Medication in the Time of COVID-19: Listen to the Experts

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COVID-19, the new disease that has put the world on edge, has spread around the globe with shocking rapidity. Guesses and half-baked hypotheses of how to treat it have spread almost as fast.

Pharmacologists and frontline doctors began exchanging messages weeks ago online: ibuprofen might be dangerous for people with COVID19. Then the medical journal Lancet Respiratory Medicine published a paper on March 11 hypothesizing that patients with diabetes and hypertension could be at greater risk of COVID-19 infection due to the medicines they take. Three days later, the French health minister tweeted that taking anti-inflammatory medications such as ibuprofen could worsen cases of the viral illness. And now, due to vague reports that certain antimalarial medicines might be effective against COVID-19, an Arizona man accidentally killed himself using antiparasite aquarium cleaner to treat the virus at home.

There are valid scientific reasons why ibuprofen, ACE2 inhibitors taken for hypertension, and antimalarials might all have effects on COVID-19 infections. But there are grave dangers in adjusting or self-prescribing medications without the advice of a doctor or pharmacist. We asked two UConn pharmacologists and a clinical pharmacist, an infectious disease specialist at UConn Health, and a Poison Control doctor for their best advice. Read it, educate yourself, and above all be safe: consult your doctor or pharmacist before adjusting your own medications. (And please—never, ever drink aquarium cleaner.)

Why all the noise about ibuprofen and COVID-19?
UConn professor of pharmacology and toxicology Xiaobo Zhong: Preliminary messages coming out of Europe indicate that ibuprofen (a common brand name is Advil) increases the rate of multiplication of the COVID19 virus. A study published in The Lancet indicates ibuprofen can increase the amount of ACE2 that cells make. ACE2 is a membrane surface protein that acts like a doorknob for COVID-19, allowing it to enter human cells and hijack them to make copies of itself.
We don’t know if other non-steroidal anti-inflammatory drugs such as aspirin also increase ACE2.

Is this really a big deal? How worried should I be about taking ibuprofen if I have a fever and think I might have COVID-19?
UConn department head and professor of toxicology José Manautou: Fever is a normal compensating mechanism in our bodies to help us fight infections. It’s not necessarily bad to have a fever. However, uncontrolled fevers with very high temperatures can lead to mental dysfunction, convulsions, and even coma.

We do not yet know how worried to be about ibuprofen. You can take acetaminophen (common brand names include Tylenol) instead. It’s good for fever and pain. But do not take higher than the recommended dose! If you take too much acetaminophen, you can damage your liver. Acetaminophen is the number one cause of acute liver failure in the US. If risk factors are present—if you’ve been drinking alcohol, or are malnourished from not eating because you are sick—toxicity can happen at doses lower than what is normally considered to be toxic, in some cases at doses within the therapeutic margin. If the recommended dose is not sufficient and you still have a fever, do not take more! Consult your pharmacist or physician.

What if I want more detailed information on treatment options?
Manautou: UConn pharmacy faculty have put together a detailed information sheet aimed at healthcare professionals.

Is there anything else I need to know about acetaminophen and COVID-19?
Zhong: Remdesivir, which is an antiviral drug just approved by the Food and Drug Administration to treat COVID-19, might cause liver inflammation in some patients. The evidence for this is from Ebola patients. It’s possible that combining acetaminophen with remdesivir could make patients even more sensitive to liver damage. We don’t have any indication that this will be an interaction, but it’s possible. Gilead, the company that makes remdesivir, has agreed to give us some of the drug to start a study on this.

What if I have diabetes or high blood pressure?
UConn Department Head of Pharmacy Practice Michael White: People with diabetes or high blood pressure are likely to be prescribed ACE inhibitors (lisinopril, enalapril, ramipril) and Angiotensin Receptor Blockers (ARBs; losartan, valsartan, candesartan). They’re the fourth and eleventh most used drug classes in the United States, with approximately 250 million prescriptions filled annually. Both ACE inhibitors and ARBs increase the amount of ACE2 in the body. The COVID-19 virus uses ACE2 to get into the body’s cells and multiply, so more ACE2 should mean more infection—theoretically.

But it’s not that simple. For patients with high blood pressure, chronic kidney disease, a past heart attack, or heart failure, suddenly stopping ACE inhibitors and ARBS can damage their hearts and kidneys and even hasten death.
And there’s a second reason not to stop taking the medicines. They might actually protect patients with COVID-19. ACE2 helps maintain the proper balance of sodium and potassium in the body. In people with heart disease and diabetes, that balance can be upset, and cause heart arrhythmias and kidney injury. In severe cases, COVID19 can cause similar problems to the body, and people with heart disease and diabetes are more at risk.

The bottom line is that while ACE2 is needed for the virus to enter cells, having a slight decrease in ACE2 because patients are no longer on ACE inhibitors or ARBs is unlikely to prevent infections.

