Table 1: Details of 9 reports of symptomatic hepatic dysfunction associated with nefazodone
| Case |
Age/sex |
Dose at time of event and duration
of treatment |
Concomitant medications |
Signs, symptoms and biopsy
findings |
Laboratory test results* |
Intervention |
Outcome† |
| 1 |
42/F |
150 mg/d x 5 wk |
Zopiclone, norethindrone, ethinylestradiol,
sertraline x 9 d (1 wk after nefazodone discontinued) |
Maculopruritic rash, abdominal pain, nausea,
vomiting, conjunctival icterus; biopsy showed drug-induced hepatitis
with secondary intrahepatic cholestasis |
AP 256 U/L, total bilirubin 247 µmol/L |
Nefazodone and sertraline discontinued,
patient admitted to hospital |
Positive dechallenge |
| 2 |
53/F |
100 mg bid x 3 mo |
Clonazepam, flurazepam, trimethotrimeprazine |
Nausea, vomiting, epigastric pain, hepatic cytolysis |
AST 500 U/L, ALT 450 U/L, AP 343 U/L |
Nefazodone discontinued |
Positive dechallenge |
| 3 |
47/F |
150 mg every morning, 300 mg every night x 7-8
mo |
Synthroid, Tylenol #3 as needed |
After 5-6 mo: nausea, weight loss (11-14 kg),
increased fatigue, hair loss After 7-8 mo: anorexia, nausea, vomiting,
further weight loss (2-4kg), jaundice, scleral icterus |
AST 500-700 U/L, ALT 600-900 U/L, GGT 80
U/L, bilirubin 200-300 µmol/L, AP 150-200 U/L, negative for hepatitis
virus A, B and C |
Patient admitted to hospital, nefazodone discontinued,
prednisone initiated |
Jaundice resolved, liver enzyme levels (except
AP) returned to normal |
| 4 |
30/F |
150 mg bid x 4 wk |
None |
Jaundice |
ALT 2258 U/L, negative for hepatitis virus A,
B and C |
Nefazodone discontinued 1 wk after onset
of jaundice |
Positive dechallenge ALT returned to normal |
| 5 |
68/F |
50 mg bid x 6-7 mo |
Conjugated estrogens, medroxyprogesterone |
Anorexia, weight loss (10.4 kg), fatigue, hepatitis,
slight icterus |
AST 375 U/L, ALT 420 U/L, bilirubin 34 µmol/L |
Nefazodone discontinued 3 wk after onset
of symptoms, concomitant medications continued |
Positive dechallenge |
| 6 |
50/F |
NA
5-6 mo
|
NA |
Jaundice, hepatitis confirmed by liver biopsy,
liver necrosis |
Abnormal liver function test results |
Patient admitted to hospital, nefazodone discontinued |
Positive dechallenge |
| 7 |
26/F |
150 mg bid at 4 mo; 150 mg/d at 8 mo
x 8 mo |
Oral contraceptive |
Jaundice, nausea, fatigue, dark urine |
NA |
Nefazodone reduced after first onset of symptoms
(at 4 mo); discontinued after second onset (at 8 mo) |
Positive dechallenge |
| 8 |
NA |
NA |
NA |
Jaundice |
NA |
Nefazodone discontinued |
Positive dechallenge |
| 9 |
35/F |
150 mg bid x 4 wk |
NA |
Nausea |
AST 620 U/L, ALT 1044 U/L, negative for hepatitis
virus A, B and C |
Nefazodone discontinued |
Positive dechallenge |
|
Note: NA = information not available, AP =
alkaline phosphatase, AST = aspartate aminotransferase, ALT = alanine
aminotransferase, GGT = gamma-glutamyl-transferase.
*Normal ranges vary among laboratories; however,
typical reference values are as follows: ALT< 50 U/L, AST
< 40 U/L, total bilirubin < 25 µmol/L, GGT < 49
U/L and AP < 125 U/L.
†Dechallenge = outcome after drug discontinued.
|
