You vs. “ALERT FATIGUE” – Preventing Dangerous or Fatal Drug Interactions!

You’re heard the story of the boy who cried wolf, right? It’s about a shepherd boy who keeps warning his village that a wolf is attacking the sheep just because he got lonely. After a few too many of these false alarms, the villagers stop believing him. When a real wolf shows up, nobody comes to rescue the hapless sheep. The same thing happens with medicines. Sadly, physicians and pharmacists have far too often been lulled into complacency when it comes to drug combinations. They get so many warnings about problematic or even fatal drug interactions that they may experience something called “alert fatigue.” It can lead to disasters for patients. That is why it is crucial for you to do your own drug interaction checking!

You Know About Fatal Combinations!

Most people have heard about the danger of combining certain household cleaners. Putting ammonia and bleach together can generate chloramine gas. If someone creates this toxic brew and inhales the gas, symptoms may include coughing, trouble breathing, irritation and pain in the nose, throat and lungs, wheezing, burning eyes and pneumonia. Without medical attention, this interaction could lead to coma and death.

Bleach (sodium hypochlorite) should not be added to acidic chemicals like vinegar. Some people think that they can add bleach to toilet bowl cleaners for added disinfection. BAD idea! Toxic gas could be the outcome. And do not add bleach to rubbing alcohol (isopropyl alcohol). This combination can create chloroform and hydrochloric acid. Bleach should not be combined with hydrogen peroxide, oven cleaners, drain cleaners or window cleaners.

Beware Fatal Drug Interactions:

I really care about drug interactions! This topic is personal for me. My mother died at one of the country’s premier hospitals after angioplasty to open one coronary artery that was only about 35% occluded. That night, a resident administered IV Demerol, even though I had repeatedly told the medical staff that she could not tolerate opioid narcotics like Demerol (meperidine).

The Demerol interacted with another medicine she was taking to cause serotonin syndrome. That combination created uncontrollable muscle contractions, the last thing a patient needs after having a catheter removed from an artery in the groin area. It led to uncontrollable internal bleeding and ultimately her death.

I have no idea if anyone checked for drug interactions or just ignored a possible warning. Whatever the cause, it has reinforced my fears about dangerous or fatal drug interactions.

Electronic Medical Records Should Prevent Dangerous or Fatal Drug Interactions!

When your doctor writes a prescription, she is supposed to know everything else you are taking and check that the new medication won’t interact. Long ago, doctors and pharmacists had to look the combination up in a big book like the PDR (Physicians Desk Reference) or some other print resource. It could take a long time. Today, interaction warnings are computerized and available almost instantly.

In theory, that should make checking for incompatibilities much easier. But it is still far from seamless. Many physicians and pharmacists complain about “alert fatigue.”

Why Alert Fatigue Can Overwhelm Prescribers and Dispensers!

We heard a while ago from a healthcare provider.

She gets frustrated with excessive alerts the computer presents:

“The number of alerts is mind-boggling. If a patient is allergic to anything, I get an alert for every medication I prescribe. And I have to go through a rigmarole to get to the reason for the alert to see if it is relevant or not. I don’t need to know about a wool allergy.

“Drug-drug interactions are more serious, but the alerts look identical to non-relevant alerts. For years, I have been asking the software provider to improve this, to no avail.

“I tell patients about common OTC interactions, like don’t take a cold medication with DM on the label. The cough suppressant dextromethorphan (DM) interacts badly with antidepressants like SSRIs or SNRIs.

“If someone has migraines, I warn them about common migraine meds even if they aren’t taking them at the time of the appointment. 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. They 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 scrip for the new medication about this during the appointment. Or, if you forget, ask the pharmacist when you pick up the new medication. Don’t ask the provider 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 use. I will ask repeatedly about these because this stuff is important! Prescribers need to know what is going into your body. Please compile a list with dosage and type (extended release, etc.) so we can add it to the software. I promise I won’t judge you for taking St. John’s wort. I just need to know.

“I myself bring such a list to every appointment with my providers. You can also take a picture of your medications. I take photos of my medication bottles all lined up and send it to my husband. I also send him an updated list of medical diagnoses. If there were an emergency where I can’t speak for myself, he would have it right there on his phone.

“My brother-in-law took a picture of his 89-year-old mother’s medications when he visited her last summer. That sure came in handy when I had to take her to the emergency room while we were traveling! She only had her pills in a pill organizer, so there were no labels to identify them.”

Are Doctors, Nurse Practitioners, PAs, and Pharmacists Checking for Dangerous or Fatal Drug Interactions?

