6. Victorino RMM, Maria VA, Correia AP, de Moura Me. Floxacillininduced cholestatic hepatitis with evidence of lymphocyte sensitization.
Arch Intern Med 1987;147:987-9. 7. Victorino RMM, Hodgson HJR. Relationship between T cell subpopulations and the mitogen responsiveness and suppressor cell function of peripheral blood mononuclear cells in normal individuals. Clin Exp lm-
munoI1980;42:571-8. 8. Larrey D, Henrion J, Heller F, Babany G, Degott C, Pessayre D, et al. Metoprolol-induced hepatitis: rechallenge and drug oxidation phenotyping. Ann Intern Med 1988;108:67-8. 9. Tanner LA, Bosco LA, Zimmerman HJ. Hepatic toxicity after acebutolol therapy. Ann Intern Med 1989;111:533-4. 10. Schwartz MS, Frank MS, Yanoff A, Morecki R. Atenolol-associated cholestasis. Am J Gastroenterol 1989;84:1084-6.
II. Clark JA, Zimmerman HJ, Tanner LA. Labetalol hepatotoxicity. Ann
Intern Med 1990;113:210-3. 12. Shearman DJC, Finlayson NDe. Drugs, toxins and the liver. In: Diseases of the gastrointestinal tract and liver. London: Churchill Livingstone, 1982:527-54. 13. Rotmensch HH, Leiser A, Dan M, Klejman A, Livni E, I\lie B, et al. Evaluation of prajrnalium-induced cholestasis by immunological tests.
Arch Intern Med 1981;141:1797-801. 14. Victorino RMM, Maria V AJ. Modifications of the lymphocyte transformation test in a case of drug-induced cholestatic hepatitis. Diagn Immunol 1985;3:177-81.
PROPAFENONE-INDUCED LIVER INJURY Sarah A. Spinler, Cheryl A. Elder, and K. Elizabeth Kindwall
OBJECTIVE: DFSIGN:
To describe propafenone-induced liver injury.
Retrospective case report.
Referred care in a large tertiary care center. Laboratory tests were performed at the auxiliary site and the tertiary care center.
SETIlNG:
PATIENT: A 71-year-old woman with atrial fibrillation developed elevations of greater than two times the upper limit of normal in alkaline phosphatase (ALK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GOT) after initiation ofpropafenone therapy.
INTERVENTIONS:
Studies included serial measurements of ALK, ALT,
AST, and GOT.
this case, the pattern demonstrated by elevations in liver enzymes may be classified as acute cholestatic liver injury. Because the reported incidence is 0.1-0.2 percent and there are no known fatalities secondary to propafenone liver injury, routine monitoring of liver function tests in all patients receiving propafenone cannot be recommended at this time. Baseline liver function tests prior to initiating propafenone therapy with follow-up laboratory studies one month later are recommended in patients with known liver dysfunction. If elevations are noted, a reduction in dose may result in lower liver enzyme concentrations, although discontinuation of therapy may be required in some cases.
Ann Pharmacother 1992;26:926-8.
The patient developed elevations of greater than two times the upper limit of normal in ALK, ALT, and AST, one month after initiating propafenone therapy. The propafenone dose was decreased from 900 to 675 mg/d and, ten days later, the ALK, AL T, and AST were decreased slightly, but still above the upper limit of normal. One month later, serum transaminases had returned to baseline, but propafenone therapy was discontinued because of recurrent atrial fibrillation, persistent elevation in ALK, and elevation in GOT. Two months after discontinuing propafenone, serum arninotransaminase and ALK concentrations had normalized and GOT had decreased and remained only slightly elevated. RFSULTS:
The occurrence of liver injury secondary to propafenone therapy is rare. Reported cases appear to be secondary to hepatocellular injury, cholestasis, or a combination of the two. In
CONCLUSIONS:
SARAH A. SPINLER, Pharm.D., is an Assistant Professor of Clinical Pharmacy, Philadelphia College of Pharmacy and Science, and an Adjunct Assistant Professor of Pharmacy in Medicine, University of Pennsylvania, Cardiovascular Section, Hospital of the University of Pennsylvania: CHERYL A. ELDER, B.S.Pharm.• is a Pharm.D. Student, Philadelphia College of Pharmacy and Science; and K. ELIZA· BETH KINDW ALL, M.D.. is an Assistant Professor of Medicine, University of Pennsylvania, Cardiovascular Section. Hospital of the University of Pennsylvania. Reprints: Sarah A. Spinier, Pharm.D .• Philadelphia College of Pharmacy and Science, 600 S. 43rd St., Philadelphia. PA 19104.
