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.

 

 

 

Kids, Colds, And OTC Meds

 

 

# 5878

 

With cold and flu season on the way, this is probably a good time to remind my readers that the CDC and the FDA continue to warn parents over the use of many over-the-counter (OTC) cough and cold medications in young children.

 

In January of 2008 the FDA issued a warning to parents that OTC cough and cold remedies were no longer considered to be safe or effective for children  under the age of 2.

 

Public Health Advisory: FDA Recommends that Over-the-Counter (OTC) Cough and Cold Products not be used for Infants and Children under 2 Years of Age

FDA has completed its review of information about the safety of over-the-counter (OTC) cough and cold medicines in infants and children under 2 years of age.  FDA is recommending that these drugs not be used to treat infants and children under 2 years of age because serious and potentially life-threatening side effects can occur.

(Continue . . . )

 

 

Despite this announcement, the debate over the safety and effectiveness of these same medications for older children continued, with some experts calling to ban their use for children under the age of 6.

 

In a bit of a pre-emptive strike, in the fall of 2008 the CHPA (Consumer Healthcare Products Association ) announced that its members were voluntarily modifying the product labels on many of their OTC meds to state "do not use" in children under 4 years of age. 

 

Despite these recommendations, and the publicity they generated, old habits apparently die hard.

 

Earlier this year the C.S. Mott Children’s Hospital National Poll on Children’s Health indicated that for a majority of parents, those warnings are going unheeded.

 

 

The following excerpts are from the University of Michigan Health System’s press release:

 

February 14, 2011

ANN ARBOR ,Mich.

Parents continue to give cough and cold meds to young kids, despite FDA warnings

Research has linked over-the-counter cough and cold products to poisoning or death in hundreds of children, ages 2 and younger. Studies have also shown that these medicines do little to control symptoms. As a result, in 2008, the United States Food and Drug Administration formally recommended that OTC cough and cold products not be given to children under age 2.

 

A poll released today by the C.S. Mott Children’s Hospital National Poll on Children’s Health shows that 61-percent of parents of children, ages 2 and younger, gave their children OTC cough and cold medicine within the last 12 months. The poll also shows that more than half of parents report that their child’s doctor says OTC cough and cold medications are safe for children under 2; half of their physicians said they are effective.

(Continue . . . )

 

 

For parents, watching their child suffer from a cold or flu can be very difficult, and so the impulse  to `do something’ to alleviate their misery is 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 from the CDC.

 

Cold and Cough Medicines: Information for Parents

It's winter, and parents may be tempted to reach for over-the-counter medicines to ease their child's sniffling and coughs. But recent safety concerns have prompted drug manufacturers to change their labels stating that cough and cold medicines should NOT be given to children younger than age 4. Parents can take some steps now to help keep their children safe.

 

Each year, thousands of children under age 12 go to emergency rooms after taking over-the-counter cough and cold medicines. Most of these children were unsupervised when they took the medicine.

 

In response to safety concerns, the leading manufacturers of children's cough and cold medicines are voluntarily changing the labels on these products to state that they should not be used in children younger than 4 years of age.

(Continue . . .)

 

Adding to the risks, in December of 2010 we saw a study (see JAMA: Inconsistent Dosing Instructions For OTC Meds) demonstrating the dangerously ambiguous labeling of measuring devices, and inconsistent instructions, on many cough and cold medicines.

 

And in August of last year (see Inappropriate Use Of OTC Medicines In Children) a study was presented at the International Pharmaceutical Federation’s (FIP) conference in Lisbon, Portugal (Aug 28th-Sept 2nd), on the widespread parental misuse of over-the-counter (OTC) medicines for children.

 

The question remains, what can a parent do to help relieve their child’s symptoms without resorting to potentially harmful OTC meds?

 

Again the CDC has some suggestions that may help.

 

Symptom Relief

• How to Feel Better
• Over-the-Counter (OTC) Medicines
• Questions and Answers for Parents about Over-the-Counter (OTC) Medicines
• Related Materials

Poll: Despite FDA Warning Parents Use OTC Cold Remedies For Kids Under 2

 

 

 

# 5319

 

In January of 2008 the FDA issued a warning to parents that OTC (over-the-counter) cough and cold remedies were no longer considered to be safe or effective for children  under the age of 2.

