Table 2.

Other Key Safety Findings, 1997–2007

Product	Indication studied	Finding per FDA medical reviewer
Betamethasone and Betamethasone/ Clotrimazole	Atopic dermatitis	Diprolene AF cream: 32% of children <13 years of age treated for atopic dermatitis had HPA axis suppression. Diprosone: HPA axis suppression with each formulation: cream—23% (2yr–12yr); ointment—28% (6mo–12yr); and lotion—73% (6yr–12yr) Lotrisone: 40% of 12–16-year-olds treated for tinea pedis, and 47% of 12–16-year-olds treated for tinea cruris demonstrated adrenal suppression by cosyntropin testing.
Budesonide	Asthma	A dose-dependent effect on growth was observed. Pneumonia was observed more frequently (3 vs. 0) in patients treated with Pulmicort.
Calcitriol	Hypocalcemia management in patients on hemodialysis	Transient hypercalcemia was seen in 1 of 16 calcitriol-treated patients; 6 of 16 (38%) calcitriol-treated patients and 2 of 19 (11%) placebo-treated patients had Ca × P >75.
Celecoxib	JRA	Celecoxib should be used only with caution in patients with systemic onset JRA due to the risk for serious adverse reactions, including the risk of disseminated intravascular coagulation.
Ciprofloxacin	Complicated UTI, acute pyelonephritis	Not drug of first choice due to increased adverse events compared with controls, including events related to joints and/or surrounding tissues.
Desflurane	Anesthesia	Higher rates of coughing, laryngospasm, and secretions: respiratory AE in 39%, and 5% of children exposed to desflurane experienced severe laryngospasm.
Ertapenem	Anti-infective	Not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration.
Fentanyl	Management of chronic pain	Duragesic should be administered to children only if they are opioid-tolerant and aged 2 years or older.
Fluticasone	Corticosteroid-responsive dermatoses	Cutivate: In a study of 35 pediatric patients treated for atopic dermatitis, subnormal adrenal function was observed with cosyntropin stimulation testing.
Irinotecan	Refractory tumors	Accrual for phase 2 study with 21 children with previously untreated rhabdomyosarcoma halted due to high rate (23.6%) of progressive disease and early deaths (14%).
Isotretinoin	Severe recalcitrant nodular acne	An increased incidence of back pain, arthralgia, and myalgia observed in pediatric patients. In a study of pediatric patients given a single course of therapy, 7.9% had decreases in lumbar spine BMD >4%, 10.6% had decreases in total hip BMD >5% (both adjusted for body mass index).
Lamotrigine	Adjunctive therapy for partial seizures	Approximately 11.5% of the 1081 pediatric patients who received the drug as adjunctive therapy in clinical trials discontinued treatment because of an AE.
Leflunomide	JRA	14/74 patients experienced ALT and/or AST elevations.
Levofloxacin	Anti-infective	In a prospective, long-term, surveillance study, levofloxacin-treated children had a significantly higher incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared with non–fluoroquinolone-treated children.
Linezolid	Anti-infective	Use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended: therapeutic concentrations were not consistently achieved or maintained in the CSF.
Midazolam	Sedation/anxiolysis/ amnesia	Identified a subpopulation (children with congenital heart disease and pulmonary hypertension) at higher risk for AEs and the need to start therapy at the lower end of the dosing range.
Mometasone	Corticosteroid responsive dermatoses/ allergic rhinitis	Elocon cream and ointment: evidence of HPA axis suppression in pediatric patients 6–23 months of age. Elocon lotion: should not be used for the treatment of diaper dermatitis.
Pimecrolimus	Atopic dermatitis	Not recommended for use in children <2 years of age. Infants on Elidel cream had an increased incidence of infections compared with vehicle.
Propofol	Anesthetic	Propofol is not indicated for pediatric ICU sedation as safety has not been established; in a multicenter trial, the incidence of mortality (causality not established) was 9% in the propofol arm versus 4% in the standard sedative agents arm.
Sirolimus	Prevention of rejection after renal transplantation	The use of sirolimus in combination with calcineurin inhibitors and corticosteroids was associated with an increased risk of deterioration of renal function, lipid abnormalities, and urinary tract infections.
Sotalol	Arrhythmias	Smaller children (BSA < 0.33 m2) showed tendency for larger change in QTc and increased frequency of prolongation of the QTc interval, as well as greater beta-blocking effects.

AE =adverse event, BSA = body surface area, CSF = cerebrospinal fluid, HPA = hypothalamic–pituitary–adrenal, ICU = intensive care unit, JRA = juvenile rheumatoid arthritis, UTI = urinary tract infection.