926
•
The Annals ofPharmacotherapy
•
PROPAFENONE HYDROCHLORIDE is a class IC antiarrhythmic agent indicated for the treatment of life-threatening ventricular arrhythmias. t Although not labeled for use in the treatment of supraventricular arrhythmias, propafenone has also been found to be effective in atrial flutter, atrial fibrillation, and re-entrant arrhythmias associated with the WolffParkinson-White syndrome.' By blocking the fast inward sodium channel, propafenone causes a reduction in upstroke velocity of phase 0 of the action potential (Vrnax ) and decreases conduction velocity in the atria, ventricles, and Purkinje fibers. Propafenone lengthens AH and HV conduction time and thereby prolongs the PR interval and QRS duration on the electrocardiogram. The drug reduces spontaneous automaticity and prolongs the Vma. duration and effective refractory period. In addition, propafenone has weak beta-adrenergic blocking (only 1/40 of the activity of propranolol) and some calcium-antagonist activity,' Propafenone is generally well tolerated but may cause both cardiovascular and noncardiovascular adverse effects. Cardiovascular adverse effects include proarrhytlunia, wors-
1992 July/August, Volume 26
Downloaded from aop.sagepub.com at CORNELL UNIV on August 8, 2016
Short Reports
ening of congestive heart failure, bundle branch block, and symptomatic bradycardias. Noncardiovascular effects include central nervous system reactions (e.g., dizziness and fatigue) as well as gastrointestinal reactions (e.g., nausea, constipation, dysgeusia [metallic tasteD. Rare cases of reversible leukopenia, rash, worsening of asthma, cholestatic hepatitis, and increased liver function tests have also been reported.' CASE REPORT A 71-year-old woman was referred to the outpatient cardiology clinic at The Hospital of the University of Pennsylvania (HUP) in August 1990 for treatment of paroxysmal atrial fibrillation. Her past medical history was significant for paroxysmal atrial fibrillation since February 1990 and node-negative left breast carcinoma status postmastectomy with no evidence of recurrence. Since February, the patient had been treated by her local physician first with quinidine and then procainamide. Treatment with each drug had resulted in successful conversion to normal sinus rhythm, but both agents were discontinued secondary to intolerable adverse effects. The patient was referred to HUP for alternative drug therapy for atrial fibrillation. The patient denied symptoms from her arrhythmia, but did complain of occasional chest pressure that would occur at rest, last only briefly, and often resolve upon walking. Medications included digoxin 0.25 mg/d, atenolol 25 mg/d, and warfarin 5 mg/d. On physical examination the patient was found to be a well-appearing elderly woman in no distress. Her BP was 138(70 mm Hg, and her P was irregular at 72 beats/min. Cardiac examination was remarkable for a normal SI' S2' no S3or S4' and a soft murmur of tricuspid regurgitation. There was a suggestion of V waves in her neck veins consistent with mild tricuspid regurgitation. Electrocardiogram showed atrial fibrillation at 73 beats/min and nonspecific ST- T wave changes consistent with digoxin therapy or inferolateral ischemia. A previous echocardiogram had revealed normal left ventricular function, dilated right atrium with mild tricuspid regurgitation, and mild multivalvular regurgitation, but without significant valvular heart disease. Results of laboratory studies included normal baseline liver function tests as described in Table I, prothrombin time of 16.8 s (normal 9.5-12.4) on warfarin therapy, serum electrolytes within normal limits, and a serum digoxin concentration of 1.5 ng/mL. At this time the patient was instructed to discontinue atenolol but continue taking digoxin. She was started on propafenone 150 mg tid. Over the course of the next month, the propafenone dose was increased to 225 mg tid and subsequently to 300 mg tid, resulting in conversion of atrial fibrillation to normal sinus rhythm. During that month the patient was also started on therapy with isosorbide dinitrate 20 mg tid following a positive exercise test that showed reversible inferior ischemia; digoxin therapy was discontinued. On a follow-up visit with her physician one month after initiating propafenone therapy, laboratory studies revealed asymptomatic elevations in liver function tests (alkaline phos-
