Reducing the Risk of Adverse Drug Events

Critics of mainstream medicine often point to the dangers of drugs. I previously wrote about “Death by Medicine,” where I explained the fallacy of fixating on harmful effects of drugs without putting them into perspective with all the good drugs do. Yes, patients have died from severe allergic reactions to penicillin, but penicillin has also saved countless lives.

A recent article in The New England Journal of Medicine looks at emergency hospitalizations for adverse drug events in elderly Americans. It confirms that adverse reactions are a serious problem, but some of its findings are surprising.

The elderly are seven times as likely as younger people to have adverse drug events. They are more susceptible because of physiologic changes with aging, frailty, coexisting conditions, and polypharmacy. Forty percent of people over 65 take 5-9 medications, and 18% take 10 or more. Combinations of medications can cause unexpected problems.

Among adults age 65 and older, they estimate nearly 100,000 emergency hospitalizations every year in the U.S. for adverse drug events.  Half of those were in those over age 80. And most of them were entirely preventable. If you tried to guess which drugs were most often to blame, you might guess NSAIDs or psychoactive drugs, but you would be wrong. Drugs previously recognized as “high-risk” in this age group were responsible for only 1.2% of these hospitalizations. Four medications were implicated in 67% of cases:

  • Warfarin 33.3%
  • Insulin 13.9%
  • Oral antiplatelet agents 13.3%
  • Oral hypoglycemic agents 10.7%

Further down the list are opioid analgesics, antibiotics, digoxin, and chemotherapy drugs. Even further down: sedatives, blood pressure meds, and anti-seizure medications. And nearly two thirds of hospitalizations were for unintentional overdoses. They concluded that simply improving management of commonly used antithrombotic and antidiabetic drugs could have a big impact, both in reducing harm and in reducing health care costs.

Warfarin, or Coumadin, is by far the biggest offender. Appropriate dosage varies with the individual and over time; adjusting it requires frequent blood tests to measure the INR (international normalized ratio of prothrombin time compared to a standard). It may be necessary to monitor the INR every day or two at first when readings tend to fluctuate markedly, and when the readings become stable the frequency of testing can drop down to monthly. Bleeding complications are more likely to occur when the INR goes above the target range. One specialist told me he had never seen a complication in a patient on Coumadin whose INR was in the target range.

It is conceivable that the biggest problem drug could entirely drop off the list and 33% of drug-related hospitalizations could be prevented if only doctors managed Coumadin dosing more effectively and if patients complied better with instructions about medication and diet. At my local hospital (Madigan Army Medical Center), all patients on anticoagulation are managed by a Coumadin Clinic run by an experienced clinical pharmacologist using rigorous procedures and guidelines; I don’t have any figures, but I think that approach is much better than having individual doctors manage their own patients.

A pharmacist, Robert Steven Gold, has written a book with specific proposals for reducing medication risks. The title is Are Your Meds Making You Sick? The title led me to expect a typical anti-establishment rant about evil Big Pharma poisons. It is anything but. The format is engaging: it presents a series of mini-mystery case reports and challenges the reader to detect which drug is the culprit.

Gold provides 16 rules for reducing the risk from drugs:

  1. Learn which medications are sending people to emergency rooms
  2. Know your kidney lab values
  3. Know your liver lab values
  4. Be aware that the elderly are different from younger people
  5. Take your meds as your doctor prescribed
  6. Know your lab-test schedule
  7. Know your medication’s monitoring parameters
  8. Don’t hesitate to call your doctor
  9. Be aware of drug interactions
  10. Understand that OTC meds, herbals, and alcohols are drugs too
  11. If your health changes after you add a new drug, think drug-induced disease
  12. Know that most adverse drug reactions are due to dosage issues
  13. Insist on medication reconciliation
  14. Don’t stop taking a medication without talking to your doctor
  15. Remember that elderly individuals should be on lower doses
  16. Ads don’t warn of incidence of adverse events – don’t believe them.

He explains each of these in detail, and refers to them as he goes through each mini-mystery. He adds “above all, record and report,” pointing out that the majority of drug reactions go unreported.

Just one mini-mystery example: a woman experiences weight loss, heartburn, nausea, weakness and dizziness. She is on medicines for high blood pressure and osteoporosis (Fosamax) and takes an over-the-counter non-steroidal anti-inflammatory drug (naproxen) for back pain. Endoscopy finds ulcers in her esophagus and stomach. Yes, we know NSAIDs cause GI bleeding, but in this case naproxen was only an accomplice. The real culprit was Fosamax, and the patient was to blame because she had failed to follow the instructions to take it with plain water and remain upright for 30 minutes after taking it. She had been taking it with orange juice and reclining in a chair for 30 minutes. She had also ignored the package insert for Fosamax that warns against combining it with NSAIDs. She had violated rules 5, 9, 10, and 16.

In 1860, Oliver Wendell Holmes famously said,

I firmly believe that if the whole materia medica could be sunk to the bottom of the sea, it would be all the better for mankind and all the worse for the fishes.

He wouldn’t say that today. We have come a long way since 1860. Modern science has developed effective medications that can save lives, control diseases, and relieve symptoms; but anything that has effects is likely to also have side effects, and these medications can also harm. Drugs can be hazardous to your health. Of course, not taking them can be even more hazardous: insulin reactions occur and can even sometimes kill patients, but if diabetics stopped taking insulin they would be certain to suffer unnecessarily and die prematurely. Both this article and this book are great examples of how science-based medicine is constantly striving to improve itself, in stark contrast to so-called “alternative” medicine: we recognize problems, confront them head-on, and try to reduce risks. Replacing medicine with “alternative” medicine because of drug reactions would be as foolish as replacing cars with walking barefoot because of automobile accidents.

Gold’s book contains essential information that anyone taking medications should know for their own safety, and that doctors should be more aware of. As a doctor, I already had a grasp of the basic principles, but reading this information taught me more about the details. Almost every mini-mystery case in Gold’s book could have been prevented by following his 16 rules. Both health professionals and consumers can do much better than we have been doing.


Posted in: Pharmaceuticals

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