Drug Injury Watch

Medication Mistakes And Pharmacy Errors Continue To Be A Large Problem

Prescription Drugs Wrongly Prescribed Or Improperly Dispensed Are Preventable Adverse Events Which Need To Be Reduced In Number -- And This Can Be Done

(Posted by Tom Lamb at DrugInjuryWatch.com)

In a February 14, 2008 article, "1 in 10 patients gets drug error", Boston Globe reporter Patricia Wen presented some disturbing data from a study which examined adverse events involving prescription errors that occurred in six undisclosed Massachusetts community hospitals:

One in every 10 patients admitted to six Massachusetts community hospitals suffered serious and avoidable medication mistakes, according to a report being released today by two nonprofit groups that are urging all hospitals in the state to install a computerized prescription ordering system.

The report is the first large-scale study of preventable prescription errors in community hospitals, and its author, Dr. David Bates of Brigham and Women's Hospital in Boston, said he was surprised that these mistakes were so frequent in these community hospitals....

The researchers reviewed a total of 4,200 randomly selected patient medical charts at the six community hospitals, covering stays from January 2005 to August 2006. An average of 10.4 percent of patients suffered a preventable "adverse drug event" - defined as a case in which the patient was given a drug even though the medical records noted that the medication could trigger a drug allergy or that the dose given would exacerbate a medical condition. Medication errors were counted only when patients suffered serious reactions, including going into shock or suffering kidney failure. In nearly every instance, the patients remained in the hospital longer to recover from the mistake. Nobody died from any of the mistakes, researchers said.

This February 14 article in the Globe goes on to describe how the computerized prescription ordering system mentioned above works, as well as what types of results its use can produce:

[T]e computerized physician order entry system, which requires doctors to type into a central database every medical order, including prescriptions, diagnostic tests, and blood work. The doctors' orders are matched against the patient's medical history, triggering red flags to prevent problems related to drug allergies, overdoses, and dangerous interactions with other drugs.

Bates said that after this system was put in place at Brigham and Women's Hospital in 1995, preventable medication errors declined by 55 percent over the next two years....

Ms. Wen includes in her article various discussions about how medical insurers, government officials, and healthcare providers, all, would benefit from the computerized system being used at more hospitals in Massachusetts and across the nation.

Turning to another aspect of medication errors, on February 12, 2008 the Indianapolis Star published a lengthy USA Today article, "Too many prescriptions, too few pharmacies", which reported the results of an investigation that USA Today conducted:

The investigation reviewed policies and alleged errors at rivals Walgreens and CVS, the nation's two largest drugstore chains, which fill nearly one-third of all retail prescriptions nationwide. It included a review of scores of lawsuits, as well as pharmacy board disciplinary actions in 10 states and interviews with pharmacists, drug-error victims, their families and attorneys. Some common factors emerged:

• Too many prescriptions, too few pharmacists....
• An emphasis on speed....
• A reliance on technicians....
• Pharmacist incentive awards....
• Counseling gaps....

We learned from this February 2008 USA Today article about prescriptions being improperly filled by pharmacists that, remarkably, the North Carolina Board of Pharmacy is the only state board that requires all major drug errors to be reported to the agency.

The online version of this USA Today article has an interactive graphic component, "How prescriptions are filled and where errors can occur", which gives one a better idea about what goes on behind the counter at your typical chain-store pharmacy.

For anyone interested in the causes and effects of medication errors, both of these February 2008 news reports are well worth your time.

Millions In U.S. Fail To Take Their Medicine Correctly, And The Consequences Can Be Deadly

Medication Non-Adherence In America Is A National Crisis Costing Billions Of Dollars According To An August 2007 Report

(Posted by Tom Lamb at DrugInjuryWatch.com)

Two July 30, 2007 articles by Lauran Neergaard, a reporter who covers health and medical issues for The Associated Press (AP), bring us some important information about prescription medication adherence, or the lack thereof, in the U.S.