phatase [ALK), alanine aminotransferase [ALT), aspartate aminotransferase [AST)) as described in Table I. Gamma glutamyltransferase (GGT) was not measured. Electrocardiogram demonstrated normal sinus rhythm. Because propafenone was suspected as a causative agent, the dose of propafenone was decreased to 225 mg tid. Ten days later the elevations in ALK, ALT, and AST had decreased slightly but were still above the upper limit of normal. Therapy with propafenone 225 mg tid, isosorbide dinitrate, and warfarin was continued. One month after discovering the abnormalities in liver enzymes, the patient returned to the HUP outpatient cardiology clinic. She was in atrial fibrillation with a rapid ventricular response of 120 beats/min on a regimen of propafenone 225 mg tid, isosorbide dinitrate, and warfarin. She was admitted to the hospital with plans of initiating an alternative antiarrhythmic drug and possibly performing electrical cardioversion. Results of liver function tests on admission included an ALK concentration that appeared to be decreased but still elevated above the upper limit of normal, ALT and AST concentrations within the normal range, and a GGT concentration (the first measured during propafenone therapy) that was greater than six times the upper limit of normal (Table I). Propafenone was discontinued secondary to recurrence of atrial fibrillation, persistent elevation in ALK, and elevation in GGT enzyme concentrations. Following cardiac angiography demonstrating normal coronary arteries and ventricular function, she was started on disopyramide 150 mg q6h. When a disopyramide serum concentration of 4.4 ug/ml, was reached, the patient underwent elective cardioversion that resulted in normal sinus rhythm at 82 beats/min. The patient was discharged on a regimen of disopyramide, digoxin, and warfarin. Follow-up laboratory studies two months after discontinuing propafenone found the elevation in ALK to have returned to baseline and elevation in GGT greatly decreased, being only slightly elevated above the upper limit of normal (Table I). Rechallenge with propafenone 900 mg/d was not performed because of continued success of disopyramide therapy in preventing recurrent atrial fibrillation.
The occurrence of liver abnormalities secondary to propafenone therapy is rare with a reported incidence of only 0.1 percent for cholestasis and 0.2 percent for elevated liver function tests (ALK, serum transaminases). In the foreign postmarketing experience, reported cases of liver injury appear to be secondary to hepatocellular injury, cholestasis, or a combination of the two. ' Propafenone has been reported to cause cholestatic hepatitis in two patients' and an eight-fold increase in serum transaminase concentrations in another patient with a past history of chronic persistent hepatitis.' Elevations in serum transaminase concentrations occurred after 15 days of therapy. In all three cases the serum enzyme concentrations returned to normal within four months following discontinuation of propafenone.
Table 1. Liver Function Tests"
PARAMETER
BASELINE
ALK (units/L) ALT (units/L) AST (units/L) LDH (units/L) TB (umol/L) GOT (units/L)
92 (35-125) 15 (0-40) 21 (0-36) 345 (220-385) 15.39 (0-20.52) 29 (0-40)
ONE MONTH AFfERDRUG INITIATION (P900 mg/d)
10 DAYS AFfER DOSAGE CHANGE (P 675 mg/d)
ONE MONTH AFfER DOSAGE CHANGE (P 675 mg/d)
TWO MONTHS AFfERDRUG DISCONTINUATION
512(29-227) 80 (3-35) 52 (7-38) 198 (75-256) 18.81 (0-18.81)
484 (29-227) 41 (3-35) 51 (7-38) 161 (75-256) 13.68 (0-18.81)
246 (35-125) II (0-40) 18 (0-36) 282 (220-385) 15.39 (0-20.52) 264 (0-40)
93 (35-125) 15 (0-40) 19 (0-36) 301 (220-385) 13.68 (0-20.52) 54 (0-40)
"Normal values are shown in parentheses. The tests were performed in two different laboratories. ALK =alkaline phosphatase; ALT =alanine aminotransferase; AST =aspartate aminotransferase; OOT hydrogenase; P = propafenone; TB =total bilirubin.
