Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management.

IMPORTANCE OF THE FIELD: Hyaluronidase for injection is an adjuvant that increases the absorption and dispersion of other injected drugs or fluids (hypodermoclysis); and improves absorption of radiopaque agents in subcutaneous urography. Ovine hyaluronidase is approved for the treatment of vitreous hemorrhages. AREAS COVERED IN THIS REVIEW: We review approved indications for injectable hyaluronidase and off-label uses as well as safety, efficacy and dosing information. We compare formulations made using animal tissue extracts versus the novel human recombinant type. Emphasis is on the human recombinant form and off-label uses in patients with chronic pain. WHAT THE READER WILL GAIN: Hyaluronidase reduces the obstacle that the interstitial matrix presents to fluid and drug transfer. It is a mucolytic enzyme derived from mammalian tissue or synthesized in vitro in pure form (rHuPH20) using recombinant technology. Hyaluronidase is used off-label in chronic pain management to facilitate removal of epidural adhesions with mechanical and/or hydrostatic forces and to treat edema. TAKE HOME MESSAGE: The recently introduced rHuPH20 formulation obviates any risk of allergic reaction or prion-related illnesses. Reduction of edema by hyaluronidase and facilitation of epidural adhesioloysis may be beneficial in treating certain chronic painful conditions.