• too little a dose
• started too late
• not continued for long enough
• many patients may have already been taking ivermectin

Those are the 3 biggest reasons. The healthcare systems need to encourage people to have the meds in the cabinet for immediate use. Nobody does that. That's why we have a problem.

Also, you can't treat Delta and P1 in the hospital... it is much much tougher there. It's like a fire department arriving when the entire building is in flames. 

Fluvoxamine vs Other Options

The recommendations below are based on both scientific studies and the experience of clinicians in treating COVID-19.

There are many drugs and supplements that have varying levels of positive effectiveness against the virus including inhaled budesonide, bromhexine, vitamin D and HCQ. All of these have the greatest value when started as early as possible. There is no benefit to waiting. In general, these drugs (and supplements) are safe with very low side-effect profiles. Your doctor may recommend adding one or more of these drugs at the start of treatment in addition to ivermectin and fluvoxamine. For patients with severe or worsening respiratory symptoms, 4-8 mg cyproheptadine 3-4 times a day has been shown to be very helpful as well.

The combination of ivermectin and fluvoxamine is extremely effective when used ASAP. Two of the most effective drugs to treat COVID early are ivermectin and fluvoxamine. Both drugs should be started together at the same time. If you are treated within 48 hours of first symptoms, research shows that ivermectin should be given at a dose of 0.4mg/kg for a minimum of 5 days or until symptoms resolve, whichever is later. Fluvoxamine should be given as 50 mg twice a day for 14 days. The website www.c19early.com shows that these are the two approved drugs which individually have shown to be the most effective against Covid in two or more studies. Used together, these drugs have no common adverse interactions and have complementary mechanisms of action. For instance, fluvoxamine is a potent anti-inflammatory and, because it is able to penetrate the blood-brain barrier, it is effective in preventing inflammation in your brain. Unlike systemic steroids, fluvoxamine does not impair your ability to fight the virus so it can be used immediately. The fluvoxamine dose effective against Covid is just one third of the FDA-approved dose so side effects are very rare and minimal. I am not aware of anyone who started both drugs within 48 hours of first symptoms who didn’t have a rapid recovery. The best method to catch the virus early is to test regularly, and start treatment upon a positive test. This is because the PCR test can detect COVID before symptoms start.

Find a Doctor who will Prescribe Fluvoxamine in US

MULTIPLE STATES (Telemedicine or online consultation)

CityHealth: https://www.cityhealthuc.com/fluvoxamine

CityHealth Locations:

13690 E 14th St., Suite 100, San Leandro, CA 94578
(510) 984-2489

1300 Clay St St., Suite 165, Oakland, CA 94612
(510) 984-2489

Related: 

• List of Doctors that will prescribe Ivermectin

• List of Pharmacies that will fill Ivermectin

References: 

• https://www.skirsch.io/how-to-treat-covid/
• Cheap, generic anti-depressant may reduce severe Covid-19 disease, study finds (CNN - Oct 2021)

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 CDC, WHO, and their local public health department as resources.