Impact of the 2017 FDA Contraindication on Codeine and Tramadol Dispensing to Children and Adolescents

Background: On April 20, 2017, the Food and Drug Administration (FDA) issued an expanded contraindication against the use of codeine for all children < 12 years, and a new contraindication against the use of tramadol for all children < 12 years and after tonsillectomy/adenoidectomy for adolescents <18 years old, due to the risks of respiratory depression and death. The objective of this study was to determine the change in codeine and tramadol dispensing for treatment of pain to children < 18 years following enactment of the FDA contraindication.

Methods: Using IQVIA Longitudinal Prescription Data (accounts for >90% of retail outpatient opioid prescriptions for pain in U.S.; excludes cough/cold formulations), we extracted monthly counts of unique patients by age group ( < 12yo, 12-17yo) and drug type (codeine, tramadol) from January 2014 to December 2018. Interrupted time series segmented Quasi-Poisson regression was used to evaluate the effectiveness of the contraindication on rates of codeine and tramadol dispensing to children in each age group, by examining pre-contraindication (January 2014-April 2017), contraindication month (May 2017; first full month following contraindication) and post-contraindication (June 2017-December 2018) time periods. We controlled for seasonality and secular trends by including fixed effects for quarters.

Results: From January 2014 to December 2018, codeine prescriptions were dispensed to 1,877,102 children < 12yo and 2,184,045 adolescents 12-17yo, and tramadol prescriptions were dispensed to 490,023 children < 12yo and 955,613 adolescents 12-17yo. For codeine, the mean dispensing rate (per 100,000 persons) for < 12yo decreased from 84.4 pre-contraindication to 23.74 post-contraindication and for 12-17yo decreased from 167.2 pre-contraindication to 102.6 post-contraindication. For <12yo, codeine dispensing rates decreased pre-contraindication (RR=0.98; CI: 0.97-0.99), had a significantly larger decrease during the contraindication month (RR=0.74; CI: 0.69, 0.84), and continued to decrease in the post-contraindication period (RR=0.94, CI: 0.93, 0.96). For 12-17yo, codeine dispensing rates were stable pre-contraindication, decreased significantly in the contraindication month (RR=0.84, CI: 0.77, 0.95), and continued to decrease post-contraindication (RR=0.98, CI: 0.97, 0.99). For tramadol, the mean dispensing rate (per 100,000 persons) for < 12yo decreased from 19.0 pre-contraindication to 12.4 post-contraindication and for 12-17yo decreased from 72.3 pre-contraindication to 46.6 post-contraindication. For both age groups, tramadol dispensing rates decreased pre-contraindication (RR=0.99, CI: 0.99, 0.99), but did not change significantly in the contraindication month or post-contraindication period.

Conclusion: The 2017 FDA contraindication led to an immediate and sustained decrease in codeine dispensing rates for both children and adolescents, though this effect was not seen with tramadol. However, codeine and tramadol continue to be dispensed despite known safety risks in this population, highlighting the need for further interventions.