The Narrow Margin - Revisited

Photo Credit – Wikipedia

 

# 9427

 

Earlier this year the FDA imposed long awaited new limits on the amount of acetaminophen (APAP) allowed in prescription opioid/APAP prescriptions like Vicodin and Lorcet to 325mg in order to reduce the risk of liver damage in patients taking these meds for chronic pain. 

 

Over the counter (OTC) formulations, however, continue to be sold in both the regular 325mg and `extra strength’  500 mg doses, and APAP is commonly found in scores of multi-ingredient  `cold remedies’,  increasing opportunities for consumers to inadvertently `double-up’ on their consumption of the drug.

 

While well tolerated when taken as directed, APAP in larger doses is a hepatotoxin; it overwhelms and destroys the liver. In fact, APAP poisoning is the biggest cause of acute liver failure in the United States (cite).

 

A study published in 2011 in the American Journal of Preventive Medicine (see Emergency Department Visits for Overdoses of Acetaminophen-Containing Products) found that - in the United States alone – there are an estimated 78,414 ER visits each year due to acetaminophen (aka Tylenol, paracetamol, APAP) poisoning.

 

Although most of these were intentional overdoses (69.8%), more than 13,000 ER visits were described as due to `therapeutic misadventures’  . . . or accidental overdoses.

 

The problem with acetaminophen is that there is a relatively narrow margin between the maximum therapeutic dose and a potentially toxic (and sometimes fatal) overdose. 

Add in the concurrent consumption of alcohol – common during the holidays – and you further exacerbate its toxicity.

 

With last week’s warning (see CDC: Early Data Suggests Potentially Severe Flu Season) a lot of people will be turning to OTC medications from their home medicine cabinet for symptom relief.  Which is why each year  I try to do a piece on some of the hidden dangers of these commonly used medications.  

 

• In Kids, Colds, And OTC Meds we looked at the continuing trend of parents – against the advice of the CDC  – to use OTC medications to treat cold and flu symptoms in toddlers under the age of four.

• And the year before, we looked at inconsistent and confusing dosing instructions provided by many manufacturers of OTC medications (see JAMA: Inconsistent Dosing Instructions For OTC Meds).

• Another study in 2010 (see Inappropriate Use Of OTC Medicines In Children) reported that inappropriate use, and incorrect dosing of OTC meds lead to a large number of accidental drug poisonings each year.

Unfortunately, accidental and intentional poisonings from OTC medications are all too common. In October of 2012 the AAC  (Acetaminophen Awareness Coalition) launched a Know Your Dose campaign to help educate consumers about the safe use of the popular pain reliever.

Credit – Acetaminophen Awareness Coalition

 

For parents whose young children are ill,  the impulse  to `do something’  to alleviate their misery is particularly strong.  But all medicines - even those available over-the-counter – have risks.  And for very small children, the FDA and the CDC  believe those risks outweigh any benefit they might derive from these types of products.

 

This Q& A from the CDC.

 

Questions and Answers for Parents about Over-the-Counter (OTC) Medicines

For adults, over-the-counter pain relievers, decongestants and saline nasal sprays may help relieve some symptoms. Remember, always use over-the-counter products as directed.

For children, over-the-counter pain relievers, decongestants and saline nasal sprays may help relieve some symptoms. Not all products are recommended for children of certain ages.

These medicines may help relieve symptoms such as runny nose, congestion, fever and aches, but they do not shorten the length of time you or your child is sick.

Q: What pain relievers can I give my child?

A: For babies 6 months of age or younger, parents should only give acetaminophen for pain relief. For a child 6 months of age or older, either acetaminophen or ibuprofen can be given for pain relief. Be sure to ask your child’s healthcare provider for the right dosage for your child’s age and size. Do not give aspirin to your child because of Reye's syndrome, a rare but very serious illness that harms the liver and brain. Learn more about Reye’s syndrome.

Q: Should parents give cough and cold medicines to young children?

A: The Consumer Healthcare Products Association (CHPA), a group that represents most of the makers of nonprescription over-the-counter (OTC) cough and cold medicines, recommends that these products not be used in children under 4 years of age. The Food and Drug Administration (FDA) supports this recommendation. Overuse and misuse of OTC cough and cold medicines in young children can result in serious and potentially life-threatening side effects.

