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According to a new study by the Agricultural Health Study, a government funded program established in 1993 to examine the negative effects of pesticides on farming families in Iowa and North Carolina, regular exposure to the pesticide diazinon may cause lung and other types of cancer.

Diazinon (an organophosphate) is a pesticide that is derived from nerve gases that were introduced during World War II. In 2004 the chemical was removed from use in garden and lawn products because of evidence the substance could cause neurological disorders and other health problems that were not cancerous.

The findings of the recent study suggest a link between diazinon and lung cancer. Data showed that in 2002, 301 of 4,961 men who were exposed to the chemical in the workplace had developed lung cancer while only 968 of 18,145 of  the subjects without daily exposure to the chemical got cancer.

In the report published in the American Journal of Epidemiology, Dr. Michael C. R. Alavanja from the National Cancer Institute in Rockville, Maryland, and his colleagues stated: "We found evidence of an association of lung cancer and leukemia risk with increasing lifetime exposure days to diazinon."

The results corroborate a previous report by Agricultural Health Study which covered a less extensive period of time. The findings were also not impacted when cigarette smoking was accounted for, indicating that cigarettes do not explain the increased risk of lung cancer.

Although in a 1997 review of diazinon, the EPA classified the chemical as "not likely a human carcinogen" based on studies in rodents, the results from Agricultural Health Study confirms other laboratory and epidemiologic data that suggests the pesticide does pose a risk.

In response the EPA has offered to institute new restrictions on diazinon’s use. According to the 2004 data, about 4 million pounds of the chemical was applied agriculturally in America.

Most people are familiar with the fact that acetaminophen is a popular over-the-counter (OTC) pain reliever. What is generally not known by consumers, however, is just how widely used acetaminophen is or how dangerous it can be when misused.

Although acetaminophen is most commonly associated with Tylenol, it is also an active ingredient in hundreds of OTC (Excedrin, Midol Teen Formula, Theraflu, Alka-Seltzer Plus Cold Medicine, and NyQuil Cold and Flu) and prescription (Vicodin and Percocet) drugs. Thus, research has found that 36% of Americans take acetaminophen in some form at least once every month.

As a result of its widespread market disbursement, acetaminophen has gradually become associated with the group of medications (including aspirin, cough and throat lozenges, and antacids) that are no longer respected as being potentially dangerous. This casual treatment of any drug, especially acetaminophen, has had grave consequences indeed.

More than 10 years of medical research has found that in sufficient amounts, acetaminophen is toxic to the human liver. Thus, overdosing (intentional or unintentional) with the drug can cause acute liver failure. The public, however, has not seemed to have gotten the message.

Despite all of this information concerning the dangers associated with the drug generally and with overdosing specifically, the number of unintentional acetaminophen poisoning cases has continued to increase with dire results.         

According to the authors of a new study published in the December issue of Hepatology, which is the official journal of the American Association for the Study of Liver Diseases (AASLD): “Acetaminophen poisoning has become the most common cause of acute liver failure in the United States.”  Although many of those cases involve attempted suicides, almost 50% are the result of unintentional overdoses.

The problem with unintentional overdoses is that, unlike intentional overdoses, they are usually not recognized until significant liver damage has already occurred. Intentional overdoses can, and usually are, treated with N-acetylcysteine; unintentional overdoses rarely are.

The researchers conducted a prospective study of patients presenting with acute liver disease to 22 academic centers participating in the Acute Liver Failure Study Group. Of 662 consecutive patients between 1998 and 2003, 275 had acetaminophen-related acute liver failure.

Acute liver failure cases attributable to acetaminophen poisoning increased from 28% in 1998 to 51% in 2003. These patients were mostly female (74%) and Caucasian (88%). Suicide attempts accounted for 44% of the cases while 48% had overdosed unintentionally. This occurred by either by taking combinations of products containing acetaminophen or taking more than the recommended dosage of a single product over time.

Of all patients studied with acetaminophen-related acute liver failure, 74 died, 23 received liver transplants, and 178 survived without transplantation.
     
Prescription acetaminophen compounds accounted for 63% of the accidental overdoses and 38% of the subjects had been using two acetaminophen medications simultaneously. According to the researchers: "This suggests patients lack awareness of the hazards of over-the-counter acetaminophen use in combination with prescribed agents."  

