In the United States most law-abiding citizens don’t run red lights. They know that the traffic rules are there to protect everyone from accidents. There’s also the fear factor. If a policeman catches you going through an intersection against the light, there is a hefty penalty. Some people ignore a different kind of red light. What do you do when the red check-engine light comes on in your car? Most people realize that this is a warning of a potentially serious problem. They pull over right away to investigate. Others, however, cross their fingers and hope they can reach their destination. Sometimes they get away with it. But sometimes continuing to drive can destroy the engine. When it comes to drugs, your physician or pharmacist might not catch dangerous drug interactions. These health professionals are super busy and not infrequently override the computer alerts, like ignoring the check-engine light.
A 50-Year-Old Warning About Dangerous Drug Interactions!
Fifty years ago, I wrote this for the book, The People’s Pharmacy (St. Martin’s Press):
“Drug interactions are the Achilles heel of the medical profession. The laws of nature no longer hold true. This is a crazy world where one plus one equals three, where down may very well be up and surely pigs have wings. In fact, mixing medicines is very much like playing Russian roulette. You never know when a particular combination will produce a lethal outcome.”
In those days, there were no computer programs to warn prescribers about dangerous drug combinations. These days prescribers and dispensers rely on digital systems to double-check for hazardous combinations. No thinking is required. But when humans rely upon computers to make life and death decisions, it can sometimes end badly.
A Broken System Fosters Dangerous Drug Interactions:
Physicians, nurse practitioners, physician associates and pharmacists are incredibly busy these days. We frequently hear from clinicians that they feel like they are on a conveyer belt rushing from one patient to another. They may not have much time to talk about drug side effects or warn about potentially serious interactions.
There is also the “cry wolf” phenomenon. Prescribers get so many computerized warnings that they tend to ignore many of them. There is even a name for this phenomenon: “alert fatigue.” Pharmacists too see digital alerts so often that they frequently override the software-generated drug interaction flags.
Do Doctors and Pharmacists Ignore “Red Light” Computer Warnings?
Physicians are often faced with the equivalent of a red light when they write an electronic prescription. The software that they use on the computer or a hand-held PDA has been programmed to alert them to dangerous drug interactions.
How the doctor, nurse practitioner or physician associate reacts to such alerts can make a life-or-death difference for patients. Too often, prescribers may override drug interaction notices.
A study conducted at six Veterans Affairs medical centers found that there were nearly 300,000 interaction overrides in one year (American Journal of Managed Care, Oct. 2007). Roughly three-fourths were for interactions considered “critical.” In such cases, doctors are supposed to justify the override but they failed to do so more than half the time.
Here is what these researchers discovered about dangerous drug interactions and the override problem:
“Despite the availability of a system to convey to all healthcare professionals useful clinical information about reasons to dispense 2 medications that interact, this study found that 53% of the time no reason was provided by a prescriber, despite the requirement to provide an override reason (for a critical DDI [drug-drug interaction] alert). This may represent a substantial flaw in the ability to use automated systems to prevent serious medical errors and to communicate the medical rationale for prescribing products in combinations that may cause harm to the patient.”
What is especially discouraging about the results of this study is the seemingly cavalier attitude of prescribers.
They did not provide a reason for overriding an alert 84% of the time:
“…despite the requirement to provide an override reason…Whatever the rationale, the fact that most of the time prescribers bypassed this opportunity to provide an override reason is problematic.”
Why Do Prescribers Ignore Dangerous Drug Interactions?
A study published in the Journal of the American Medical Informatics Association (March 2017) describes why they did the research:
“In this paper, we focus on alerts embedded in electronic prescribing systems (ePSs) and computerized provider order entry (CPOE) systems. These alerts are triggered at the point of prescribing and are designed to warn doctors about possible errors in orders, such as patient allergies, inappropriate dosing, or drug-drug interactions (DDIs). Alert fatigue, the mental state resulting from alert overload, is a frequent unintended consequence of clinical decision support implementation. Alert fatigue describes users becoming overwhelmed by and desensitized to alert presentation. A perceived consequence of alert fatigue is alert override: users move past the alert screen or box without canceling or changing an order in response to the information contained in the alert.”
The researchers conclude that alert override has become a habit with many prescribers. It would be as if you ran a red light once and got away with it…so you did it again. If you did not get caught and escaped an accident you might continue to run red lights.
After awhile this behavior might become a habit. The difference between red light runners and prescriber overriders is that they don’t risk an accident. The patient who gets a dangerous drug interaction is the one who suffers.
Pharmacists Also Suffer from Alert Fatigue:
Doctors are not the only ones who override interaction alerts. Pharmacy computers also flag potential drug incompatibilities. Dealing with dozens a day often leads to alert fatigue. A busy pharmacist may ignore or override such warnings and hope that nothing bad will happen.
Even when a pharmacist follows up on an interaction message by contacting the physician, the response is not always favorable. Many pharmacists have told us that their calls are sometimes ignored or dismissed. It may take a busy physician a day or more to return a call from a pharmacist. That leaves both the patient and the pharmacist hanging in limbo land.
Pharmacists are under incredible pressure these days. That’s why many have been going on strike…not for higher wages, but for less job pressure. We have heard from far too many pharmacists that working conditions are brutal, without time to go to the bathroom or take a break for lunch. When there is such pressure to fill as many prescriptions as possible in the shortest amount of time, mistakes can happen. Overriding interaction alerts can become tempting under such conditions.
