Drugs Given to Children at U.S. Hospitals Are Mostly Off-Label

March 8, 2007

PHILADELPHIA -- Nearly 80% of hospitalized children are medicated with drugs that have not been approved by the FDA for pediatric use, according to a study here.

PHILADELPHIA, March 8 -- Nearly 80% of hospitalized children are medicated with drugs that have not been approved by the FDA for pediatric use, according to a study here.

"Though off-label drug use also occurs in adults, the problem is substantially greater in children because many drugs have not been tested in any pediatric population for any indication," said Samir S. Shah, M.D., of the Children's Hospital of Philadelphia.

Central and autonomic nervous system drugs, such as morphine, were the most common to be given off-label, Dr. Shah and colleagues reported in the March issue of Archives of Pediatric and Adolescent Medicine. Such drugs were given to 66% of the hospitalized children.

The study examined only off-label use by age, not indication, so the results "likely underestimate the magnitude of off-label drug use in children," the investigators said.

They analyzed records from the Pediatric Health Information System database on more than 355,000 children 18 or younger admitted to 31 U.S. hospitals during 2004. The investigators focused on 90 drugs thought to be administered frequently to children or recommended for further study in children by the FDA. Key results include:

  • At least one drug was used off-label in 297,592 patients (78.7%).
  • Off-label pediatric use was highest with autonomic and central nervous system drugs, including morphine (given to 27.8% of children), fentanyl (Actiq) (23.2%), and midazolam (Versed) (19.6%).
  • Gastrointestinal drugs and fluids and nutrients were also given to children relatively often. Such drugs include ondansetron (Zofran) (given to 24.8% of pediatric patients) ranitidine (Zantac) (17.7%), and potassium chloride (16%).
  • Antineoplastic and diagnostic drugs were the least prescribed off-label to children. The studied drugs in this category were vincristine (given to 1.8% of children) and dactinomycin (Cosmegen) (0.2%). These drugs tend to be well studied in children and have more pediatric indications from the FDA, the investigators said.
  • Children undergoing surgical procedures were more than 20-times more likely to receive a drug off-label than those in the hospital for other reasons (odds ratio=21.8; 95% CI=9.4 to 50).

The study participants were 55% male, 51% white, 21% black, and 16% Hispanic. But gender and racial differences were not associated with overall off-label drug use, the study found.

More severe illness, as assessed by case mix index (CMI), was also associated with off-label pediatric use. The average CMI for those receiving an off-label drug was 1.83, compared with 0.98 for those who not receiving an off-label drug (P