The first AP article by Ms. Neergaard, titled "Report: Skipping Doses Could Be Deadly" by The Washington Post, presents these findings from a report to be issued in the first part of August 2007 by the nonprofit National Council on Patient Information and Education:

• Particularly at risk are people whose diseases are initially symptom-free. Although high blood pressure more than triples the risk of heart disease, for example, just 51 percent of patients stick with their prescribed antidote.
• Also at high risk are the elderly, but adherence is a problem for all ages. As few as 30 percent of teenagers correctly take drugs to prevent asthma attacks, for example.
• Poor medication adherence can cost an extra $2,000 a year for each patient in extra doctor visits alone, and it's associated with as many as 40 percent of nursing home admissions, even more costly.
• Add preventable hospitalizations and premature death, and the report estimates that poor medication adherence could be costing the country $177 billion in medical bills and lost productivity.

The second AP article by Ms. Neergaard, titled "Tips to Help Patients Take Meds Properly" by The Baltimore Sun, provides patients with some advice items intended to help them better understand and adhere to their medication prescriptions:

• Before leaving the doctor's office with a new prescription, ask detailed questions including: How and when do I take this? When do I quit? What food, drink, other medicines or activities should I avoid while using this medicine? What is it supposed to do? How do I know if it's working? What are its possible side effects? What do I do if have those?
• Bring to each doctor's appointment a complete list of all prescription and nonprescription medicines you take, so the doctor can check if a planned new drug will interact badly with an existing one. If you use one pharmacy exclusively, the pharmacist can print out a prescription list for you.
• If you have problems understanding the instructions that come with the medicine, ask the pharmacist for help. There may be a simpler brochure, large-print instructions, or translations into languages than English.
• Patients who forget doses could try setting up pill boxes at the beginning of each week with morning, noon and night doses in separate compartments. Technology including "talking" pill boxes that sound an alarm when doses are missed also are under development.

We encourage you to help spread the word about this National Council on Patient Information and Education August 2007 report regarding our significant medication non-adherence problem here in America.

As part of an earlier four-part series on adverse drug reactions, called "ADRs in US", I wrote an article that looked at another aspect of the medication non-adherence problem, namely how the failure of some doctors to provide essential prescription drug information to their patients contributes to this growing problem.

Coincidentally, that particular "ADRs in US" series article is featured -- together with posts from 76 other bloggers -- in the new eBook BlawgWorld 2007 (available as a free download in PDF format), which was released on July 30, 2007.

The Adverse Drug Reactions And Medication Errors That Require Hospital Care Most Often

Some Lessons Learned From A "Top 10" Drug Errors Session At The American Pharmacists Association 2007 Annual Meeting

(Posted by Tom Lamb at DrugInjuryWatch.com)

The American Pharmacists Association (APhA) Annual Meeting was held in Atlanta, Georgia earlier this year.  A large number of the 7000 attendees took time out of their busy schedules for one of the meeting's most popular sessions, "The Top 10 Adverse Drug Reactions and Medication Errors", which was presented by Matthew Grissinger, RPh, FASCP, a medication safety analyst with the Institute for Safe Medication Practices (ISMP).

As reported in a Medscape.com article by Kathryn L. Hahn, PharmD:

Grissinger first referred to a study that identified the 10 drugs most commonly implicated in adverse events requiring treatment in a hospital emergency department (ED). The study also documented the frequency with which each of the 10 drugs was involved:

1. Insulin (8%);
2. Anticoagulants (6.2%);
3. Amoxicillin (s) (4.3%);
4. Aspirin (2.5%);
5. Trimethoprim-sulfamethoxazole (2.2%);
6. Hydrocodone/acetaminophen (2.2%);
7. Ibuprofen (2.1%);
8. Acetaminophen (1.8%);
9. Cephalexin (1.6%); and
10. Penicillin (1.3%).

According to this May 2007 Medscape.com article, Dr. Grissinger said approximately 40% of these adverse drug events that required a patient to be treated at a hospital emergency room involved unintentional overdoses. 

More generally, so-called "nonadherence issues" were the usual cause for adverse drug events that led to a trip to the hospital; among them were:

• taking incorrect doses;
• taking doses at the wrong times;
• forgetting to take doses; and,
• stopping the medication too soon.

Dr. Grissinger's presentation at the APhA 2007 Annual Meeting also covered the top 10 medications most frequently involved in drug errors.  By definition, drug errors are unintentional acts committed by healthcare providers involving medications.