Why Dangerous Drug Interactions Can Kill:
Interactions are responsible for many of the adverse reactions people suffer from medications each year. Michael Jackson, Anna Nicole Smith and Heath Ledger all died because of drug interactions. Incompatible drug combinations contribute to 20 to 30 percent of adverse reactions to medications.
We commonly hear from health professionals that they only override what seem like minor incompatibility reactions. But here is an example of a deadly interaction that could easily be ignored.
ACE Inhibitors + Co-trimoxazole Can be Deadly:
Lisinopril and losartan are blood pressure (BP) medications. They are among the most prescribed drugs in the country. About 34 million Americans take one of these drugs. Both preserve potassium in the body.
If one of these patients were to develop a urinary tract infection (UTI), it is entirely possible an antibiotic would be prescribed. About 5 million prescriptions are written annually for co-trimoxazole (sulfamethoxazole + trimethoprim, aka Bactrim, Septra), many for UTIs.
The drug interaction checker that we often use lists 75 medications that are “contraindicated” or should be avoided if someone is prescribed co-trimoxazole. They include both lisinopril and losartan because the combination can lead to life-threatening potassium buildup and fatal heart rhythms (BMJ, Oct. 30, 2014). The title of that article is:
“Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study”
I am going to let you in on a little-known secret about drug interaction software. It doesn’t always agree. The database described above lists the ACE inhibitor interaction of lisinopril with the co-trimoxazole antibiotic as “Avoid/Use Alternative.” In other words, do not prescribe or dispense this combination.
When I checked with one of the leading pharmacy chains in the US, there is a very different warning for this interaction. It describes the interaction as of “moderate” importance. Pharmacists are advised to “monitor for hyperkalemia (excess potassium).” That caution could easily be overridden or ignored. It would not protect a patient from “sudden death.” And if someone were to die because of excess potassium, it is unlikely the death would be attributed to a drug interaction.
We worry that if healthcare professionals override the warning against combining these familiar drugs, the outcome could be catastrophic.
Metformin + Topiramate & Lactic Acidosis:
The diabetes drug metformin is taken by more than 20 million Americans. It helps control blood sugar. But metformin can also interact with dozens of other drugs.
The FDA requires a black box warning for prescribers about a dangerous condition called lactic acidosis. The antiseizure medicine topiramate (Topamax) increases the risk for this potentially deadly problem.
Simvastatin + Amlodipine & Rhabdomyolysis:
Two of the most commonly prescribed drugs in the pharmacy are simvastatin to lower LDL cholesterol and amlodipine to control hypertension. Roughly 8 million people take simvastatin daily in the US and 18 million people take amlodipine. Do prescribers know about the possibility of dangerous drug interactions with such drugs?
Some statins, such as lovastatin or simvastatin, can interact with the commonly prescribed blood pressure medicine amlodipine. This combination could increase the risk for life-threatening muscle breakdown (rhabdomyolysis) and kidney failure.
Because of such dangerous drug interactions, prescribers are supposed to limit the statin dose to 20 mg for patients taking amlodipine, amiodarone or ranolazine. If someone were taking verapamil, diltiazem or dronedarone, the FDA requires this caution:
“Do not exceed simvastatin tablets 10 mg once daily.”
There are a bunch more medications that are extremely hazardous with simvastatin. People on this medication require super vigilance to avoid dangerous drug interactions! By the way, atorvastatin also has the potential to interact dangerously with a number of medications including certain antiviral medications, antibiotics and antifungals.
Antidepressants + Triptan Migraine Meds & Serotonin Syndrome:
Patients who take an antidepressant such as sertraline (Zoloft) or fluoxetine (Prozac) should be warned not to take a triptan-type migraine medicine such as eletriptan (Relpax), rizatriptan (Maxalt) or sumatriptan (Imitrex).
The FDA has warned prescribers that such a combination could result in serotonin syndrome. Symptoms include uncontrollable twitches or muscle contractions, shivering and tremor, sweating, agitation and confusion. People can go into coma or die as a consequence of serotonin syndrome.
Final Words:
Do you begin to comprehend the gravity of the drug interaction problem? You can see that this is an enormous potential problem. When busy prescribers see an interaction alert on their screen, what do they do? Some reconsider the prescription. But as mentioned at the top of this article, many ignore the warnings because of alert fatigue.
Pharmacists are supposed to detect incompatible combinations of medications. They represent a safety net for prescribers. But they too may override interaction warnings on their computers.
Even when a pharmacist decides that an interaction needs further investigation before dispensing, she may run into a roadblock at the doctor’s office. Sometimes the physician fails to return a pharmacist’s call, or even several calls. This leaves the pharmacist and the patient in a quandary.
You would never mix ammonia and bleach together. That combination creates dangerous chloramine gas. You do not want to mix dangerous drug combos in your body! To assist patients in their quest for drug information, we have prepared a free Drug Safety Questionnaire for the pharmacist and physician to fill out.
Perhaps it’s time for prescribers and dispensers to stop overriding drug alerts. Just as drivers should not ignore yellow or red lights, physicians and pharmacists need to exercise caution when faced with potentially dangerous drug interactions.
Please share your thoughts in the comment section below. Have you ever experienced an incompatibility reaction? Would you even know if you had? We welcome your thoughts on this topic.