A significant finding was that some patients reported taking less than 4 grams of acetaminophen per day before falling ill, thus: "Our data suggests that there is a narrow therapeutic margin and that consistent use of as little as 7.5 g/day may be hazardous." The data also suggest that there is no chronic form of acetaminophen injury, rather, a safety threshold that, when exceeded, has catastrophic results.

Dr. Tim Davern, a gastroenterologist with the liver transplant program of the University of California at San Francisco and one of the authors, observed: "I see some young women who have been suffering flulike symptoms for the better part of a week, and not eating much. They start with Tylenol, and maybe add an over-the-counter flu medicine on top of that, and pretty soon they’ve been taking maybe six grams of acetaminophen a day for a number of days. In rare cases that can be enough to throw them into liver failure."

Each Extra Strength Tylenol tablet contains half a gram, or 500 milligrams, of acetaminophen, and arthritis-strength versions of the pain reliever contain 650 milligrams. One tablet of Midol Teen formula contains 500 milligrams of acetaminophen, as does one adult dose of NyQuil Cold and Flu. One dose of Tylenol Cold and Flu Severe contains 1,000 milligrams. The recommended maximum daily dose for adults is 4 grams, or 4,000 milligrams.

The diverse nature of the compounds containing acetaminophen and the difficulty consumers have in interpreting label information usually prevents consumers from keeping track of the cumulative amount of the drug they are taking on a daily basis. Because of this, many experts have urged the FDA to require large warnings to be placed on any product containing acetaminophen.

In proper doses, acetaminophen remains a very safe drug. The problem is that the safe dosage level can be easily exceeded by consumers who either take a little extra of one product to get the pain relief they need or take a number of remedies containing the drug without monitoring the cumulative dose of acetaminophen the products contain.

Another problem is that many narcotic/opiate (Vicodin, Percocet) or alcohol-based (NyQuil) compounds are often abused or taken in increasingly larger doses to achieve relief or because of addiction. As a result, the acetaminophen content is ignored and reaches dangerously high levels. 

Experts agree that most people can safely take the four-gram daily maximum that labels recommend for adults - the equivalent of eight Extra Strength Tylenol spread across 24 hours many even take much more without harm.
When eight grams in a single day is reached, however, a significant number of people whose livers have been stressed by anything from a virus or alcohol to other medications run the risk of developing serious problems. When a single dose reaches 12 to 15 grams, without immediate medical intervention, the death rate is about 50%.

While the researchers noted the incidence of acetaminophen overdose is still low compared to the millions of tablets consumed on a daily basis, their findings were considered startling enough to propose changes in the way acetaminophen is sold.

"Efforts to limit over-the-counter package size and to restrict the prescription of narcotic-acetaminophen combinations (or to separate the narcotic from the acetaminophen) may be necessary to reduce the incidence of this increasingly recognized but preventable cause of acute liver failure in the United States."

When it comes to acetaminophen, the simple warning issued by the makers of Tylenol says it all: “Anything more than the recommended dose is an overdose.”

As the number of prescription and over-the-counter drugs has steadily increased, so have the medical problems associated with dangerous side-effects and interactions.

One very serious problem caused by the sheer number of drugs, however, is the existence of similar sounding names for drugs that are intended to treat vastly different conditions. These mix-ups can be deadly as a recent case in Massachusetts illustrates.

In September, we reported on the death of an elderly man who entered Brockton Hospital in Boston with bipolar disorder. He was lucid and had no life-threatening illnesses. Unfortunately, four days later he was dead; killed by a massive dose of the wrong medication.

The patient was given 60 times the recommended dose of Librium when he was supposed to have received Lithium.

Even after a nurse discovered the initial mistake, the hospital continued to give the man other antidepressants and sedatives. He also received two doses of antibiotics over six hours late.

The hospital attempted to engage in damage control by claiming telling The Patriot Ledger that autopsy results showed the man had died of pneumonia.

According to a hospital spokesman: "When the error was found the doctor and the patient’s family were immediately notified. Brockton Hospital immediately launched an investigation and has taken several steps to ensure that this will not happen again."

The errors started when a pharmacist ordered Librium, a sedative taken for anxiety, for the patient instead of Lithium, which he was the drug actually prescribed for his bipolar disorder.

Amazingly, the pharmacist told investigators that even though he realized his mistake immediately, after failing to reach a nurse by telephone, he “forgot to follow through” on the matter. There was plenty of time in which to correct the mistake since the medication was not administered until the next morning.

