Page 77 - Heart Transplant Protocol

Heart Function Service: Heart Transplant Protocols

Subcutaneous injections should be given at least one inch from an old site and never into areas
where the site is tender, bruised, erythematous or indurated. Consider using the less
concentrated (1mg/ml) concentration for patient experiencing local injection site reaction.

Drug/Herbal Interaction:
Avoid green tea, grapefruit and ascorbic acid

Monitoring parameters:
Signs/symptoms of peripheral neuropathy, dehydration, PRES or hypotension
CBC with differential and platelets
Renal function tests
Pulmonary function tests
Liver function tests

Side effects:
Most common adverse reactions (>20%): nausea, diarrhea, thrombocytopenia, neutropenia,
peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting,
lymphopenia, rash, pyrexia and anorexia.

Toxicology:
A toxic dose has not been established. Overdoses of twice the recommended dose have
resulted in rapid symptomatic hypotension and thrombocytopenia leading to fatal outcomes.
Treatment is symptomatic and supportive.

Reference:
1. Everly MJ, Everly JJ, Susskind B, et al. Proteasome inhibition reduces donor-specific antibody levels. Transplant Proc.
2009;41:105-7.
2. Everly MJ, Everly JJ, Susskind B, et al. Bortezomib provides effective therapy for antibody- and cell-mediated acute
rejection. Transplantation. 2008 27;86:1754-61.
3. Mattingly LH, Gault RA, Murphy WJ. Use of systemic proteasome inhibition as an immune-modulating agent in
disease. Endocr Metab Immune Disord Drug Targets. 2007;7:29-34.
4. Miguel JS, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple
myeloma. NEJM 2008;359:906-17.
5. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients
with relapsed multiple myeloma: a randomized, phase 3, non-inferiority study. Lancet Oncology 2011;12:431-40.
6. National Cancer Institute. National Cancer Institute Cancer Therapy Evaluation Program common terminology criteria
for adverse events, version 4.03. June, 2010. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. (accessed February 13, 2013).
7. Perry DK, Burns JM, Pollinger HS, et al. Proteasome inhibition causes apoptosis of normal human plasma cells
preventing alloantibody production. Am J Transplant 2009 ;9:201-9. Epub 2008 Oct 31.
8. Product Information. VELCADE (bortezomib). Millennium Pharmaceuticals, Inc, Cambridge, MA 02139.
9. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 Study of bortezomib in relapsed, refractory myeloma. NEJM
2003;348:2609-17

Updated November 9, 2017 77