The Annals ofPharmacotherapy Downloaded from aop.sagepub.com at CORNELL UNIV on August 8, 2016
•
=gamma glutamyltransferase; LDH =lactate de1992 July/August, Volume 26
•
927
In our case, an asymptomatic increase from baseline in ALK, ALT, and AST enzyme concentrations was noted approximately one month after initiating propafenone therapy. An elevation in GGT was noted when first measured at approximately two months. Based on ALT and ALK elevations of greater than two times the upper limit of normal with a ratio of ALT serum activity to ALK serum activity
Arch Intern Med 1987;147:987-9. 7. Victorino RMM, Hodgson HJR. Relationship between T cell subpopulations and the mitogen responsiveness and suppressor cell function of peripheral blood mononuclear cells in normal individuals. Clin Exp lm-
munoI1980;42:571-8. 8. Larrey D, Henrion J, Heller F, Babany G, Degott C, Pessayre D, et al. Metoprolol-induced hepatitis: rechallenge and drug oxidation phenotyping. Ann Intern Med 1988;108:67-8. 9. Tanner LA, Bosco LA, Zimmerman HJ. Hepatic toxicity after acebutolol therapy. Ann Intern Med 1989;111:533-4. 10. Schwartz MS, Frank MS, Yanoff A, Morecki R. Atenolol-associated cholestasis. Am J Gastroenterol 1989;84:1084-6.
II. Clark JA, Zimmerman HJ, Tanner LA. Labetalol hepatotoxicity. Ann
Intern Med 1990;113:210-3. 12. Shearman DJC, Finlayson NDe. Drugs, toxins and the liver. In: Diseases of the gastrointestinal tract and liver. London: Churchill Livingstone, 1982:527-54. 13. Rotmensch HH, Leiser A, Dan M, Klejman A, Livni E, I\lie B, et al. Evaluation of prajrnalium-induced cholestasis by immunological tests.
Arch Intern Med 1981;141:1797-801. 14. Victorino RMM, Maria V AJ. Modifications of the lymphocyte transformation test in a case of drug-induced cholestatic hepatitis. Diagn Immunol 1985;3:177-81.
PROPAFENONE-INDUCED LIVER INJURY Sarah A. Spinler, Cheryl A. Elder, and K. Elizabeth Kindwall
OBJECTIVE: DFSIGN:
To describe propafenone-induced liver injury.
Retrospective case report.
Referred care in a large tertiary care center. Laboratory tests were performed at the auxiliary site and the tertiary care center.
SETIlNG:
PATIENT: A 71-year-old woman with atrial fibrillation developed elevations of greater than two times the upper limit of normal in alkaline phosphatase (ALK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GOT) after initiation ofpropafenone therapy.
INTERVENTIONS:
Studies included serial measurements of ALK, ALT,
AST, and GOT.
this case, the pattern demonstrated by elevations in liver enzymes may be classified as acute cholestatic liver injury. Because the reported incidence is 0.1-0.2 percent and there are no known fatalities secondary to propafenone liver injury, routine monitoring of liver function tests in all patients receiving propafenone cannot be recommended at this time. Baseline liver function tests prior to initiating propafenone therapy with follow-up laboratory studies one month later are recommended in patients with known liver dysfunction. If elevations are noted, a reduction in dose may result in lower liver enzyme concentrations, although discontinuation of therapy may be required in some cases.
Ann Pharmacother 1992;26:926-8.
The patient developed elevations of greater than two times the upper limit of normal in ALK, ALT, and AST, one month after initiating propafenone therapy. The propafenone dose was decreased from 900 to 675 mg/d and, ten days later, the ALK, AL T, and AST were decreased slightly, but still above the upper limit of normal. One month later, serum transaminases had returned to baseline, but propafenone therapy was discontinued because of recurrent atrial fibrillation, persistent elevation in ALK, and elevation in GOT. Two months after discontinuing propafenone, serum arninotransaminase and ALK concentrations had normalized and GOT had decreased and remained only slightly elevated. RFSULTS:
The occurrence of liver injury secondary to propafenone therapy is rare. Reported cases appear to be secondary to hepatocellular injury, cholestasis, or a combination of the two. In
CONCLUSIONS:
SARAH A. SPINLER, Pharm.D., is an Assistant Professor of Clinical Pharmacy, Philadelphia College of Pharmacy and Science, and an Adjunct Assistant Professor of Pharmacy in Medicine, University of Pennsylvania, Cardiovascular Section, Hospital of the University of Pennsylvania: CHERYL A. ELDER, B.S.Pharm.• is a Pharm.D. Student, Philadelphia College of Pharmacy and Science; and K. ELIZA· BETH KINDW ALL, M.D.. is an Assistant Professor of Medicine, University of Pennsylvania, Cardiovascular Section. Hospital of the University of Pennsylvania. Reprints: Sarah A. Spinier, Pharm.D .• Philadelphia College of Pharmacy and Science, 600 S. 43rd St., Philadelphia. PA 19104.
