Post-marketing studies finding adverse events in drugs used in children

Sep 02, 2008

The Food and Drug Administration Modernization Act (FDAMA, 1997), designed to stimulate more drug safety studies in children, has resulted in more than 130 label changes since its inception nearly six years ago, according to researchers at Duke Children's Hospital. Their analysis appears in the September issue of Pediatrics.

Under this and subsequent renewal of this legislation, pharmaceutical companies were given a six-month extension of their exclusive marketing rights on a drug if they performed clinical trials requested by the FDA to determine the drugs' safety, dosing, and efficacy in children.

According to P. Brian Smith, MD, an assistant professor in Duke's department of pediatrics, many safety concerns cannot be detected until after the introduction of a product to a larger and more diverse population. The Best Pharmaceuticals for Children Act (2002) required the FDA to review and report to a public expert panel the adverse events occurring after granting pediatric exclusivity. That effort was needed because pediatric clinical trials are notoriously small, making it more likely that some safety concerns would not be detected until after the drug is used in a larger pediatric population.

Using MedWatch, the FDA's computerized information database for collecting reports of adverse events, the FDA's Pediatric Advisory Committee reviewed 67 drugs granted the extension. "This is a voluntary, cost-effective reporting system that can identify adverse events that may never have been seen in a clinical trial," Smith said.

"Just because a drug goes through testing and clinical trials does not mean its entire safety profile is known," says Danny Benjamin, MD, a co-author of the study and pediatrician at Duke Children's Hospital. "Before this incentive, there was no systematic, focused pediatric review of the data provided to the FDA's adverse event reporting system. Now, field experts in pediatrics are evaluating the data. That's what's so unique about this effort."

The majority of the 67 drugs studied (65.7 percent) did not appear to cause enough adverse events to require continued pediatric monitoring. However, nearly one in five drugs studied required label changes consisting of additional warnings and cautions for use in children, and several of the adverse events revealed during this process were considered life threatening. Some of those labeling changes included:

-- Black Box warning and development of patient information for selective serotonin reuptake inhibitors (SSRIs) regarding potential for suicidality and neonatal toxicity/withdrawal syndrome.

-- Box warning for transdermal opioid analgesis (Duragesic) alerting that inappropriate use may result in serious adverse reactions, including death.

-- Labeling change for methylphenidate (Concerta) to address the potential for psychiatric events.

The Duke researchers say their findings support the approach that pediatric post-marketing surveillance is crucial, and that physicians, nurses, parents and others should take the job of reporting adverse effects seriously. Very rare serious adverse events are seldom defined during a study of a few hundred children and learning about these events is often dependent on the reporting of them from caretakers and parents.

"Unfortunately, few clinicians and patients know this reporting system exists," says Smith. "In the Duke Neonatal Intensive Care Unit, the pharmacist reports adverse drug events to MedWatch. But I'm not sure that happens at every hospital. A lot of physicians don't know it's available. This publication is somewhat of an advertisement that this program is available."

Smith urges parents to report adverse reactions they see. The FDA does not release any confidential information provided. Nor do the parents have to be certain that a drug exposure was the cause. It's the FDA's job to further investigate these events and any possible relationships to therapy, Smith said.

Source: Duke University

Explore further: Drug research and development more efficient than expected

add to favorites email to friend print save as pdf

Related Stories

Keeping hackers out of hospitals

Jan 07, 2015

The humble infusion pump: It stands sentinel in the hospital room, injecting patients with measured doses of drugs and writing information to their electronic medical records.

Adverse drug events costly to health care system: research

Feb 25, 2011

Patients who suffer an adverse medical event arising from the use or misuse of medications are more costly to the health care system than other emergency department (ED) patients, say physicians and research scientists at ...

Recommended for you

Drug research and development more efficient than expected

Feb 27, 2015

Drug R&D costs have increased substantially in recent decades, while the number of new drugs has remained fairly constant, leading to concerns about the sustainability of drug R&D and question about the factors that could ...

Use new meningitis vaccines only for outbreaks

Feb 26, 2015

(AP)—A U.S. panel on Thursday recommended that two new meningitis vaccines only be used for rare outbreaks, resisting tearful pleas to give it routinely to teens and college students.

New antibiotic avycaz approved

Feb 26, 2015

(HealthDay)—The combination antibiotic Avycaz (ceftazidime-avibactam) has been approved by the U.S. Food and Drug Administration to treat adults with complicated infections of the intra-abdominal area or urinary tract, ...

Tagging drugs to fight counterfeit medicines

Feb 25, 2015

The U.S. and other countries are enacting rules to clamp down on the sales of fake pharmaceuticals, which pose a public health threat. But figuring out a system to track and authenticate legitimate drugs still faces significant ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.