Q: What can parents do to help their children feel better if they are too young to take cough and cold medicines or the healthcare provider advises against using them?

A: Parents might consider clearing nasal congestion in infants with a rubber suction bulb. Also, a stuffy nose can be relieved with saline nose drops or a clean humidified or cool-mist vaporizer.

Q: Should parents give cough and cold medicines to children over 4 years of age?

A: Cough and cold symptoms usually go away without treatment after a certain amount of time. Over-the-counter cough and cold medicines will not cure the common cold, but may give some temporary relief of symptoms. Parents should consult their child’s healthcare provider if they have any concerns or questions about giving their child a medication. Parents should always tell their child’s healthcare provider about all prescription and over-the-counter medicines they are giving their child.

Q: What should parents and doctors be careful of if they want to give cough and cold medicines to children over 4 years of age?

A: Always keep medications in original bottles or containers, with the cap secure, and up and away from children. Children getting into and taking medications without adult supervision can lead to serious and potentially life-threatening effects. Avoid giving more than one cough and cold medicine at a time to children. Two medicines may have different brand names but may contain the same ingredient. Some cough and cold medicines contain more than one active ingredient. Also, follow directions carefully to avoid giving too much medication; the right amount of medication often depends on your child’s age and weight.

 

For more on this topic, parents may want to check out the CDC’s Cold and Cough Medicines: Information for Parents.

The Perils Of Not Knowing Your Dose

Photo Credit – Wikipedia

 

 

# 7837

 

Twice last year (see The Narrow Margin & Too Much Of A Good Thing ) we looked at the dangers of accidental (& intentional) overdoses of acetaminophen (Tylenol ®).  

 

The first blog looked at a national campaign called KNOW YOUR DOSE launched by the AAC  (Acetaminophen Awareness Coalition), while the second looked at Supratherapeutic Dosing of Acetaminophen Among Hospitalized Patients – where a study found doctors were sometimes prescribing more than the recommended daily dose of acetaminophen for their patients.

 

Doctors will typically prescribe  hydrocodone/APAP 5 mg/500 mg 1 to 2 tablets every 4 to 6 hours to give patients some latitude in pain control. If a patient takes the full prescribed dose (12 pills in 24 hours) they will ingest 6 g of acetaminophen, or 50% more than the maximum daily recommendation.

 

In 2011 the FDA announced their intention to limit the amount of acetaminophen in opioid/APAP prescriptions like Vicodin and Lorcet to 325mg in order to reduce the risk of liver damage in patients taking these meds for chronic pain. But those regulations won’t come into effect until January of 2014, and for now, 500 mg & 600 mg APAP/opioid analgesics are still available.

 

But it isn’t just misuse of prescription medicines containing acetaminophen, as there are more than 600 over-the-counter medications containing the drug, and people who take two or more of these cold/pain remedies are often unaware of how much of the drug they are ingesting.

 

A study published in 2011 in the American Journal of Preventive Medicine (see Emergency Department Visits for Overdoses of Acetaminophen-Containing Products) found that - in the United States alone – there are an estimated 78,414 ER visits each year due to acetaminophen (aka Tylenol, paracetamol, APAP) poisoning.

 

Although most of these were intentional overdoses (69.8%), more than 13,000 ER visits were described as due to `therapeutic misadventures’  . . . or accidental overdoses.

The problem with acetaminophen is that there is a narrow margin between the maximum therapeutic dose and a potentially toxic (and sometimes fatal) overdose. 

 

While well tolerated when taken as directed, APAP in larger doses is a hepatotoxin; it overwhelms and destroys the liver. In fact, APAP poisoning is the biggest cause of acute liver failure in the United States (cite).

Which is why Johnson & Johnson – the makers of Extra-Strength Tylenol ® – has announced that they will take the unusual step of printing (In bright red letters) a warning on the bottle caps of their product.

More information on the safe  use of acetaminophen appears on the Johnson & Johnson website: 

 

Acetaminophen —the active ingredient in TYLENOL^® — is an effective pain reliever and fever reducer. It works quickly and safely when used as directed.