As many have heard by now, in 1999 the Institute of Medicine (IOM) published a report, "To Err Is Human: Building a Safer Health System", which included their finding that as many as 7000 Americans die from medication errors each year.

From the 2007 Medscape.com article, this is what was learned about medication errors at the Grissinger session:

A somewhat different top 10 list identifies medications that are most commonly misused or mishandled in some way by healthcare professionals. This list is based on information from the United States Pharmacopoeia (USP), which maintains a database of medication errors that are reported anonymously. The figures represent drug errors associated with acute hospital care[5]:

1. Insulin (4% of all medication errors in 2005);
2. Morphine (2.3%);
3. Potassium chloride (2.2%);
4. Albuterol (1.8%);
5. Heparin (1.7%);
6. Vancomycin (1.6%);
7. Cefazolin (1.6%);
8. Acetaminophen (1.6%);
9. Warfarin (1.4%); and
10. Furosemide (1.4%).

Patients who have experienced an adverse drug reaction or a medication error requiring hospital treatment can submit a confidential report to the USP-ISMP Medication Errors Reporting Program (MERP), a voluntary program which is operated by the U.S. Pharmacopeia (USP) in cooperation with the Institute for Safe Medication Practices (ISMP).

More Than One Million Hospitalized Patients Experienced Adverse Drug Reactions (ADRs) In 2004

Findings Of April 2007 AHRQ Report On Side Effects And Other Medication Problems In American Hospitals

(Posted by Tom Lamb at DrugInjuryWatch.com)

A recent online article provided a summary of the findings from the "Adverse Drug Events in U.S. Hospitals, 2004" report issued in April 2007 by the Agency for Healthcare Research and Quality (AHRQ).

According to this online article, entitled "Over 1 Million American Hospital Patients Experience Side Effects And Other Problems With Their Medications":

• In 2004, 1.2 million hospitalized patients experienced an adverse drug reaction (ADR);
• 90 percent of these ADRs were due to a side effect from a medication that was properly administered; and,
• Just 8.6 percent of ADRs among hospitalized patients were because they were given the wrong drug or the wrong dose in the hospital or because they accidentally took an overdose or the wrong drug before entering the hospital.

Other findings from this April 2007 AHRQ report, which is part of its Healthcare Cost and Utilization Project (HCUP), and published in its Statistical Brief #29:

• Average total hospital costs for patients who experienced drug side effects or other ADRs were $2500 more than for patients who did not experience any drug side effects or other ADRs  ($10,100 compared with $7,600);
• Corticosteroids, blood thinners, and anti-cancer drugs were the top three types of drugs involved in these hospital ADRs, and those events which involved drug side effects were mostly due to side effects from properly administered medications;
• As for those hospitalized patients who suffered side effects from properly administered drugs, they tended to be older (average age: 64 years old) than patients who suffered from side effects related to wrongly administered medication (average age: 47 years old); and,
• Nearly 60 percent of the hospitalized patients in America who experienced an ADR during 2004 were women.

Healthcare providers and patients who are interested in these findings about ADRs in American hospitals may also want to take a look at the "List of High-Alert Medications", which is put out by the Institute for Safe Medication Practices (ISMP).

According to this ISMP document:

High-alert medications are drugs that bear a heightened risk of causing significant patient harm when they are used in error.  Although mistakes may or may not be more common with these drugs, the consequences of an error with these medications are clearly more devastating to patients.

Lastly, healthcare providers and patients are encouraged to report actual as well as potential medication errors to the Medication Errors Reporting Program (MERP).  Such reports can be made online at http://www.ismp.org or by calling 1-800-FAIL-SAFE.

List Of Internet Sites That Provide Medication Information And Drug Interaction Checkers

Patients Should Use These Free Self-help Resources In Addition To Telling Doctor About All Current Drugs And Supplements

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the February 27, 2007 edition of the Washington Post staff writer January W. Payne compiled a list of free internet sites which patients can use to research newly prescribed drugs and to check for possible dangerous drug interactions.

There are actually two lists of internet medical sites in this Post article, the first is "Medication Information" and the second is "Drug Interaction Checkers".

Of course, as pointed out in the prelude to these two lists, a patient should let their doctors and pharmacist know about every prescription drug as well as any and all dietary supplements -- vitamins, minerals, herbs -- they are currently using when there is any talk about a new medication being added to their drug therapy regimen.

