Aprotinin

  • broad spectrum serine protease inhibitor, with particular inhibition of plasmin (along with trypsin and kallikrein)
  • manufactured in the 1960s by Bayer and has been primarily used in medicine for preventing blood loss during major surgery and promoting soft tissue healing after surgery (as a component of “fibrin glue”)
  • strongly basic polypeptide with half life of approximately 7 hours
  • strong inhibitor of MMPs, including the collagenases
  • MOA – inhibition of the plasmin-activation pathway of the MMPs
  • Doses – 4.2 to 8.5mg used to inject tendons
  • Side effects:  anaphylaxis

Evidence

  • one trial sowed that aprotinin injections were superior to both corticosteroid and saline injections in patellar tendinopathy but the results reported for similar treatment in Achilles tendinopathy have been mixed
  • double blind placebo trials: 
    • study by Capasso et al.  involved athletes being injected every other week with two to four injections for patellar tendinopathy and reported superior results for aprotinin at 12 months follow-up (72% good or excellent) compared to both cortisone (59%) and saline injections (28%). 
    • A study by Brown et al. using aprotinin injections for Achilles tendinopathy reported no improvement over saline and local anesthetic injection.
  • power of the study was low, with the aprotinin group achieving generally greater improvement on raw values

Advantages and Disadvantages

  • polidocanol sclerotherapy, inert agents, or dry needling to treat tendinopathy requires tendon penetration in order to get a beneficial effect, which theoretically increases the risk of tendon damage.  Aprotinin can be injected around the tendon (in the same fashion as cortisone) so the risk of iatrogenic tendon damage is reduced
  • aprotinin is derived from bovine lungs, hence there is the potential to contract bovine spongiform encephalopathy (BSE)
  • off-label treatment for tendinopathy
  • restricted availability of aprotinin as a treatment

References

  1. Brown R., Orchard J., Kinchington M., Hooper A., Nalder G.  Aprotinin in the management of Achilles tendinopathy:  a randomized controlled trial.  Br J Sports Med 2006; 40: 275-279.
  2. Capasso G., Maffulli N., Testa V., Sgambato A.  Preliminary results with peritendinous protease inhibitor injections in the management of Achilles tendinitis.  J Sports Traumatol Rel Res.  1993; 15: 37-40.