926
•
The Annals ofPharmacotherapy
•
PROPAFENONE HYDROCHLORIDE is a class IC antiarrhythmic agent indicated for the treatment of life-threatening ventricular arrhythmias. t Although not labeled for use in the treatment of supraventricular arrhythmias, propafenone has also been found to be effective in atrial flutter, atrial fibrillation, and re-entrant arrhythmias associated with the WolffParkinson-White syndrome.' By blocking the fast inward sodium channel, propafenone causes a reduction in upstroke velocity of phase 0 of the action potential (Vrnax ) and decreases conduction velocity in the atria, ventricles, and Purkinje fibers. Propafenone lengthens AH and HV conduction time and thereby prolongs the PR interval and QRS duration on the electrocardiogram. The drug reduces spontaneous automaticity and prolongs the Vma. duration and effective refractory period. In addition, propafenone has weak beta-adrenergic blocking (only 1/40 of the activity of propranolol) and some calcium-antagonist activity,' Propafenone is generally well tolerated but may cause both cardiovascular and noncardiovascular adverse effects. Cardiovascular adverse effects include proarrhytlunia, wors-
1992 July/August, Volume 26
Downloaded from aop.sagepub.com at CORNELL UNIV on August 8, 2016
Short Reports
ening of congestive heart failure, bundle branch block, and symptomatic bradycardias. Noncardiovascular effects include central nervous system reactions (e.g., dizziness and fatigue) as well as gastrointestinal reactions (e.g., nausea, constipation, dysgeusia [metallic tasteD. Rare cases of reversible leukopenia, rash, worsening of asthma, cholestatic hepatitis, and increased liver function tests have also been reported.' CASE REPORT A 71-year-old woman was referred to the outpatient cardiology clinic at The Hospital of the University of Pennsylvania (HUP) in August 1990 for treatment of paroxysmal atrial fibrillation. Her past medical history was significant for paroxysmal atrial fibrillation since February 1990 and node-negative left breast carcinoma status postmastectomy with no evidence of recurrence. Since February, the patient had been treated by her local physician first with quinidine and then procainamide. Treatment with each drug had resulted in successful conversion to normal sinus rhythm, but both agents were discontinued secondary to intolerable adverse effects. The patient was referred to HUP for alternative drug therapy for atrial fibrillation. The patient denied symptoms from her arrhythmia, but did complain of occasional chest pressure that would occur at rest, last only briefly, and often resolve upon walking. Medications included digoxin 0.25 mg/d, atenolol 25 mg/d, and warfarin 5 mg/d. On physical examination the patient was found to be a well-appearing elderly woman in no distress. Her BP was 138(70 mm Hg, and her P was irregular at 72 beats/min. Cardiac examination was remarkable for a normal SI' S2' no S3or S4' and a soft murmur of tricuspid regurgitation. There was a suggestion of V waves in her neck veins consistent with mild tricuspid regurgitation. Electrocardiogram showed atrial fibrillation at 73 beats/min and nonspecific ST- T wave changes consistent with digoxin therapy or inferolateral ischemia. A previous echocardiogram had revealed normal left ventricular function, dilated right atrium with mild tricuspid regurgitation, and mild multivalvular regurgitation, but without significant valvular heart disease. Results of laboratory studies included normal baseline liver function tests as described in Table I, prothrombin time of 16.8 s (normal 9.5-12.4) on warfarin therapy, serum electrolytes within normal limits, and a serum digoxin concentration of 1.5 ng/mL. At this time the patient was instructed to discontinue atenolol but continue taking digoxin. She was started on propafenone 150 mg tid. Over the course of the next month, the propafenone dose was increased to 225 mg tid and subsequently to 300 mg tid, resulting in conversion of atrial fibrillation to normal sinus rhythm. During that month the patient was also started on therapy with isosorbide dinitrate 20 mg tid following a positive exercise test that showed reversible inferior ischemia; digoxin therapy was discontinued. On a follow-up visit with her physician one month after initiating propafenone therapy, laboratory studies revealed asymptomatic elevations in liver function tests (alkaline phos-