 

 

Public Health Advisory: FDA Recommends that Over-the-Counter (OTC) Cough and Cold Products not be used for Infants and Children under 2 Years of Age

FDA has completed its review of information about the safety of over-the-counter (OTC) cough and cold medicines in infants and children under 2 years of age.  FDA is recommending that these drugs not be used to treat infants and children under 2 years of age because serious and potentially life-threatening side effects can occur.

(Continue . . . )

 

Despite these recommendations, and the publicity they generated, old habits apparently die hard.

 

 

Three years later the C.S. Mott Children’s Hospital National Poll on Children’s Health indicates that for a majority of parents, those warnings are going unheeded.

 

 

 

The following excerpts are from the University of Michigan Health System’s press release:

 

February 14, 2011

ANN ARBOR ,Mich.

Parents continue to give cough and cold meds to young kids, despite FDA warnings

Research has linked over-the-counter cough and cold products to poisoning or death in hundreds of children, ages 2 and younger. Studies have also shown that these medicines do little to control symptoms. As a result, in 2008, the United States Food and Drug Administration formally recommended that OTC cough and cold products not be given to children under age 2.

 

A poll released today by the C.S. Mott Children’s Hospital National Poll on Children’s Health shows that 61-percent of parents of children, ages 2 and younger, gave their children OTC cough and cold medicine within the last 12 months. The poll also shows that more than half of parents report that their child’s doctor says OTC cough and cold medications are safe for children under 2; half of their physicians said they are effective.

 

(Continue . . . )

 

 

Particularly concerning is the assertion by roughly half of the parents that their healthcare providers continue to recommend these products for their children under the age of 2.

 

The safety and effectiveness of OTC cold remedies for children between the ages of 2 and 6 is still under review by the FDA.  

 

Complicating matters, in December we saw a study (see JAMA: Inconsistent Dosing Instructions For OTC Meds) demonstrating the ambiguous labeling of measuring devices, and inconsistent instructions, on many cough and cold medicines.

 

And in August 2010 (see Inappropriate Use Of OTC Medicines In Children) a study was presented at the International Pharmaceutical Federation’s (FIP) conference in Lisbon, Portugal (Aug 28th-Sept 2nd), on the widespread parental misuse of over-the-counter (OTC) medicines for children.

 

For parents, watching their child suffer from a cold or flu can be very difficult, and so the impulse is to `do something’ to alleviate their misery is strong.   

 

But all medicines . . . even those available over-the-counter – have risks.  And for very small children, the FDA believes those risks outweigh any benefit they might derive from these types of products.

JAMA: Inconsistent Dosing Instructions For OTC Meds

 

 

# 5104

 

 

Imagine you purchase a bottle of liquid medicine and the instructions on the box tell you to take 2 tablespoons (30mL) every 4 hours and give your 6 year-old child 1 tablespoon (15mL) every four hours.  

 

The handy measuring device provided by the manufacturer looks like this:

 

Figure 2 from the JAMA study

Nowhere on this measuring cup are there Tablespoon markings. . .  only teaspoons, and mL. 

 

And the largest measurement – 4tsp - isn’t even a recommended dose.  It is too much for a child, and not enough for an adult.

 

Of course, you may consider yourself lucky. Some medicines don’t even provide a measuring device. 

 

Welcome to the confusing world of inconsistent OTC (Over-the-Counter) drug dosing instructions.

 

And while you might consider yourself capable of doing the mental conversion gymnastics in your head, not everyone is equally medically astute.

 

Besides . . any bleary-eyed, stressed out, and sleep deprived parent ladling out medicine to a sick child in the middle of the night can be subject  to confusion - particularly when the instructions are less than perfectly clear.

 

In the fall of 2009, the FDA and the Consumer Health Products Association (CHPA) each released similar new voluntary guidelines for the packaging and dosing instructions of liquid medications, particularly those intended for use by children.

 

The FDA’s recommendations were pretty simple, with the main ones being:

 

• Measuring devices should be included for all over-the-counter liquid medications.
• Devices should be marked with calibrated units of measure that are the same as those specified in the labeled dosage directions.
• Abbreviations used on devices should be the same as those used in directions.
• Devices should not bear extraneous or unnecessary markings.
• Devices should not be significantly larger than the largest dose described.
• Abbreviations should conform to international or national standards.
• Abbreviations should be defined on devices and/or label directions.
• Decimals and fractions should be used with care and conform to recommendations

 

 

While most of these recommendations may seem fairly obvious, apparently they weren’t to the manufacturers.