To be clear, the internet resources compiled in this February 27 Post article are meant to supplement, not replace, the patient's discussion with their doctors and pharmacist.

In an era where patients seem to be prescribed more and more drugs by their several different doctors, self-help as regards potentially fatal drug interactions is vital.

Health Canada's MedEffect Now Offers Online Reporting Of Adverse Drug Reactions

Objective Is To Increase Percentage Of ADRs That Get Reported To Regulators

In October 2006 Health Canada announced that its MedEffect web site is now able to accept online reports of suspected adverse drug reactions (ADRs) for those prescription medications marketed in Canada.  This announcement was published in the Canadian Adverse Reaction Newsletter, Volume 16, Issue 4, released in October 2006.

Before this electronic upgrade and practical improvement, doctors or patients who wanted to report serious side effects due to use of a prescription drug had to call in, fax, or mail a paper ADR report form to Health Canada.

According to Health Canada, the new MedEffect online reporting system generates a file that can be printed and stored electronically by the person submitting an ADR report online. As with the earlier methods of reporting ADRs to Health Canada, any and all information regarding the identity of a subject patient as well as the person making the ADR report to the MedEffect program will be kept strictly confidential.

According to Health Canada's October 2006 Canadian Adverse Reaction Newsletter:

Underreporting of [adverse drug reactions] is a well-known global issue. International studies have estimated that only 1%-10% of all [ADRs] are reported. Health professionals have identified barriers to reporting that relate to the inconvenience and lack of user-friendliness of reporting.

A link to Health Canada's MedEffect web site can be found in the sidebar, under the heading Resources.

(Posted by: Tom Lamb)

Some Common But Severe Drug Interactions Involving Coumadin (Warfarin)

Beware Of "G" Herbs and Supplements: Garlic, Ginseng, Ginkgo Biloba, and Ginger

In April 2006 Douglas S. Paauw, M.D., a University of Washington medical investigator, spoke at an American College of Physicians meeting about adverse events associated with Coumadin (warfarin) therapy which are caused by drug interactions.

As explained in an April 9, 2006 MedPage Today article by Peggy Peck:

Adverse events associated with Coumadin therapy continue to be a leading cause of hospitalizations for drug-related adverse events, and many times the problem can be traced to those herbs and supplements, he said. Dr. Paauw ran through those and other hazards during a session titled, "Ten Common Prescribing Errors: Drug Interactions and Side Effects."

Starting with the herbs and supplements, Dr. Paauw had an easy-to-remember bit of advice: be particularly careful with herbs and supplements beginning with the letter "G".  Garlic, ginger, and gingko biloba, all increase the anticoagulation of Coumadin (warfarin).  Meanwhile, ginseng decreases the anticoagulation of Coumadin (warfarin).

According to the April 9, 2006 MedPage Today article, Dr. Paauw told the audience of doctors that "the most severe Coumadin adverse events are often traced to Bactrim aka Septra (TMP/sulfa), a frequently prescribed antibiotic in elderly patients who are also the most likely users of Coumadin."

During his presentation, Dr. Paauw listed several other prescription drugs that are likely to interact with Coumadin, including these:

• erythromycin,
• amiodarone,
• Diflucan (fluconazole),
• Nizoral (keotoconazole),
• Sporanox (itraconazole), and
• mentronidazole.

Dr. Paauw also mentioned that the use of Prilosec (omeprazole) or Tylenol (acetaminophen) while using Coumadin at the same time can affect a patient's INR.

As pointed out in the MedPage Today article, Dr. Paauw's presentation emphasized these two lessons concerning drug safety:

1. Patients need to know that herbs, supplements, and vitamins can react with prescription drugs: and,
2. Patients should, on a regular basis, tell their doctor(s) about all prescription and non-prescription drugs that they are using in order to reduce the risk of adverse events caused by drug interactions.

(Posted by: Tom Lamb)

Zocor-Amiodarone Drug Interaction Causes Rhabdomyolysis; Fifth Such Case Reported

Causation Theory: Zocor Is Metabolized By Same Enzyme Which Is Being Inhibited By Amiodarone

On March 14, 2006 The Annals of Pharmacotherapy published online an article about what the authors described as "the fifth reported instance, as of February 15, 2006, of a severe interaction between simvastatin and amiodarone."  Simvastatin in sold by Merck under the trade name Zocor.  Amiodarone is sold by Wyeth as Cordarone, and by Upsher-Smith as Pacerone; several companies sell a generic version of amiodarone, also.