phatase [ALK), alanine aminotransferase [ALT), aspartate aminotransferase [AST)) as described in Table I. Gamma glutamyltransferase (GGT) was not measured. Electrocardiogram demonstrated normal sinus rhythm. Because propafenone was suspected as a causative agent, the dose of propafenone was decreased to 225 mg tid. Ten days later the elevations in ALK, ALT, and AST had decreased slightly but were still above the upper limit of normal. Therapy with propafenone 225 mg tid, isosorbide dinitrate, and warfarin was continued. One month after discovering the abnormalities in liver enzymes, the patient returned to the HUP outpatient cardiology clinic. She was in atrial fibrillation with a rapid ventricular response of 120 beats/min on a regimen of propafenone 225 mg tid, isosorbide dinitrate, and warfarin. She was admitted to the hospital with plans of initiating an alternative antiarrhythmic drug and possibly performing electrical cardioversion. Results of liver function tests on admission included an ALK concentration that appeared to be decreased but still elevated above the upper limit of normal, ALT and AST concentrations within the normal range, and a GGT concentration (the first measured during propafenone therapy) that was greater than six times the upper limit of normal (Table I). Propafenone was discontinued secondary to recurrence of atrial fibrillation, persistent elevation in ALK, and elevation in GGT enzyme concentrations. Following cardiac angiography demonstrating normal coronary arteries and ventricular function, she was started on disopyramide 150 mg q6h. When a disopyramide serum concentration of 4.4 ug/ml, was reached, the patient underwent elective cardioversion that resulted in normal sinus rhythm at 82 beats/min. The patient was discharged on a regimen of disopyramide, digoxin, and warfarin. Follow-up laboratory studies two months after discontinuing propafenone found the elevation in ALK to have returned to baseline and elevation in GGT greatly decreased, being only slightly elevated above the upper limit of normal (Table I). Rechallenge with propafenone 900 mg/d was not performed because of continued success of disopyramide therapy in preventing recurrent atrial fibrillation.
The occurrence of liver abnormalities secondary to propafenone therapy is rare with a reported incidence of only 0.1 percent for cholestasis and 0.2 percent for elevated liver function tests (ALK, serum transaminases). In the foreign postmarketing experience, reported cases of liver injury appear to be secondary to hepatocellular injury, cholestasis, or a combination of the two. ' Propafenone has been reported to cause cholestatic hepatitis in two patients' and an eight-fold increase in serum transaminase concentrations in another patient with a past history of chronic persistent hepatitis.' Elevations in serum transaminase concentrations occurred after 15 days of therapy. In all three cases the serum enzyme concentrations returned to normal within four months following discontinuation of propafenone.
Table 1. Liver Function Tests"
PARAMETER
BASELINE
ALK (units/L) ALT (units/L) AST (units/L) LDH (units/L) TB (umol/L) GOT (units/L)
92 (35-125) 15 (0-40) 21 (0-36) 345 (220-385) 15.39 (0-20.52) 29 (0-40)
ONE MONTH AFfERDRUG INITIATION (P900 mg/d)
10 DAYS AFfER DOSAGE CHANGE (P 675 mg/d)
ONE MONTH AFfER DOSAGE CHANGE (P 675 mg/d)
TWO MONTHS AFfERDRUG DISCONTINUATION
512(29-227) 80 (3-35) 52 (7-38) 198 (75-256) 18.81 (0-18.81)
484 (29-227) 41 (3-35) 51 (7-38) 161 (75-256) 13.68 (0-18.81)
246 (35-125) II (0-40) 18 (0-36) 282 (220-385) 15.39 (0-20.52) 264 (0-40)
93 (35-125) 15 (0-40) 19 (0-36) 301 (220-385) 13.68 (0-20.52) 54 (0-40)
"Normal values are shown in parentheses. The tests were performed in two different laboratories. ALK =alkaline phosphatase; ALT =alanine aminotransferase; AST =aspartate aminotransferase; OOT hydrogenase; P = propafenone; TB =total bilirubin.
The Annals ofPharmacotherapy Downloaded from aop.sagepub.com at CORNELL UNIV on August 8, 2016
•
=gamma glutamyltransferase; LDH =lactate de1992 July/August, Volume 26
•
927
In our case, an asymptomatic increase from baseline in ALK, ALT, and AST enzyme concentrations was noted approximately one month after initiating propafenone therapy. An elevation in GGT was noted when first measured at approximately two months. Based on ALT and ALK elevations of greater than two times the upper limit of normal with a ratio of ALT serum activity to ALK serum activity