While the two drugs have similar sounding names, the safe dosage for each is vastly different. A safe dose of Lithium runs up to 600 milligrams a day. The recommended dose of Librium for elderly people, however, is but 5 milligrams two to four times daily.

Thus, the patient received 300 milligrams of Librium, a full 60 times the safe dose of a drug he wasn’t even supposed to receive.
    
Another potentially serious mix-up that warrants another review exists between three drugs with similar names but vastly different effects have led to serious health problems. The drugs are:

• TOPROL-XL® (metoprolol succinate) – AstraZeneca – a beta blocker used to treat high blood pressure, heart failure, and angina used to treat hypertension, chest pain and some kinds of heart failure.
• TOPAMAX® (topiramate) – Ortho-McNeil Neurologics Inc. –  used to treat epilepsy and to prevent migraines.
•  TEGRETOL® (carbamazepine) – Novartis – used to treat some kinds of seizures and trigeminal neuralgia (a nerve disorder that causes stabbing head pain). 
  

The FDA and AstraZeneca, have advised doctors that patients who received the wrong drugs reported recurrences of seizures, hallucinations, and hypertension. At least one suicide attempt was possibly linked to failing to receive the right drug, and at least one patient who erroneously received Toprol-XL experienced a dangerous drop in heart rate.

In addition, a priority educational marketing campaign was launched by Ortho-McNeil Neuologics, Inc., to warn healthcare professionals about the possibility of confusion between its product TOPROL-XL® extended-release tablets and TOPAMAX® tablets.

The FDA and other health authorities have received a number of reports from patients receiving one of the drugs instead of the other. These mix-ups have occurred when prescriptions were written incorrectly, read incorrectly, or labeled incorrectly.

Although taking the wrong medication for a specific health problem is always problematic and may pose serious health consequences, this particular situation is extremely dangerous given the severity of the conditions that both drugs are designed to treat.

Patients with epilepsy can experience seizures if they miss doses of their TOPAMAX® therapy. Patients who are on TOPROL-XL® therapy run the risk of heart attack or experiencing angina if they interrupt their drug therapy.

The companies involved have alerted medical professionals nationwide of the problem by letter. They are also establishing direct contact between national pharmacy chains and state and national pharmacy groups. The companies will also issue recommendations to drug information database managers to create “pop-up” alerts regarding the potential for errors.
 
Ortho-McNeil Neurologics, Inc. has also offered the following suggestions to physicians: are urged to:

• Be alert to the possibility of medication errors in patients prescribed either TOPAMAX® or TOPROL-XL®.
• Be aware of the possibility of medication errors in any patients presenting with unexpected signs or symptoms while on TOPAMAX® or TOPROL-XL®.
• When either drug is prescribed, confirm the brand and generic names and dosage prescribed on written and oral prescriptions.
• When dealing with these drugs in particular, print legible prescriptions that include the brand and generic names, with indication.
• Counsel patients specifically about the brand name, indication, and proper use of each medication.

In addition, pharmacists are being urged to:

• Separate the two drugs from one another on the stock shelf.
• Place the shelf-talker provided in the Dear Pharmacist communication on the stock shelf.
• Be sure to confirm the brand and generic names prescribed on written and oral prescriptions when either of these drugs is involved.
• Confirm the brand and generic names when communicating the drug names within the pharmacy.
• Write full and legible prescriptions for these products and communicate oral prescriptions clearly.
• Counsel patients about the brand name, indication, and proper use of each medication.

Drug database content providers are urged to:

• Install sound-alike/look-alike name alert warnings for the name pair confusion.
• Use "tall man" lettering to highlight the end of each name.
•  Avoid the use of confusing or non-distinguishing drug mnemonics such as "TOP."
• Use brand and generic names when communicating the drug names.

Finally, patients should:

• Get printed information about the medication from the pharmacist when picking up a prescription for either drug.
• Become better informed about their medications by knowing the brand name of each medication, what the medications looks like, and what side-effects they may experience.
• Look at the medication before they take it. If it does not look like what they usually take, they should contact their healthcare professional immediately to find out why.
• Keep medications in the original, labeled containers to help identify each pill and follow proper directions.
• Ask their healthcare professional for more information if they have any questions about their medications, including the benefits and risks.

Medical professionals who encounter any medication error involving TOPAMAX® should report them immediately to Ortho-McNeil Neurologics, Inc., at 1-800-682-6532, and, if TOPROL-XL® is involved, also to AstraZeneca at 1-800-236-9933.