Safety of ibuprofen in infants younger than six months: A retrospective cohort study

OBJECTIVE: We hypothesized (1) that gastrointestinal (GI) and renal adverse events (AE) would occur more often in infants first prescribed ibuprofen before rather than after six months of age and (2) that ibuprofen would be associated with more adverse effects than acetaminophen in infants younger than six months. METHODS: We created two partly overlapping retrospective cohorts of infants aged less than six months when California Medicaid first paid for ibuprofen or acetaminophen between 2004 and 2010. In the first cohort we compared the incidence rate ratio (RR) of GI and renal AE between those infants first prescribed ibuprofen before six months of age with those first prescribed ibuprofen after six months of age. In the second cohort we compared the RR of GI and renal AE between infants younger than six months prescribed ibuprofen (+/-acetaminophen) with those prescribed only acetaminophen. RESULTS: We identified 41,669 prescriptions for ibuprofen and 176,991 prescriptions for acetaminophen in 180,333 eligible infants (median age 2.1 months). We did not observe higher RR of any AE in infants first prescribed ibuprofen before rather than after six months of age. Most infants prescribed ibuprofen were also prescribed acetaminophen. Any GI (adjusted (a)RR 1.25, 95% CI 1.13–1.38) and moderate or severe GI AE (aRR 1.24, 95% CI 1.09–1.40) were more common in infants younger than six months who were prescribed ibuprofen versus acetaminophen alone. Severe GI (aRR 0.63, 95% CI 0.27–1.45) and renal AE (aRR 1.84 95% CI 0.66–5.19) were not different between the ibuprofen (+/-acetaminophen) and acetaminophen-only groups. CONCLUSIONS: GI and renal AEs were not higher in infants younger than six months who were prescribed ibuprofen compared with those aged six to 12 months. AEs were increased in infants younger than six months who were prescribed ibuprofen compared with infants who were prescribed acetaminophen alone.