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Didanosine-induced hypertriglyceridemia
BRIEF CLINICAL
Didanosine-Induced Hypertriglyceridemia
OBSERVATIONS
Subsequently, we noted a decrease in his triglyceride levels and an increase of his liver enzyme values. At this point, gemfibrozil administration was stopped and treatment with didanosine was resumed, which resulted in an increase in triglyceride levels from 289 mg/dL to 524 mg/dL in 2 days. Didanosine was discontinued again and the patient was observed after the didanosine and gemfibrozil therapies were both stopped; at this time, a decrease in his triglyceride levels and a decrease in his liver enzyme values were noted. The overall incidence of pancreatitis among patients receiving didanosine is about 1% to 2% [3]. In addition, certain patients have clinically silent elevation of triglycerides or amylase without other abnormalities. Although increased triglyceride levels are frequently observed in patients with human immunodeficiency virus infection [4], our patient demonstrated a strong cause-effect relationship between the didanosine and the elevated triglyceride levels. Since differentiating between didanosine-induced pancreatitis and that from underlying causes could be difficult, the elevation of triglyceride levels is a possible explanation. Moreover, it may be a useful warning sign prior to the event of clinical pancreatitis. Therefore, it may be prudent to temporarily discontinue didanosine treatment in patients who develop a new elevation of triglyceride levels and to search for other underlying causes.
ALEXANDER TAL, M.D., LAWRENCEDALL, M.D., University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
Didanosine (2’3’-dideoxyinosine; dd1) is indicated for the treatment of adults and children with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex who develop intolerance to or clinical-immunologic deterioration with zidovudine therapy. Pancreatitis is the most serious toxicity of didanosine [1,2]. Although the pathogenesis of didanosine-induced pancreatitis is not known at present, we would like to consider didanosine-induced hypertriglyceridemia as a possible cause for pancreatitis. A 40-year-old man with AIDS who developed intolerance to zidovudine after 8 weeks of treatment was switched to 600 mgld of didanosine. His triglyceride levels rose from 155 mg/dL to 1,630 mg/dL (Table I). There was no elevation in amylase levels, the patient was not taking any other medications, and clinically he was asymptomatic. A sonogram of the pancreas and the biliary system was unremarkable. Didanosine was discontinued and gemfibrozil was introduced at a dose of 600 mg twice a day. TABLE I Didanosine-Induced Hypertriglyceridemia AST B-42
U/L)*
ALT (O-55 U/L)*
AlkalinePhosphatase (37-107
u/L)*
Triglycerides (30-200 mg/dL)*
Cholesterol (120-200 mg/dL)*
Comments
January20,1992
59
53
108
155
113
Startdidanosine
March 18, 1992
20
30
156
1,630
240
Stop didanosine, start gemfibrozil
March 27,1992
163
388
473
449
213
April 3, 1992
990
488
526
399
-
Stop gemfibrozil
April 15, 1992
190
168
329
289
171
Resumedidanosine
April 17, 1992
83
96
250
524
172
Stop didanosine
May 8,1992 44 33 I AST = aspartate transaminase; ALT = alanine transaminase. *Normal values.
177
217
117
Terminate medications
3.Yarchoan
REFERENCES 1. Lambert JS, Seidlin M, Reichman RC, et al. 2’3’-dideoxyinosine (ddl) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. N Engl J Med 1990; 322: 133340.
R, Mitsuya
H, Thomas
RV. et al. In viva activity
against
HIV
and favorable toxicity profile of 2’3’-dideoxyinosine, Science 1989; 245: 412-5. 4. Grunfeld C, Kotler DP. Hamadeh R, eta/. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 1989; 86: 27-31.
2. Yarchoan R, Pluda JM, Thomas RV, et a/. Long-term toxicity/activity profile of 2’3’-dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990; 336: 526-9.