Here is some information on the appropriate use of TYLENOL^®:

• Always read and follow the label
• Don't take TYLENOL^® with other products containing acetaminophen
• Don't exceed the recommended dosage
• Don't take TYLENOL^® if you drink 3 or more alcoholic beverages a day
• Talk to your doctor if you are taking the blood-thinning drug, warfarin

 

 

With cold and flu season upon us, the consumption of over the counter (OTC) remedies will most certainly go up considerably over the next few months, so it seems a good time to repeat the warning from the ACC  KNOW YOUR DOSE campaign.

 

And finally, we’ve these videos from the FDA’s  Youtube channel on the dangers of misusing acetaminophen.

 

 

 

Too Much Of A Good Thing

Photo Credit – Wikipedia

 

# 6714

 

Today we’ve a bit of a follow up to a blog I wrote last month called The Narrow Margin that looked at the dangers of accidental overdosing with acetaminophen (APAP) which is an ingredient found in more than 600 prescription, and non-prescription, drugs.

 

While well tolerated and safe at normal doses, too much acetaminophen can cause liver damage, and even death. The maximum safe dose for an adult under 65 is considered to be 4g in 24 hours (3g for those over 65, or those with liver problems).

 

In October the AAC  (Acetaminophen Awareness Coalition) launched a Know Your Dose campaign to help educate consumers about the safe use of the popular pain reliever.

 

Credit – Acetaminophen Awareness Coalition

 

The problem goes beyond the public’s mixing and matching over-the-counter medications, as some doctors will typically prescribe  hydrocodone/APAP 5 mg/500 mg 1 to 2 tablets every 4 to 6 hours to give patients some latitude in pain control.

 

If a patient takes the full prescribed dose (12 pills in 24 hours) they will ingest 6 g of acetaminophen, or 50% more than the maximum daily recommendation.

 

In 2011 the FDA announced their intention to limit the amount of acetaminophen in opioid/APAP prescriptions like Vicodin and Lorcet to 325mg in order to reduce the risk of liver damage in patients taking these meds for chronic pain. 

 

Those regulations won’t come into effect until January of 2014, and for now, 500 mg & 600 mg APAP/opioid analgesics are common.

 

Which brings us to a study today in the Archives Of Internal Medicine called:

Supratherapeutic Dosing of Acetaminophen Among Hospitalized Patients

Li Zhou, MD, PhD; Saverio M. Maviglia, MD, MS; Lisa M. Mahoney, RPh; Frank Chang, MSE; E. John Orav, PhD; Joseph Plasek, MS; Laura J. Boulware; Hong Lou; David W. Bates, MD, MSc; Roberto A. Rocha, MD, PhD

Arch Intern Med. 2012;():1-8. doi:10.1001/2013.jamainternmed.438.

 

 

This study, which looked at the records of more than 23,000 patients at two Boston hospitals during the summer of 2010, and found that 14,411 patients during the study period were administered acetaminophen.

 

Nearly a thousand of those (n=955, or 6.6%) received more than the the 4g daily maximum dose.  Perhaps even more telling, 22.3% of patients older than 65, and 17.6% of patients with chronic liver disease exceeded the 3g/day limit.

 

No cases of liver toxicity were reported among these patients, although some patients did experience significant elevations of at least one liver enzyme (alkaline phosphatase). The authors caution, however, that a `causal relationship cannot be concluded’.

 

Patients receiving more than one acetaminophen containing drug, and those in surgical and intensive care units, were most likely to exceed the daily maximum dosage of APAP.

 

All of which shows that, even in a hospital setting, it is all too easy to exceed the 4 g/day APAP maximum dose.

 

The phasing in of lower APAP levels in opioid-combo  analgesics over the next year should go a long ways towards reducing this problem, as would better health information technology systems designed to catch such overdoses, and alert the nursing staff.

 

Until then (and even after) it is always a good idea to be proactive and ask what meds you (or someone in your care) is being given in a hospital, and to speak up if you suspect their might be a problem.

 

For more on this story, you may wish to check out this report from Reuter’s Health.

 

Many hospital patients get too much Acetaminophen

By Genevra Pittman

NEW YORK | Tue Nov 13, 2012 12:36pm EST

The Narrow Margin

Photo Credit – Wikipedia

 

# 6649

 

 

Cold and flu season is upon us, and that means the consumption of over the counter (OTC) remedies will go up considerably over the next few months. So each fall I try to do a piece on some of the hidden dangers of these commonly used medications.  

