Dosing Recommendations for Pediatric Patients With Renal Impairment

Abstract

A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the clinical evidence behind current renal impairment dosage recommendations for pediatric patients in a standard pediatric dosing handbook. The sources of recommendations and comparisons included the pediatric dosing handbook (Lexicomp), the U.S. Food and Drug Administration-approved manufacturer's labels, and published studies in the literature. One hundred twenty-six drugs in Lexicomp had pediatric renal dosing recommendations. Only 14% (18 of 126) of Lexicomp pediatric renal dosing recommendations referenced a pediatric clinical study, and 15% of manufacturer's labels (19 of 126) described specific dosing regimens for renally impaired pediatric patients. Forty-two products had published information on pediatric renal dosing, but 19 (45%) were case studies. When pediatric clinical studies were not referenced in Lexicomp, the renal dosing recommendations followed the adult and pediatric dosing recommendations on the manufacturer's label. Clinical evidence in pediatric patients does not exist for most renal dosing recommendations in a widely used pediatric dosing handbook, and the adult renal dosing recommendations from the manufacturer's label are currently the primary source of pediatric renal dosing information.

Keywords: MIDD (model-informed drug development); drug development; pediatrics (PED); renal disease; special populations.

Figure 1.

Breakdown for the 126 drugs with dosing recommendations for pediatric populations with renal impairment, as identified from the Lexicomp Pediatric and Neonatal Dosage Handbook, 25th edition. Information was collected from a review of the FDA-approved manufacturer’s label (left), the Lexicomp Pediatric Handbook (center), and the literature (right).

Figure 2.

Therapeutic areas for drugs containing specific dosing recommendations for a pediatric population with renal impairment in either the Lexicomp Pediatric Handbook (gray) or on the manufacturer’s label (black). The number at the top of the bar is the total for that therapeutic area, and the lower number is the black bar count. Drugs listed in the “Other” class include acrivastine (antihistamine), anakinra (immunosuppressant), azathioprine (immunosuppressant), deferasirox (iron-chelating agent), gadopentetate (contrast agent), miglustat (substrate reduction therapy), and tranexamic acid (antifibrinolytic).