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Preventing Deadly Drug Interactions Harder Than You Think

Do you swallow 3+ pills daily? Preventing deadly drug interactions is hard, but essential! Prescribers and pharmacists bemoan alert fatigue.

If I told you that over 2 million people were harmed while flying on an airplane and 100,000 people died each year in airplane crashes you would be astounded. You might be reluctant to get on an airplane given such grim statistics. That of course does not happen! But the FDA states that as many as 2,216,000 serious adverse drug reactions may occur each year in hospitalized patients leading to up to 106,000 deaths. That does not take into account medication-related harms or deaths in the outpatient setting. Many of these tragedies are related to dangerous combinations of medications (Drugs & Aging, Feb. 2023). Why aren’t computer programs preventing deadly drug interactions?

A Health Care Provider Explains Why Preventing Deadly Drug Interactions is Hard: Alert Fatigue!

A few weeks ago, we wrote a column about dangerous drug combinations. We chastised prescribers for overriding computer alerts that warn about potentially problematic drug-drug interactions (DDIs). Then we heard from a health care professional with an explanation about “alert fatigue.”

“In my practice I prescribe psychiatric drugs. The number of computer alerts we receive is mind-boggling. If a patient is allergic to anything, I get an alert for every medication I prescribe. So if the patient is allergic to wool, I get alerts. Allergic to latex? Peppermint? ALERT ALERT ALERT!

“I have to go through a rigmarole to find the reason for the alert to see if it is relevant or not. Meanwhile, I’m trying to give the patient my full attention and not take too long to respect the next patient’s time.

“Consequently, I only add medication allergies to patients’ charts to minimize this onslaught of alerts. I do put in any serious allergy that resulted in anaphylaxis.

“Drug-drug interactions are a different matter, but the alerts look identical. I have been begging the software provider for years to change this without any improvements. All my colleagues who use software for prescribing complain about this too.

“I tell patients about common OTC interactions. For example, don’t take a cold medication with DM (dextromethorphan) if you’re on an SSRI or SNRI antidepressant. I also upload information about serotonin syndrome to their portal account to make sure they have that information.

“Patients need to be more active in their care. Patients often message me between appointments to ask about interactions with a new medication they started with another provider. Please ask the provider who wrote the script for the new medication during the appointment. Or, if you forget, ask the pharmacist when you pick up the new medication. Don’t ask me, whom you haven’t seen for months.

“Patients often fail to tell me what OTC medications, vitamins, supplements, herbals, birth control, inhalers, creams, eye drops or recreational drugs like nicotine or alcohol they are using. This information is important!

“I wish everyone would compile a list of everything they take so we can add it to the software. I won’t judge you for taking St. John’s Wort. I just need to know. If a provider is judgmental about it, get a new provider.

“I take such a list to every appointment with my own providers. You can also take a picture of your medications. My brother-in-law took a picture of his 89-year-old mother’s medications when he visited her last summer. That came in handy when I had to take her to the emergency room when we were traveling!”

What Can Happen When Drug Interactions Are Overlooked or Ignored?

This reader describes a situation in which a doctor was not committed to preventing deadly drug interactions:

“I learned the hard way about drug interactions. I almost died from serotonin syndrome.

“My doctor was slow to diagnose this reaction. I avoid SSRI antidepressants now. I had two seizures because of drug interactions. My neurologist told me trazodone and bupropion caused a grand mal seizure. Now I have to take anti-seizure meds.”

Preventing Deadly Drug Interactions!

Computers are supposed to help prescribers and pharmacists prevent deadly drug interactions! Health professionals who prescribe and dispense medications are supposed to watch for incompatible combinations of medicines. Even if they cannot keep dangerous DDIs (drug-drug interactions) in their heads, they all have access to smart phones, tablets and computers that can access this sort of information in seconds.

The authors of a study about DDIs in COVID patients note that organizations such as Medscape, Drugs.com, COVID-19 Drug Interactions, WebMD and LexiComp provide alerts for health professionals (JAMA Network Open, April 19, 2022).

Using such tools should be very helpful in preventing deadly drug interactions.

What Went Wrong?

We do not have a good explanation for why many health professions have not been preventing deadly drug interactions.

The authors point out that:

“The current study was planned to analyze DDI-associated clinical outcomes that occurred in clinical practice during the pandemic and to investigate whether and how drug interaction checkers might be useful to assess them. Our main finding is that the use of these tools could have identified several DDI-associated ADRs [adverse drug reactions], including severe and life-threatening events.