 

• Last year, in Kids, Colds, And OTC Meds we looked at the continuing trend of parents – against the advice of the CDC  – to use OTC medications to treat cold and flu symptoms in toddlers under the age of four.

 

• And the year before, we looked at inconsistent and confusing dosing instructions provided by many manufacturers of OTC medications (see JAMA: Inconsistent Dosing Instructions For OTC Meds).

 

• Another study in 2010 (see Inappropriate Use Of OTC Medicines In Children) reported that inappropriate use, and incorrect dosing of OTC meds lead to a large number of accidental drug poisonings each year.

 

 

The plain truth is, accidental and intentional poisonings from OTC medications are very common.

 

A study published last year in the American Journal of Preventive Medicine (see Emergency Department Visits for Overdoses of Acetaminophen-Containing Products) found that - in the United States alone – there are an estimated 78,414 ER visits each year due to acetaminophen (aka Tylenol, paracetamol, APAP) poisoning.

 

While most of these were intentional overdoses (69.8%), more than 13,000 ER visits were described as due to `therapeutic misadventures’  . . . or accidental overdoses.

 

The problem with acetaminophen is that there is a narrow margin between the maximum therapeutic dose and a potentially toxic (and sometimes fatal) overdose. 

 

While well tolerated when taken as directed, APAP in larger doses is a hepatotoxin; it overwhelms and destroys the liver. In fact, APAP poisoning is the biggest cause of acute liver failure in the United States (cite).

 

Since more than 600 products (OTC and Rx) contain acetaminophen, many consumers may be unaware that they could be `doubling up’ their dose when they take two or more of them. 

 

All of which leads me to a press release issued earlier this week by the AAC  (Acetaminophen Awareness Coalition)  who have launched a Know Your Dose campaign to help educate consumers about the safe use of acetaminophen. 

 

Excerpts below, but follow the links to read them in their entirety.

 

Credit – Acetaminophen Awareness Coalition

 

 

U.S. Health Coalition Reminds Consumers: Double Check, Don't Double Up

As Cold and Flu Season Nears, Consumers Are Urged to Double Check Their Medicine Labels to Avoid Doubling Up on Acetaminophen

WASHINGTON, Oct. 17, 2012 /PRNewswire-USNewswire/ --

The Acetaminophen Awareness Coalition is launching a nationwide initiative today calling on consumers to double check their medicine labels so they don't double up on medicines that contain acetaminophen during the cold and flu season. Acetaminophen is the most common drug ingredient in America. It is found in more than 600 different medicines, including prescription (Rx) and over-the-counter (OTC) pain relievers, fever reducers, sleep aids and numerous cough, cold and flu medicines. It is safe and effective when used as directed, but there is a limit to how much can be taken in one day. Taking more than directed is an overdose and can lead to liver damage.

 

Each year, Americans catch an estimated one billion colds, and as many as 20 percent get the flu. Seven in 10 consumers use over-the-counter medicines, many of which contain acetaminophen, to treat their symptoms. The Coalition is targeting its "Double Check, Don't Double Up" message to the more than 50 million Americans who use acetaminophen weekly for conditions such as headache and chronic pain, and directing them to double check their medicine labels before taking a cold or flu medicine that also contains acetaminophen.

 

<SNIP>

When taking medicines for cough, cold or flu this coming season, consumers should follow these four simple acetaminophen safety steps:

1. Know if medicines contain acetaminophen, which is in bold type or highlighted in the "active ingredients" section of over-the-counter medicine labels and sometimes listed as "APAP" or "acetam" on prescription labels.
2. Never take two medicines that contain acetaminophen at the same time.
3. Always read and follow the medicine label.
4. Ask your healthcare provider or a pharmacist if you have questions about dosing instructions or medicines that contain acetaminophen.

(Continue . . . )

 

For more on this issue, we turn to the FDA’s  Youtube channel for the following videos.

 

 

 

 

 

 

While drugs like acetaminophen are extremely useful and safe when taken as directed, the number of ER visits each year testify to the harm they can do when taken inappropriately.