 

According to this study, nearly all (well, 98.6%) of oral OTC medications examined prior to these guidelines being released contained dosing directions and measuring devices that were `highly variable or inconsistent’.

 

Ambiguities and inconsistencies that could easily lead to the under-dosing or over-dosing of a child with the medication.

 

JAMA has two free articles available on the subject.

 

A study study that takes an eye-opening look at the poorly conceived OTC dosing instructions on 200 popular pediatric oral liquid medications surveyed in 2009, and an editorial on the study.

 

First, a look at the study.  I’ve only posted a snippet from the abstract.  You’ll want to read the whole thing.

 

Evaluation of Consistency in Dosing Directions and Measuring Devices for Pediatric Nonprescription Liquid Medications

H. Shonna Yin, MD, MS; Michael S. Wolf, PhD, MPH, MA; Benard P. Dreyer, MD; Lee M. Sanders, MD, MPH; Ruth M. Parker, MD

JAMA. Published online November 30, 2010. doi:10.1001/jama.2010.1797

Abstract (Excerpts reformatted)

Results Measuring devices were packaged with 148 of 200 products (74.0%).

 

Within this subset of 148 products, inconsistencies between the medication's dosing directions and markings on the device were found in 146 cases (98.6%).

 

These included missing markings (n = 36, 24.3%) and superfluous markings (n = 120, 81.1%).

 

Across all products, 11 (5.5%) used atypical units of measurement (eg, drams, cc) for doses listed.

 

Milliliter, teaspoon, and tablespoon units were used for doses in 143 (71.5%), 155 (77.5%), and 37 (18.5%) products, respectively.

 

A nonstandard abbreviation for milliliter (not mL) was used by 97 products. Of the products that included an abbreviation, 163 did not define at least 1 abbreviation.

 

Conclusion At the time the FDA released its new guidance, top-selling pediatric OTC liquid medications contained highly variable and inconsistent dosing directions and measuring devices.

 

 

You’ll also want to read the accompanying editorial.

 

Ensuring Safe and Effective Use of Medication and Health Care

Perfecting the Dismount

Darren A. DeWalt, MD, MPH

 

 

CHPA, which is a trade association representing U.S. manufacturers and distributors of over-the-counter medicines and nutritional supplements, released a statement yesterday in response to the publication of these two articles in JAMA.

 

You can read it at the link below.

CHPA Statement Outlining Measuring and Dosing Improvements Already Made for Liquid OTC Medicines for Children

 

 

For now, the guidelines issued by CHPA and the FDA are strictly voluntary.

 

It will likely require another study some time in the future to determine how much progress has been made in the adoption of these recommendations.

Inappropriate Use Of OTC Medicines In Children

 

 

# 4850

 

 

From the International Pharmaceutical Federation’s (FIP) conference in Lisbon, Portugal (Aug 28th-Sept 2nd), an illuminating press release on a paper to be presented today on the widespread parental misuse of over-the-counter (OTC) medicines for children.

 

A research team led by Dr. Rebekah Moles of the University of Sydney, New South Wales, reports that the inappropriate use, and incorrect dosing of OTC meds lead to a large number of accidental drug poisonings each year.

 

Running through a  variety of scenarios, nearly 100 adult caregivers were asked to decide what OTC medicines were appropriate for a child given their symptoms, and asked to measure out an appropriate dose.

 

 

A brief excerpt from the press release outlining the abysmal results follows.  By all means, click the link to read it in its entirety.

 

 

Widespread parental misuse of medicines puts children at risk

(Excerpt)

Common OTC medicines were made available, together with different types of dosing devices, including household spoons. Participants then chose whether or not to give a medicine, at what stage, and at what dose. They were asked to measure the dose for the researchers. Because doses for children are often small, the risk of getting the measurement wrong is greatly increased, the researchers say.

 

"Taking all the scenarios together, 44% of participants would have given an incorrect dose, and only 64% were able to measure accurately the dose they intended to give. We found that 15% of participants would give a medicine without taking their child's temperature, and 55% would give medicine when the temperature was less than 38 degrees", said Dr. Moles. Paracetamol was the preferred treatment, even for coughs and cold, and was used most often – 61% of the time – despite the child having no fever. Only 14% of carers managed the fever scenario correctly.

(Continue . . .)