1. Oxandrolone (Oxandrin ® ) and the Risk of Peliosis Hepatis Troy Kish, Pharm.D. Pharmacy Practice Resident (PGY-1) Department of Pharmacy Kingsbrook Jewish Medical Center Brooklyn, NY Clinical Instructor of Pharmacy Practice Arnold & Marie Schwartz College of Pharmacy and Health Sciences of Long Island University Health Sciences of Long Island University Brooklyn, NY

2. Peliosis Hepatis (PH) Defined Blood filled cysts ranging from <1 cm to several centimeters in size Blood filled cysts ranging from <1 cm to several centimeters in size Seen in parenchymal cells Seen in parenchymal cells Often occurs in liver, but can also develop in lung, spleen, bone marrow, and lymph nodes Often occurs in liver, but can also develop in lung, spleen, bone marrow, and lymph nodes

3. Peliosis Hepatis

4. Causes of PH Idiopathic Idiopathic Kidney or heart transplantation Kidney or heart transplantation HIV HIV Malignancy Malignancy Hodgkin’s Hodgkin’s Multiple myeloma Multiple myeloma Bacterial Bacterial Bartonella spp. Bartonella spp.

5. Drug Induced PH Androgenic-anabolic steroids Androgenic-anabolic steroids Tamoxifen (Nolvadex ® ) Tamoxifen (Nolvadex ® ) Oral contraceptives Oral contraceptives Azathioprine Azathioprine Corticosteroids Corticosteroids Arsenic Arsenic

7. Overview of Oxandrolone (Oxandrin ® ) Synthetic testosterone derivative Synthetic testosterone derivative 17β-hydroxy-17α-methyl-2-oxa-5α- androstan-3one 17β-hydroxy-17α-methyl-2-oxa-5α- androstan-3one 1/6 of testosterone’s androgenic activity 1/6 of testosterone’s androgenic activity 6.3x anabolic activity of methyltestosterone 6.3x anabolic activity of methyltestosterone

8. Indications for Oxandrolone Use Adjunctive therapy to promote weight gain in patients who: Adjunctive therapy to promote weight gain in patients who: Undergo extensive surgery Undergo extensive surgery Have chronic infections Have chronic infections Suffer severe trauma Suffer severe trauma Fail to maintain normal weight Fail to maintain normal weight Offset corticosteroid induced protein catabolism in chronic therapy Offset corticosteroid induced protein catabolism in chronic therapy Relief of bone pain associated with osteoporosis Relief of bone pain associated with osteoporosis

9. Reports of PH with Androgen Therapy PatientDrug Total Dose (g)Duration(months)Death 70 yo M Oxymetholone2219Yes 64 yo F Oxymetholone51.5Yes 31 yo F Oxymetholone; Methyltestost- erone 14n/a34Yes 74 yo M Oxymetholone; Testosterone 10n/a1013Yes 68 yo F Oxymetholone4118Yes 1 yo M Oxymetholone5617Yes 31 yo M Oxymetholone307Yes Nadell et al Arch Pathol Lab Med 1977;101:405-410

10. Reports of PH with Androgen Therapy cont…. PatientDrug Total Dose (g)Duration(months)Death 41 yo M Oxymetholone146Yes 27 yo M TestosteroneOxymetholone8620146Yes 50 yo F Oxymetholone3511Yes n/a M Fluoxymesteronen/an/aYes 24 yo M Oxymetholone348Yes Nadell et al Arch Pathol Lab Med 1977;101:405-410

11. Reports of PH with Androgen Therapy cont…. PatientDrug Total Dose (g)Duration(months)Death 67 yo M 1 Oxymetholone~14324No 54 yo M 2 Unknown “sex hormone pill” n/an/aYes 3 FA pts 3 1 non-FA Oxymetholone 4, 3, 1.5 (g/kg) 0.7 (g/kg) n/an/a 1.Arnold et al American Journal of Gastroenterology 1979 ; 71:213-216 2.Yap et al Ann Acad med Singapore 1993;22(3):381-383 3.Altay Clin Genet 1997;51:296-302 FA= Fanconi’s Anemia

12. Oxandrolone and PH MEDLINE search from 1964 to 2009 using search terms “Peliosis hepatis” and “Oxandrolone” yielded 0 reports MEDLINE search from 1964 to 2009 using search terms “Peliosis hepatis” and “Oxandrolone” yielded 0 reports

13. Clinical Application Baseline monitoring parameters Baseline monitoring parameters AST, ALT, bilirubin, alkaline phosphatase AST, ALT, bilirubin, alkaline phosphatase Monitor weekly following therapy initiation Monitor weekly following therapy initiation Continually assess need for therapy Continually assess need for therapy Patient’s weight, nutritional status, wound size Patient’s weight, nutritional status, wound size Adjust dose in renal dysfunction Adjust dose in renal dysfunction Start at 5 mg BID when CrCl <60 mL/min or patient on dialysis Start at 5 mg BID when CrCl <60 mL/min or patient on dialysis