We have all become dependent upon computers and assume they rarely, if ever, make a mistake. Hardly anyone relies on an actual map to figure out how to get from point A to point B. Admit it now, when was the last time you actually held a paper map in your hands or planned a trip? Almost everyone relies on a satellite-based computerized directional system. Such programs are great…if they work.

What Do You Know About Lisinopril Interactions?

Here is an example of a computerized drug interaction that leaves, in my opinion, room for error. If a person were to take the #1 most prescribed blood pressure drug in America, lisinopril, we would hope that both the prescriber and the pharmacist would warn about potentially fatal drug interactions. First, the patient should be told to avoid low-salt substitutes that contain potassium chloride!

Next, the patient should be warned that if they ever have to take an antibiotic, it should not contain the drug trimethoprim! This ingredient is found in brands such as Bactrim or Septra and the generic formulation designated sulfamethoxazole/trimethoprim (SMZ/TMP). It is also called co-trimoxazole. That’s pretty confusing, but critical information. This antibiotic is frequently prescribed for urinary tract infections, ear infections, respiratory tract infections and even traveler’s diarrhea.

You can easily imagine how a patient taking lisinopril for hypertension might also develop an ear infection or a urinary tract infection for which a different health care professional might prescribe co-trimoxazole. Some computer systems warn prescribers or pharmacists to:

“Monitor potassium levels: This combination may increase the risk for hyperkalemia.”

Hyperkalemia means too much potassium in the body. The trouble is that by the time someone actually orders a blood test for potassium, it could be too late. Hyperkalemia can come on fast and it can kill without warning (BMJ, Oct. 30, 2014). You can read an actual story about just such a fatal drug interaction at this link.

Do Prescribers Recognize Dangerous Drug Interactions?

When prescribers were tested about their knowledge of drug interactions, they performed miserably (Drug Safety, June 2008). They were given 14 drug pairs to classify as forbidden, risky or not a problem. They got the right answer on fewer than half the pairs. Any high school student who scored below 50 percent on a test would fail.

The authors of this research concluded:

“This study suggests that prescribers’ knowledge of potential clinically significant DDIs [drug-drug interactions] is generally poor. These findings are supported by other research and emphasize the need to develop systems that alert prescribers about potential interactions that are clinically relevant. Physicians most commonly reported learning about potential DDIs from pharmacists, suggesting further work is needed to improve the drug-prescribing process to identify potential safety issues earlier in the medication use process.”

These days, most prescribers don’t even try to remember dangerous drug combinations. They rely heavily on their computers or smart phones to do the heavy lifting. But because of alert fatigue, they may override many interaction warnings. A study found that even when physicians had access to a wireless handheld device with interaction information, they were just as likely to prescribe a bad combination (Journal of Managed Care Pharmacy, Jan-Feb., 2012).

The authors concluded:

“A stand-alone medication management program in a wireless PDA [personal digital assistant] device was not frequently used by most prescribers to update patient medication histories and was not associated with a reduction in the rate of prescribing potentially clinically important DDIs [drug-drug interactions].

One Last Crucial Factoid:

Here is a secret that no one likes to talk about. Neither drug companies nor the FDA knows everything there is to know about interaction problems at the time of a new medicine is approval for sale (Journal of Clinical Pharmacology, March, 2025).

Sometimes a dangerous or fatal interaction is only discovered after a pharmaceutical has been on the market for years. Not all pharmaceutical manufacturers are as conscientious about searching for drug-drug interactions after a new medicine is approved by the FDA.

Final Words:

Whether the drug in question is lisinopril for hypertension, simvastatin for high cholesterol, sertraline for depression or warfarin to prevent blood clots, patients and their families need to be alert for possible dangerous combinations. Don’t assume the prescriber is aware of all the drugs a patient is taking or the hazards of mixing medicines. Our book, Top Screwups Doctors Make and How to Avoid Them (online at www.peoplespharmacy.com) has tips for preventing fatal drug interactions!

Pharmacists may catch hazardous combinations before they are dispensed, but like prescribers, they may also override computerized alerts. Even when they detect serious problems, it can be challenging for them to communicate directly with the prescriber and arrange for a less dangerous medication.

Anyone who takes more than one pill at a time should always trust, but verify. Ronald Reagan’s favorite slogan applies to medicine as much as to international politics. Because doctors, physician associates, nurse practitioners and pharmacists are so busy these days, they could easily miss an important interaction. That’s why we always encourage patients to be their own advocates. Drug interaction checkers can be found at Drugs.com, DrugBank.com and Medscape.com.

If you think this article is important, please share it with friends or family members. We bet some of these people are taking lisinopril, sertraline or simvastatin! Why not suggest that your acquaintances subscribe to our free newsletter at this link? Thank you for supporting our work.