Oxandrolone (OxandrinOxandrolone (Oxandrin®®) ) and the Risk of and the Risk of Peliosis HepatisPeliosis Hepatis

Troy Kish, Pharm.D.Troy Kish, Pharm.D.Pharmacy Practice Resident (PGY-1)Pharmacy Practice Resident (PGY-1)

Department of PharmacyDepartment of PharmacyKingsbrook Jewish Medical CenterKingsbrook Jewish Medical Center

Brooklyn, NYBrooklyn, NY

Clinical Instructor of Pharmacy Practice Clinical Instructor of Pharmacy Practice Arnold & Marie Schwartz College of Pharmacy andArnold & Marie Schwartz College of Pharmacy and

Health Sciences of Long Island UniversityHealth Sciences of Long Island UniversityBrooklyn, NYBrooklyn, NY

Peliosis Hepatis (PH) DefinedPeliosis Hepatis (PH) Defined

Blood filled cysts ranging from <1 cm to Blood filled cysts ranging from <1 cm to several centimeters in sizeseveral centimeters in size

Seen in parenchymal cellsSeen in parenchymal cellsOften occurs in liver, but can also develop Often occurs in liver, but can also develop

in lung, spleen, bone marrow, and lymph in lung, spleen, bone marrow, and lymph nodesnodes

Peliosis HepatisPeliosis Hepatis

Causes of PHCauses of PH

IdiopathicIdiopathicKidney or heart transplantationKidney or heart transplantationHIVHIVMalignancyMalignancy

Hodgkin’sHodgkin’sMultiple myelomaMultiple myeloma

BacterialBacterialBartonella spp.Bartonella spp.

Drug Induced PHDrug Induced PH

Androgenic-anabolic steroidsAndrogenic-anabolic steroidsTamoxifen (NolvadexTamoxifen (Nolvadex®®))Oral contraceptivesOral contraceptivesAzathioprineAzathioprineCorticosteroidsCorticosteroidsArsenicArsenic

Overview of Overview of Oxandrolone (OxandrinOxandrolone (Oxandrin®®))

Synthetic testosterone derivativeSynthetic testosterone derivative1717ββ-hydroxy-17-hydroxy-17αα-methyl-2-oxa-5-methyl-2-oxa-5αα--

androstan-3oneandrostan-3one1/6 of testosterone’s androgenic activity1/6 of testosterone’s androgenic activity6.3x anabolic activity of methyltestosterone6.3x anabolic activity of methyltestosterone

Indications for Oxandrolone UseIndications for Oxandrolone Use

Adjunctive therapy to promote weight gain Adjunctive therapy to promote weight gain in patients who:in patients who:Undergo extensive surgeryUndergo extensive surgeryHave chronic infectionsHave chronic infectionsSuffer severe traumaSuffer severe traumaFail to maintain normal weightFail to maintain normal weight

Offset corticosteroid induced protein Offset corticosteroid induced protein catabolism in chronic therapycatabolism in chronic therapy

Relief of bone pain associated with Relief of bone pain associated with osteoporosisosteoporosis

Reports of PH with Androgen TherapyReports of PH with Androgen TherapyPatientPatient DrugDrug Total Dose Total Dose

(g)(g)

DurationDuration

(months)(months)

DeathDeath

70 yo M70 yo M OxymetholoneOxymetholone 2222 1919 YesYes

64 yo F64 yo F OxymetholoneOxymetholone 55 1.51.5 YesYes

31 yo F31 yo F Oxymetholone;Oxymetholone;

Methyltestost-Methyltestost-eroneerone

1414

n/an/a

33

44

YesYes

74 yo M74 yo M Oxymetholone; Oxymetholone; TestosteroneTestosterone

1010

n/an/a

1010

1313

YesYes

68 yo F68 yo F OxymetholoneOxymetholone 4141 1818 YesYes

1 yo M1 yo M OxymetholoneOxymetholone 5656 1717 YesYes

31 yo M31 yo M OxymetholoneOxymetholone 3030 77 YesYes

Nadell et al Arch Pathol Lab Med 1977;101:405-410

Reports of PH with Androgen TherapyReports of PH with Androgen Therapycont….cont….

PatientPatient DrugDrug Total Dose Total Dose

(g)(g)

DurationDuration

(months)(months)

DeathDeath

41 yo M41 yo M OxymetholoneOxymetholone 1414 66 YesYes

27 yo M27 yo M TestosteroneTestosterone

OxymetholoneOxymetholone

86862020

141466

YesYes

50 yo F50 yo F OxymetholoneOxymetholone 3535 1111 YesYes

n/a Mn/a M FluoxymesteroneFluoxymesterone n/an/a n/an/a YesYes

24 yo M24 yo M OxymetholoneOxymetholone 33 4848 YesYes

Nadell et al Arch Pathol Lab Med 1977;101:405-410

Reports of PH with Androgen TherapyReports of PH with Androgen Therapycont….cont….

PatientPatient DrugDrug Total Dose Total Dose

(g)(g)

DurationDuration

(months)(months)

DeathDeath

67 yo M67 yo M11 OxymetholoneOxymetholone ~143~143 2424 NoNo

54 yo M54 yo M22 Unknown “sex Unknown “sex hormone pill”hormone pill”

n/an/a n/an/a YesYes

3 FA pts3 FA pts33

1 non-FA1 non-FA

OxymetholoneOxymetholone 4, 3, 1.5 (g/kg)4, 3, 1.5 (g/kg)

0.7 (g/kg)0.7 (g/kg)

n/an/a 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

Oxandrolone and PHOxandrolone and PH

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

Clinical ApplicationClinical Application

Baseline monitoring parametersBaseline monitoring parametersAST, ALT, bilirubin, alkaline phosphataseAST, ALT, bilirubin, alkaline phosphataseMonitor Monitor weeklyweekly following therapy initiation following therapy initiation

Continually assess need for therapyContinually assess need for therapyPatient’s weight, nutritional status, wound sizePatient’s weight, nutritional status, wound size

Adjust dose in renal dysfunctionAdjust dose in renal dysfunctionStart at 5 mg BID when CrCl <60 mL/min or Start at 5 mg BID when CrCl <60 mL/min or

patient on dialysispatient on dialysis