“Of importance, all the drug interaction checkers used in our study could have identified such events.

“Drug interaction checkers identified potential DDIs that involved nirmatrelvir-ritonavir [Paxlovid] and several drugs, such as colchicine, statins, antithrombotic, immunosuppressant, and antineoplastic agents, and DDIs that involved fluvoxamine combined with antidepressants, antiplatelet agents, benzodiazepines, and fentanyl.”

The Conclusions:

The authors conclude:

“The findings of this systematic review of drug interactions among patients with COVID-19 reported in databases and the literature suggest that extreme caution should be used in choosing COVID-19 therapy, especially in polytreated patients. Although a critical emergency, such as the COVID-19 pandemic, might justify an urgent clinical approach, possible DDIs should never be ignored when choosing the most effective and safest therapy.”

We could not agree more! And we would extend the caution to all drugs, not just those prescribed for COVID-19. Health care providers must use drug-drug interaction checkers and pay attention to alerts! Otherwise, people will be harmed and some will die. Anyone taking the COVID-19 drug Paxlovid must be especially vigilant for DDIs!

Too Many Meds?

Dr. Emily Reeve is a clinical pharmacist in Australia. She has pointed out that when senior citizens take inappropriate medicines, they run a serious risk of harm. In addition, the health care system wastes billions of dollars. Dr. Reeve estimates that the average older Australian takes six medicines daily. One of those six is either unnecessary or contraindicated.

The Cochrane Database of Systematic Reviews (June 10, 2020) published an analysis of blood pressure pills in older people.

Dr. Reeve and her colleagues note that medications prescribed for hypertension have both benefits and risks:

“Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug-drug interactions and can contribute to increasing medication-related burden.”

They wondered whether there were studies on the effect of deprescribing some of the BP drugs. Sadly, the evidence was surprisingly crappy. However, none of the studies that had been done showed that cutting back on some blood pressure medications increased the risk of heart attacks or led to more deaths.

Deprescribing Is Hard to Do:

Drug companies have not done studies on safe ways to take people off medicines they don’t need. Let’s face it, they have no incentive to help people stop taking medications. In addition, doctors may be reluctant to do so without guidance.

The FDA has not been helpful in this respect, either. We are especially concerned about the lack of guidance in helping patients stop taking benzodiazepine-type anti-anxiety meds, antidepressants and powerful acid-suppressing drugs (PPIs). The more medicines a person takes, the greater the risk of deadly drug interactions.

Preventing Deadly Drug Interactions:

Unfortunately, physicians are not always aware of the potential hazards of drug interactions. One study found that prescribers did poorly on a take-home test of which drug combinations should not be taken together (Drug Safety, June, 2008). Only one in five, for example, was aware that the anti-anxiety drug alprazolam (Xanax) is incompatible with the anti-fungal agent itraconazole (Sporanox).

It is not surprising that prescribers have a hard time remembering dangerous drug interactions. There are, after all, way too many hazardous combinations to memorize them all.

Why Can’t Computers Prevent Deadly Drug Interactions?

Experts had hoped that electronic prescribing with a computer or smart phone would alert doctors to possible problems before they write a prescription. There is growing recognition, however, that technology alone is inadequate to protect patients from harm (Journal of Managed Care Pharmacy, Jan-Feb, 2012).

Doctors frequently ignore and override the drug interaction alerts that pop up on their computer systems (American Journal of Managed Care, Oct., 2007). Insiders refer to this as “alert fatigue” because physicians become desensitized to interaction warnings. Pharmacists can also be overwhelmed by computer alerts that they believe are not that worrisome. But overriding an alert could lead to disaster.

A study of discharge prescriptions reveals the seriousness of the problem and also a potential solution (Annals of Emergency Medicine, Feb. 2013). Researchers reviewed 674 prescriptions (roughly half) of all those written over a three-week period at a busy emergency department.

Nearly one fourth of the children’s prescriptions and eight percent of the adults’ medications had significant errors and posed a risk to patients. That was even after a review by electronic drug checkers. In this investigation, pharmacists discovered the mistakes and checked with the prescribers, who admitted their errors and changed the medication.

