Over a million people are harmed every year by adverse reactions to prescription drugs. Interactions between incompatible medications cause many of these. Others are caused by just too damn many medicines. Older people are especially vulnerable to deadly drug interactions. That’s because they take the most medicines. During the COVID pandemic, drug-drug interactions have also led to avoidable deaths. Why aren’t computer programs preventing deadly drug interactions?
Identifying Drug Interactions in Patients With COVID-19:
Physicians treating patients for COVID-19 should be extra vigilant for drug-drug interactions. That’s the conclusion of a study from Italy (JAMA Network Open, April 19, 2022). The researchers reviewed studies involving nearly 1,300 patients.
There were a total of 575 drug-drug interactions (DDIs). In other words, doctors were prescribing a lot of incompatible drug combinations to patients with COVID-19. Over 300 of these DDI led to at least one adverse drug reaction.
A Paxlovid Success Story!
We love it when we hear about conscientious health professionals who ask all the right questions and work hard at preventing deadly drug interactions. Here is just such an example:
Q. My wife and I, both in our 60s, took Paxlovid when we caught COVID on vacation in New Mexico last fall. She tested positive first, and the doctor who helped us over the phone asked all the right questions about medication. He told her to discontinue her rosuvastatin while taking Paxlovid to avoid complications.
He also asked about her GFR [glomerular filtration rate], a measure of how effectively kidneys filter the blood. We were able to look up her recent test results and give him her 90ish number.
Because one of the components of Paxlovid inhibits the kidneys from filtering out some substances — in order to keep the other antiviral agent working in the bloodstream — there are two dosage levels of Paxlovid offered. One is for people like my wife whose kidneys are efficient. The other has half the dose of antiviral for people like me whose kidneys don’t work so well. Doctors need to ask about kidney function as well as drug interactions when prescribing Paxlovid.
A. Thank you for this important reminder. Paxlovid reduces the risk of serious complications from COVID-19. That said, physicians and pharmacists must check very carefully for dangerous drug interactions. Kidney function should also be assessed, as you so thoughtfully explained.
Unfortunately, not all health professionals are as conscientious as this doctor. Anyone prescribed Paxlovid needs to verify that there are not any incompatible medications that could interact.
Preventing Deadly Drug Interactions with Hydroxychloroquine:
Remember the controversial drug hydroxychloroquine (HCQ)? At the beginning of the pandemic, some doctors (and politicians) promoted it as a highly effective treatment for the coronavirus. The FDA even issued an emergency use authorization (EUA) for HCQ.
Pharmacies ran out and patients who needed the drug to treat their lupus or rheumatoid arthritis symptoms had a hard time accessing this medication. It wasn’t effective to prevent or treat COVID-19, though. As a result, the FDA eventually revoked the EUA.
While hydroxychloroquine was being prescribed in large numbers, drug interactions with HCQ were surprisingly common. They led to a dangerous heart rhythm change called long QT interval. You can learn about this deadly arrhythmia at this link.
Are You at Risk of Sudden Death from Hydroxychloroquine?
The authors of the drug interaction review (JAMA Network Open, April 19, 2022) noted:
“Most DDIs resulted in QT-interval prolongation. Such a dangerous alteration was found 20 times, and in 12 of these 20 cases, it occurred together with other adverse outcomes, even leading to the death of 8 patients.”
Preventing Deadly Drug Interactions!
Computers are supposed to help prevent deadly drug interactions! The doctors and pharmacists who prescribe and dispense these drugs are supposed to watch for incompatible combinations of medicines. Even if they could not keep dangerous DDIs in their heads, they all have access to smart phones, tablets and computers that can access this information in seconds.
The authors of the new study note that organizations such as Medscape, Drugs.com, COVID-19 Drug Interactions, WebMD and LexiComp offer alerts about the very interactions identified in this analysis. 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 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 new 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. Yet 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.”
Share your own experience with medications in the comment section below.
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