Submitted
August
1993
The American
September
Journal
15, 1992, and accepted in revised form November 19. 1992
of Medicine
Volume
95
247
Didanosine-Induced Hypertriglyceridemia
OBSERVATIONS
Subsequently, we noted a decrease in his triglyceride levels and an increase of his liver enzyme values. At this point, gemfibrozil administration was stopped and treatment with didanosine was resumed, which resulted in an increase in triglyceride levels from 289 mg/dL to 524 mg/dL in 2 days. Didanosine was discontinued again and the patient was observed after the didanosine and gemfibrozil therapies were both stopped; at this time, a decrease in his triglyceride levels and a decrease in his liver enzyme values were noted. The overall incidence of pancreatitis among patients receiving didanosine is about 1% to 2% [3]. In addition, certain patients have clinically silent elevation of triglycerides or amylase without other abnormalities. Although increased triglyceride levels are frequently observed in patients with human immunodeficiency virus infection [4], our patient demonstrated a strong cause-effect relationship between the didanosine and the elevated triglyceride levels. Since differentiating between didanosine-induced pancreatitis and that from underlying causes could be difficult, the elevation of triglyceride levels is a possible explanation. Moreover, it may be a useful warning sign prior to the event of clinical pancreatitis. Therefore, it may be prudent to temporarily discontinue didanosine treatment in patients who develop a new elevation of triglyceride levels and to search for other underlying causes.
ALEXANDER TAL, M.D., LAWRENCEDALL, M.D., University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
Didanosine (2’3’-dideoxyinosine; dd1) is indicated for the treatment of adults and children with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex who develop intolerance to or clinical-immunologic deterioration with zidovudine therapy. Pancreatitis is the most serious toxicity of didanosine [1,2]. Although the pathogenesis of didanosine-induced pancreatitis is not known at present, we would like to consider didanosine-induced hypertriglyceridemia as a possible cause for pancreatitis. A 40-year-old man with AIDS who developed intolerance to zidovudine after 8 weeks of treatment was switched to 600 mgld of didanosine. His triglyceride levels rose from 155 mg/dL to 1,630 mg/dL (Table I). There was no elevation in amylase levels, the patient was not taking any other medications, and clinically he was asymptomatic. A sonogram of the pancreas and the biliary system was unremarkable. Didanosine was discontinued and gemfibrozil was introduced at a dose of 600 mg twice a day. TABLE I Didanosine-Induced Hypertriglyceridemia AST B-42
U/L)*
ALT (O-55 U/L)*
AlkalinePhosphatase (37-107
u/L)*
Triglycerides (30-200 mg/dL)*
Cholesterol (120-200 mg/dL)*
Comments
January20,1992
59
53
108
155
113
Startdidanosine
March 18, 1992
20
30
156
1,630
240
Stop didanosine, start gemfibrozil
March 27,1992
163
388
473
449
213
April 3, 1992
990
488
526
399
-
Stop gemfibrozil
April 15, 1992
190
168
329
289
171
Resumedidanosine
April 17, 1992
83
96
250
524
172
Stop didanosine
May 8,1992 44 33 I AST = aspartate transaminase; ALT = alanine transaminase. *Normal values.
177
217
117
Terminate medications
3.Yarchoan
REFERENCES 1. Lambert JS, Seidlin M, Reichman RC, et al. 2’3’-dideoxyinosine (ddl) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. N Engl J Med 1990; 322: 133340.
R, Mitsuya
H, Thomas
RV. et al. In viva activity
against
HIV
and favorable toxicity profile of 2’3’-dideoxyinosine, Science 1989; 245: 412-5. 4. Grunfeld C, Kotler DP. Hamadeh R, eta/. Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 1989; 86: 27-31.
2. Yarchoan R, Pluda JM, Thomas RV, et a/. Long-term toxicity/activity profile of 2’3’-dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990; 336: 526-9.
Submitted
August
1993
The American
September
Journal
15, 1992, and accepted in revised form November 19. 1992
of Medicine
Volume
95
247