This latest case report involves a 72-year-old white man who started taking amiodarone (200 mg/day) on July 10, 2004, and on August 13 started taking Zocor (80 mg/day) while continuing the amiodarone. The patient was hospitalized on September 21, 2004 after complaining of thigh weakness and achiness; he also reported having dark urine for 7 days.

At the time of his hospital admission, the patient's relevant lab results were as follows:

• creatine kinase (CK) 19,620 U/L (reference range 60-224);
• blood urea nitrogen 50 mg/dL;
• creatinine 2.6 mg/dL;
• aspartate aminotransferase (AST) 912 U/L (30-60);
• alanine aminotransferase (ALT) 748 U/L (30-60);
• urine myoglobin 71,100 µg/L (<50); and,
• serum myoglobin 13,877 µg/L (<110).

Upon admission, the Zocor and amiodarone were discontinued.  The patient was ultimately diagnosed with rhabdomyolysis, renal failure, and possibly hepatotoxicity.  After appropriate treatment, the patient recovered over the course of the next couple of weeks.

The authors of this drug-drug interaction case report in The Annals of Pharmacotherapy arrived at these conclusions:

1. "An objective causal assessment suggests that rhabdomyolysis, renal failure, and possibly hepatotoxicity were probably related to an amiodarone-simvastatin [i.e., Zocor] interaction."
2. "[Zocor] is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This may, therefore, account for the presumed drug interaction."

The authors pointed out that this patient had pre-existing diabetes mellitus, hyperlipidemia, and hypertension, as well as mild azotemia.  They did not, however, believe that these pre-existing medical conditions were substantial contributing causes as concerned the drug-induced rhabdomyolysis.

(Posted by: Tom Lamb)

"Black-box" Warnings Are Forgotten Or Ignored By Some Doctors

The So-called Black Box Is FDA's Highest Form Of Drug Safety Alert

In the February 14, 2006 edition of the medical journal Archives of Internal Medicine there is a report that many patients are told by their doctors to use prescription drugs with "black-box" warnings in situations contrary to the drug-safety information and guidance set forth in those warnings.

Black-box warnings are the highest form of drug safety alert and, because of their importance, usually appear at the top of a drug's package insert, or label.  Typically the black-box warning brings attention to serious side effects associated with the drug, and provides guidance about how to minimize the risks of those side effects -- such as to not prescribe a particular drug with another drug, or to patients with certain pre-existing medical conditions.

In this study report published by the Archives of Internal Medicine, researchers examined the health records of 324,548 outpatients seen at several Boston-area medical clinics from January 1, 2002 to December 31, 2002.  The researchers found that 33,778 patients were prescribed a medication that had a black-box warning; of those, 2,354 prescriptions were contrary to the guidance set forth in the subject black-box warning.

In about 1,000 cases, the patients were simultaneously taking one or more drugs that the black-box warning said should be avoided so as to prevent a possible drug-drug interaction.  It is presumed that in most of those situations the black-box warning was forgotten by the prescribing doctor.

Interestingly, most of the instances which involved a black-box drug, about 90%, also involved prescribing the black-box drug to treat a disease or medical condition for which use of that drug was not even approved by the FDA. This type of prescribing is commonly referred to as "off-label" use.  In some of those cases, just as the doctor decided to use his or her own discretion as opposed to relying on the FDA-approved use, it is presumed that the prescribing doctor may have purposely chosen to ignore a black-box warning.

While this study found that the number of patients who received a black-box drug in a situation contrary to the substance of the black-box warning is relatively small, i.e., compared with the total number of outpatient prescriptions examined for the study, according to the researchers "the absolute number of outpatients at risk is substantial."

As always, we urge patients to know about the serious side effects, and the symptoms thereof, which are associated with any prescription drug they are taking.  To that end, we provide this listing of side effects and drug interactions for reference.

