Dosing directions and measuring devices for top-selling pediatric over-the-counter liquid medications were highly inconsistent as of November 2009, when the Food and Drug Administration issued voluntary industry guidelines in response to numerous reports of unintentional overdoses by children, according to a descriptive study of 200 such medications.

Since that time, the Consumer Healthcare Products Association also implemented guidelines for its members addressing some of the issues raised in the study, which it stresses are based on outdated data (Also see "CHPA Adopts Dosing Guidelines For OTC Pediatric Liquids" - Pink Sheet, 7 December, 2009.).

H. Shonna Yin of New York University and colleagues studied 200 OTC liquid medications to provide a baseline for assessing the degree and pace of industry conformity with the new guidelines.

Study Highlights

148 out of 200 OTC liquid drugs include a dosing device
146 liquid OTCs have a measuring device inconsistent with dosing directions
24% of devices are missing markings referenced in directions
81% of devices have extra markings
5.5% of products use atypical measurement units, such as cubic centimeters and drams

They found 146 of 148 medications that included measuring devices had one or more inconsistencies between the dosing directions and the markings on the device, according to the Journal of the American Medical Association study, published online Nov. 30.

The inconsistencies included missing markings in 24% of the products, superfluous markings in 81% of the products and inconsistencies between the product's label and measuring device in 89% of products.

Furthermore, 5.5% of the products used atypical units of measurement, such as cubic centimeters, drams or fluid ounces; 71.5% used milliliters (although 97 products used a nonstandard abbreviation for milliliter); 77.5% used teaspoon units; and 18.5% used the tablespoon.

Other potentially problematic findings included no leading zero in 12.5% of 40 products with a dose smaller than 1 unit presented in decimal format, nonstandard fraction formats in 64.5% of 110 products that used fractions and no warning that the measuring device should be used only with its associated product in 62% of the 148 medications that included a device.

The investigators evaluated 200 products representing 99% of the U.S. market of analgesic, cough/cold, allergy and gastrointestinal OTC liquid products – including 58 private-label products – that contained dosing information for children under age 12. The medications were studied during the 52 weeks ended Oct. 30, 2009.

Researchers Urge More FDA Oversight

"Given the high prevalence of baseline inconsistencies, regulatory oversight may be helpful in accelerating adoption of the guidance recommendations," the investigators write, noting that several Institute of Medicine reports identify variable and poor-quality drug labeling as a major cause of confusion – and therefore, a potential risk factor for unintentional misuse of products (Also see "Drug Industry Avoids FDA's "Blunt Tools" With Safe Use Initiative Progress" - Pink Sheet, 10 May, 2010.).

Indeed, many of the unintentional overdoses that prompted the FDA guidance in 2009 were attributed, at least in part, to products with inconsistent or confusing labels and measuring devices (Also see "FDA Gets Strict On Liquid OTC Dosing Devices In Draft Guidance" - Pink Sheet, 9 November, 2009.).

Elements Of FDA's Guidelines

All OTC liquid medication products include a measuring device.
Measuring devices use consistent abbreviations and units of measurement.
The devices bear only necessary markings and not hold significantly more medication than the largest prescribed dose.
Abbreviations conform to standards and be defined.
Firms use decimals and fractions with care.
Researchers conduct studies on accurate use of the medications by consumers.

The study supports FDA's recommendations because more than half of all U.S. children are exposed to at least one medication in a given week – and more than half of those medications are OTC. Also, at least one in three U.S. adults and at least one in four U.S. parents has limited health literacy and even worse numeracy.

The study underscores the need for standardized measuring devices with all nonprescription liquid products, consistency between dosing directions and markings on the measuring device, and standardization of measurement units, abbreviations and numeric formats across products, Yin and associates say.

"Even frequently used terms like teaspoon and tablespoon may be misinterpreted," they write, noting that errors in understanding teaspoon vs. tablespoon contribute to threefold errors, and that the use of these terms endorses the use of kitchen spoons, which are associated with measurement error.

More patient-centered research is needed to address best practices under the FDA guidance, and to evaluate other aspects of product packaging and safe medication use, they say. They add that because FDA's guidelines are voluntary, subsequent systematic product analyses might help monitor progress of industry compliance – and assess whether additional regulatory oversight is needed to ensure safe and effective use of OTC medications.