How should I take care of myself or another member of my household with mild COVID-19?
UConn Health infectious disease specialist David Banach: The main focus is the management of their symptoms with supportive care (hydration, nutrition, etc.) while self-isolated from others within the home. The CDC has a nice patient education sheet addressing this. Frequent hand-washing, and cleaning any potential shared items/surfaces that others may come in contact with is also critical. If you have any new symptoms or worsening of your initial symptoms (fever, cough), you should call your healthcare provider to determine next steps. If symptoms are worsening over a relatively short period of time, this may warrant going to the emergency department. It’s essential that individuals with risk factors for severe disease, such as older age, or co-existent medical conditions, have a low threshold to seek care.

We recently learned of a death in another state due to someone trying using a toxic substance (aquarium cleaner) in an attempt to treat coronavirus. What can you tell us about that?
Dr. Suzanne Doyon, UConn Health assistant professor of emergency medicine: We’ve seen in the news that chloroquine is being studied for the management of coronavirus illness, but what we have seen from a poison control center perspective is people taking matters into their own hands and seeking chloroquine alternatives – for example chloroquine phosphate in aquarium products. The Banner Poison and Drug Information Center in Arizona reported that a person died this weekend after ingesting a chloroquine phosphate aquarium product. This person was using it as a substitute for pharmaceutical-grade chloroquine, and that is completely outside of what we would recommend.

What are the dangers associated with chloroquine?
Doyon: Chloroquine has been used for the management of malaria for decades. Both chloroquine and hydroxychloroquine have some usefulness in the management of certain inflammatory diseases such as rheumatoid arthritis and lupus. It must be emphasized that chloroquine is a very toxic medication, and when you ingest too much of it you will develop symptoms including loss of hearing, loss of vision, and potentially cardiac arrhythmias. Chloroquine is a prescription product and should always be taken under medical supervision.

Zhong: A previous study has shown chloroquine can exacerbate acetaminophen-induced liver injury in mice due to its ability to inhibit autophagy and mitochondria function. Whether hydroxylchloroquine can make liver damage worse in combinational use with acetaminophen is unknown. What are the up-limited doses of acetaminophen and hydroxylchloroquine for COVID-19 patients? Unknown. The knowledge is so urgently important for tens thousands of people who are suffering COVID-19 in the US and needs to be addressed quickly.

White: People should not start buying drugs like hydroxychloroquine over the internet from non-registered pharmacies (or ones that say they are from Canada) because they are likely counterfeit, and not only will they not help you, they could have harmful chemicals in them that could hurt you as well.

In August 2017, the National Association of Boards of Pharmacy (NABP) issued an update to their ongoing analysis of online pharmacies. NABP found that 95.8% of the 11,688 internet pharmacies they analyzed do not comply with US federal or state laws. Overall, 74.1% of the 108 internet sites stating they are from Canada are not sourcing drugs approved for use by Canadian citizens. Many of these drugs are counterfeits and have little or no active ingredients, some have other harmful drugs or chemicals in them, and others have heavy metal contamination.

What other potential remedies are worrisome?
Doyon: We’re hearing clinical trials are testing the combination of chloroquine and azithromycin (otherwise known as Zithromax or Z-Pak). The combination of the two has us particularly worried because of the high risk for heart rhythm disturbances, which may be very difficult to treat. Hopefully the combination of these drugs is administered by health care providers who are monitoring for these risks and are addressing these arrhythmias should they occur. But I can’t emphasize enough how risky the combination of the two medications could be in an unsupervised setting.

Has the Connecticut Poison Control Center been getting more calls about ingesting of hand sanitizer in recent weeks?
Doyon: The Connecticut Poison Control Center has found that hand sanitizer ingestions in children are about double what they were last year at the same time. That probably stems from the fact that there’s a lot more hand sanitizer in the household and environment. I want to stress that the ingredients in hand sanitizer can include ethanol, which is basically regular alcohol, or isopropanol, which is basically regular rubbing alcohol, both of which can cause a lot of problems in children. Especially alcohol, it can cause electrolyte abnormalities and serious toxicity in children. What we’d like people to understand is, when a child ingests this, it is best to call the poison control center, let us do a dose calculation and assessment, and make recommendations. A taste, lick, or drop can usually be safely managed at home. A teaspoon/tablespoon, depending on the size of the child, might mean a trip to the emergency department.

The Connecticut Poison Control Department at UConn Health is answering calls 24-7. Our nurses and pharmacists are well trained in all types of poisonings. About 75% of pediatric exposures are treated at home, saving parents visits to the emergency department and really helping limit that social interaction that occurs when one visits the hospital. When an ingestion or exposure has occurred, we urge parents, and all Connecticut residents, to call the poison control center first and foremost, so we can help determine what the best next step is.
NOTE: As of March 23, there have been no chloroquine-related calls to the Connecticut Poison Control Center since the COVID-19 outbreak.