(Posted by: Tom Lamb)

The Chance of Having an Adverse Drug Reaction Event Increases With Patient Age

Drug-drug Interactions are a Leading Cause of Drug Reactions, and Growing Due to Polypharmacy

Because older adults often take more medications than younger adults, the number of adverse drug reactions increases with patient age. Adverse drug reactions, however, frequently go unnoticed or are misdiagnosed in older people for the following reasons:

• Drug reactions sometimes mimic signs or symptoms of disease (e.g., dementia).
• Symptoms of a drug reaction are thought to be caused by an existing medical condition or the onset of a new health problem.
• Physical reactions to medication, such as fatigue, falling, or weight loss, may be mistakenly labeled as "normal" aging.

There are many physical signs that may be attributed to an adverse drug reaction. These include:

• fatigue
• constipation or diarrhea
• confusion
• incontinence
• frequent falls
• depression
• weakness or tremors
• excess drowsiness or dizziness
• agitation or anxiety
• decreased sexual behavior

If a problem develops shortly after a person begins taking a new prescription drug, it is advisable to contact the prescribing doctor, or some other doctor, immediately.  Beware that sometimes it takes more time for an adverse reaction to occur, making it less obvious to the patient that their medical "problem" might be an adverse reaction associated with one or more of their drugs.

One sub-set of adverse drug reactions that is growing in number is drug-drug interactions.  Simply put, a drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug in the body. For example:

• One drug might reduce or increase the effects of another drug.
• Two drugs taken together may produce a new and dangerous interaction.
• Two similar drugs taken together may produce an effect that is greater than would be expected from taking just one drug.

Polypharmacy -- which is generally defined as the use of at least three prescription drugs at the same time -- is on the rise in the U.S. for a variety of reasons, among them direct-to-consumer advertising and the mind-set that every ailment has a remedy in the form of a pill.  When a person is taking several concomitant drugs, there is a higher risk of suffering an adverse drug reaction.

Some examples of how prescription drugs can interact with each other follow:

• Mixing antidiabetic medication (e.g., oral hypoglycemics) and beta blockers (e.g., Inderal) can result the decreased response of the antidiabetic drug and increased frequency and severity of low blood sugar episodes.
• Mixing antidiarrheal medication (e.g., Lomotil) and tranquilizers (e.g., Transxene, Valium), sedatives (e.g., Dalmane, Quaalude), or sleeping pills (e.g., Amytal, Nembutal, Seconal) can result in an increased effect of tranquilizers, sedatives, or sleeping pills.
• Mixing antihypertensive medication (e.g., Reserpine, Aldoril, Combipres) and digitalis (e.g., Lanoxin) can result in abnormal heart rhythms.
• Mixing anticoagulants (e.g., Coumadin, Warfarin) and sleeping pills (e.g., Nembutal, Amytal, Seconal) can result in decreased effectiveness of the anticoagulant medication.

In addition to prescription drugs interacting with each other, over-the-counter drugs can also interact with prescription drugs. Some examples of this type of drug interaction include:

• Aspirin can significantly increase the effect of blood thinning drugs (anticoagulants), thus increasing the risk of excessive bleeding.
• Antacids can cause blood-thinning drugs (anticoagulants) to be absorbed too slowly.
  Antacids can interfere with drug absorption of antibiotics (i.e., tetracycline), thereby reducing the effectiveness of the drug in fighting infection.
• Antihistamines, often used for allergies and colds, can increase the sedative effects of barbiturates, tranquilizers, and some prescription pain relievers.
• Decongestants in cold and cough medications can interact with diuretics or "water" pills to aggravate high blood pressure.
• Iron supplements taken with antibiotics can reduce or stop the ability of the antibiotics to fight infection. (The chemicals in the supplement and the antibiotic bind together in the stomach, instead of being absorbed into the bloodstream.)
• Salt substitutes can interact with "water" pills or blood pressure medication to increase blood potassium levels. This can result in symptoms of nausea, vomiting, muscle cramp diarrhea, muscle weakness, and cardiac arrest.

These are just a few of the many interactions that can occur when multiple drugs are taken together.  Accordingly, it is very important that a patient check with their prescribing doctor(s) and dispensing pharmacist(s) to make sure that the combination of drugs prescribed to them does not have the potential to interact so as to cause them to suffer an adverse drug reaction.

(Posted by: Tom Lamb)