Because children are so vulnerable to medication mistakes and drug interactions, Children’s Medical Center in Dallas has put 10 full-time pharmacists in the emergency department to review each prescription before it is dispensed. They review 20,000 prescriptions every week and prevent a significant number of interactions and other prescribing problems.

Patients Must Help in Preventing Deadly Drug Interactions!

This is expensive, so very few hospitals use this effective strategy to double-check prescriptions. That’s why patients themselves need to be extra vigilant.

A reader related this experience:

“I had a very bad interaction from taking Gralise, tramadol and Cymbalta. They told me that I had serotonin syndrome.”

The pain reliever tramadol (Ultram) and the antidepressant duloxetine (Cymbalta) both work on the neurochemical serotonin and together they can cause serotonin syndrome. Symptoms of this life-threatening reaction include agitation, fever, sweating, uncontrollable muscle contractions, rapid heart rate and hallucinations. It can progress to coma and death. Gabapentin (Gralise) also interacts with both tramadol and Cymbalta, so the entire combination was risky.

Preventing Deadly Drug Interactions:

Ron shared this close call:

“I was taking Bactrim for a urinary infection last year. I also take losartan on a daily basis for hypertension. My physician did not catch this potentially dangerous drug interaction.

“Many years ago a leader in my trade group said: ‘you are the guardian of your own welfare.’ That quotation had nothing to do with medicine but in so many ways it is true. Doctors really can screw up badly, even now with a laptop full of your medical info right in front of them. I can see I will have to be more diligent in the future.”

What, you might ask, is the problem with combining the BP medicine losartan with the antibiotic Bactrim (co-trimoxazole or TMP-SMZ)? When a person combines an ARB-type blood pressure medicine or an ACE inhibitor such as lisinopril with this antibiotic, their potassium levels can rise too high. That can lead to cardiac arrest (BMJ, Oct. 30, 2014).

A pharmacist we know saved a man’s life by telling him to stop taking his potassium supplement after TMP-SMZ was added to his losartan BP pill. That combination could easily have led to death.

You can learn more about how to protect yourself from such scary interactions through our book, Top Screwups Doctors Make and How to Avoid Them. You may think this can only happen to someone else. But if you are taking drugs such as Advil, Aleve, aspirin, warfarin, lisinopril, valsartan or ramipril, to name just a few, you need to be proactive in preventing deadly drug interactions.

Here is a link to our book with its chapter on incompatible combinations and our “Top 11 Tips for Preventing Dangerous Drug Interactions.”

To help you and those you love avoid drug interactions we have prepared a Drug Safety Questionnaire and Medical History form. This free downloadable PDF will allow your prescriber and pharmacist to note any worrisome drug interactions. If can be found under the Health eGuides tab.

Share your own experience with medications in the comment section below.

A Small Favor:

We remain one of the few independent voices for you, the patient. Prescription drug commercials fill a huge amount of TV air time. If you are sick and tired of all the misinformation, we would like to ask a small favor. Google has made it virtually impossible for people to find our articles on the web.That’s hardly surprising given all the prescription drug ads you will see there.

If you find our work worthwhile, please send this article to friends and family via email, Twitter or Facebook. There are icons at the top of the page to make it easy. Tell them to download the free Drug Safety Questionnaire and Medical History form. That way they can get their prescriber and pharmacist to fill it out independently. They can check for agreements and disagreements between these health professionals. This tool should help in preventing deadly drug interactions.

You can also encourage your contacts to consider subscribing to our FREE electronic newsletter. Subscribers get expanded versions of our syndicated newspaper columns and free access to our public radio show via our weekly podcast. Here is a link to help people subscribe. Thank you so much  for supporting our work. You might also want to send a copy of our book, to your relatives who are taking a handful of medications each day. Here’s the link. You could be helpful in preventing deadly drug interactions!

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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  • Conti V et al, "Identification of drug interaction adverse events in patients with COVID-19: A systematic review." JAMA Network Open, April 19, 2022. doi:10.1001/jamanetworkopen.2022.7970
  • Reeve, E., et al, "Withdrawal of Antihypertensive Drugs in Older People," Cochrane Database of Systematic Reviews, June 10, 2020, doi: 10.1002/14651858.CD012572.pub2
  • Hughes, J.E., et al, "Prevalence of Drug-Drug Interactions in Older Community-Dwelling Individuals: A Systematic Review and Meta-analysis," Drugs & Aging, Feb. 2023, doi: 10.1007/s40266-022-01001-5
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