Book Description

Background: Prescribing medications for an indication or age outside of the terms of U.S. Food and Drug Administration (FDA) approval is called off label prescribing. In children, off label prescribing has resulted in drug disasters and increased adverse events and has been the subject of recent legislation promoting medication study. Off label prescribing appears to be a very common pediatric practice; nonetheless, the pharmacoepidemiology of off label prescribing has not been systematically studied and could inform approaches to interventions. Methods: The National Ambulatory Medical Care Surveys (NAMCS), a nationally representative population based sample of U.S. outpatient medical visits collected by the Centers for Disease Control and Prevention (CDC) were utilized over a four year period (2001 2004). We evaluated an estimated 312 million prescription visits by children 0-17 years old (based on a sample of 7901 prescription visits). FDA approved age and indication were compared to the to the child's age and diagnoses. Descriptive and regression analyses were used to determine epidemiological characteristics and predictors of: (1) pediatric off label prescribing in general, (2) prescribing to infants and toddlers (0-3 yrs; n=81 million visits) and (3) off label prescribing for age versus off label prescribing for indication. Results: Sixty two percent of U.S. outpatient pediatric prescription visits included off label prescribing, with 25% (95% CI: 23%, 27%) including off label prescribing for age and 53% (95% CI: 50%, 56%) off label prescribing for indication. Approximately 96% of cardiovascular renal, 86% of pain, 80% of gastrointestinal, and 67% of pulmonary and dermatologic prescriptions were off label. Anti infectives, upper respiratory and pulmonary medications were much more commonly prescribed off label for indication (41%, 52%, and 61%) than for age (6%, 16%, and 24%). For infants and toddlers, off label prescribing occurred in 65% of prescription visits (52.7 million), with a higher risk of exposure to off label prescribing for age than older children. Physician specialists were 14% (95% CI: 7%, 20%) more likely to prescribe off label for age than general pediatricians or family physicians. Most top prescribed off label medications have remained unchanged over time. Conclusions: Despite legislation resulting in studies and labeling changes of pediatric medications, the majority of pediatric outpatient visits involve off label prescribing, across all medication categories, to the youngest children, especially by physician specialists, and with medications that are off label for indication; this exposure is disproportionate compared to adults. Many off label prescriptions are for medications with unproven benefit or safety concerns. FDA policies should be strengthened to require prioritized study of all medications commonly prescribed off label; mandate patient registries to assess off label prescribing over time; and provide physicians more accessible prescribing information. Medical education and prescribing incentives and tools should target the most commonly off label prescribed drugs. Future research should determine outcomes, causes, and appropriateness of off label prescribing to children.