Industry Must Improve Communication

Yin and colleagues "document a concerning state of affairs," which underscores the need for health care providers – including pharmaceutical companies – to communicate better with consumers about proper dosing, Darren A. DeWalt says in an editorial accompanying the report.

"Perhaps the most frustrating aspect of this issue of communicating clearly to avoid mistakes is that such communication is not already an integral part of selling pharmaceuticals," says DeWalt, an assistant professor at the University of North Carolina at Chapel Hill School of Medicine.

Drug companies need to clarify the information about indications and dosing for patients. Physicians also need to take some ownership of the problem.

He likens the handoff of responsibility from the health care system to the patient to a dismount in gymnastics, noting that the dismount may be more important than the rest of the routine.

"Most of our time in medical education and professional development is focused on getting the diagnosis and treatment plan right … all that work is meaningless without the dismount, which, in medicine, requires enabling the patient to understand and act in ways to maximize health outcomes," DeWalt says.

He adds, "The dismount for a drug company is taking the information about indications and dose and making it clear for patients. Similar to the rest of the drug development process, the industry should test the usability of dosing devices and instructions to ensure that patients of all health literacy levels can accurately use them."

Advancing patient safety and improving outcomes requires investing more time and resources in practicing and perfecting the dismount.

"It is time to learn to stick the landing," DeWalt concludes.

CHPA Argues Study Data Are Outdated

DeWalt is scoring industry's "landing" while it is still mid-routine, CHPA suggests in a response the same day JAMA released the article.

"These data presented in the JAMA article, while a valuable snapshot of the marketplace one to two years ago, are outdated. They predate industry's voluntary guidelines approved in November 2009 that are already underway."

"In November 2009, CHPA approved voluntary guidelines with respect to liquid OTC medicines," the group notes.

"The guidelines address two important components. The first involves the inclusion of an appropriate dosing device for OTC pediatric medications. CHPA members are in compliance with this guideline."

"The second component involves dosing directions for OTC liquid medications with dosing directions for children under age 12. While the guideline includes such improvements as utilizing charts versus running text for labeled dosing directions and user-friendly formats regarding fractions and decimals, it also suggests use of milliliters as the preferred unit for dosing. … It is our goal that all OTC medicines will fully follow the guidelines by the end of 2011."

CHPA Liquid Dosing Guidelines

Use milliliter alone as dose unit or with teaspoonful unit equivalent
Only use the abbreviations mL or tsp
Do not use abbreviations on labels
Use a leading zero with decimals and express fractions as lower-case math notations
Use a dosing table if space permits
Provide a calibrated dosing device
Use contrasting graduated markings
Match device measurements to instructions

CHPA notes the American Association of Poison Control Centers supports the guidelines, which were developed through the public-private PROTECT Initiative, with the Centers for Disease Control and Prevention and other stakeholders.

PROTECT also suggests industry develop packaging that reduces the risk of unsupervised ingestion by children, such as needle-less syringes, flow restrictors and individually packaged doses (Also see "Acetaminophen Awareness Coalition Prepares To Launch Education Campaign" - Pink Sheet, 22 November, 2010.).

The JAMA study is not "really about whether companies have had a chance to adhere to the guidance. It is about the fact that they needed guidance in the first place," DeWalt said in an e-mail.

He added, "Many of the problems identified by Yin should not have needed any guidance. All of us in health care shouldn't need to be told by regulators how to 'stick the landing.' We need to pay attention and focus on it ourselves."

Finally, DeWalt said, the guidance is only a starting point based on expert opinion. He concluded, "The real message to the industry is to study what makes a label and device work best for the public and design an evidence-based label/device."

The JAMA study was funded by a career development grant to Yin from the Robert Wood Johnson Physician Faculty Scholars Program. Yin also reported receiving funds from Pfizer and McKing Consulting Corp. Other authors on the study said they received funding from Pfizer, Abbott, Johnson & Johnson and/or McKing Consulting. DeWalt disclosed that he has received honoraria and other funding from Pfizer.

[Editor's note: This story appears courtesy of Elsevier Global Medical News.]

By Sharon Worcester

Dosing Directions, Measuring Devices Vary For OTC Meds, JAMA Study Says

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