Pediatric rehydration formulary under review

March 15, 2010

Pharmacy and Therapeutics committees around the country are taking a second look at what they're using for pediatric rehydration and how much they're willing to pay.

Pharmacy and Therapeutics Committees around the country are taking another look at pediatric rehydration. The occasion is a push by Baxter Healthcare to expand the use of recombinant hyaluronidase (Hylenex, Baxter) for subcutaneous rehydration from adults to pediatric patients. Most hospitals that use hyaluronidase for pediatric rehydration use more familiar animal-based products such as Hydase (hyaluronidase, PrimaPharm).

Both the animal and recombinant products have similar mechanisms of action. Hyaluronidase depolymerizes hyaluronan, a viscous component of the interstitial space that inhibits bulk fluid flow. The newly permeable interstitial space allows for subcutaneous fluid administration. Subcutaneous rehydration is typically used in patients who cannot accept oral rehydration fluids or who cannot take intravenous fluids due to small or collapsed blood vessels. Up to 15% of children admitted to the emergency department with moderate dehydration are unable to take oral fluids and need parenteral rehydration.

The basic concern is cost, he continued. The recombinant product costs between $40 and $45 more per dose than the standard animal-derived hyaluronidase obtained through the University of Kentucky hospital buying group.

"We have been very pleased with the clinical results so far," he said. "But if we used Hylenex 400 or 500 times a year, it would have a major impact on our budget. At this point, we are restricting Hylenex to monitored pediatric use in the emergency department. We tend to go to central lines for adults who need emergency rehydration."

The push to extend Hylenex into the pediatric population stems from an open-label phase 4 trial involving 51 children; results were published in Pediatrics in October 2009.

The single-arm trial was conducted in nine U.S. emergency departments between August 2007 and June 2008. All the patients had mild-to-moderate dehydration that required parenteral treatment. Patients received a single injection of 1-mL Hylenex (150 U) followed by subcutaneous infusion of isotonic fluid at 20 mL/kg for the first hour and continuing as needed for up to 72 hours.

Of the 51 patients, 48 (94.15%) were rehydrated primarily (five) or totally (43) using subcutaneous fluid. There were no treatment-related systemic events, but there was one case of infusion-site cellulitis that was treated successfully with antibiotics. Investigators reported that the procedure was easy to perform in 49 patients (96%), and 90% of parents were satisfied or very satisfied with the treatment and outcomes.

"The majority of children's hospitals are looking at recombinant hyaluronidase," Kuhn said. "It is not universally accepted. We started developing our protocol over the summer."

At this point, the university formulary authorizes Hylenex only for children in the emergency department who have already failed two attempts at intravenous access and a third attempt by a senior emergency department nurse. That resulted in use two or three times per month during the last quarter of 2009. The current protocol is set for reevaluation every 6 months, Kuhn added.