Nephrol Dial Transplant (1999) 14: 2776-2777
© 1999 European Renal Association-European Dialysis and Transplant Association
Letters
Dihydropyridine calcium channel blockers: a rare and reversible cause of hepatotoxicity with cholestasis in a CAPD patient
Nephrology Unit, Hospital of Martina Franca 1 Department of Surgery, Military Hospital of Taranto, Italy
Sir,
A 76-year-old diabetic man was admitted to our unit in May 1998, to start peritoneal dialysis treatment because of severe chronic renal failure. At this time the drug regimen consisted of furosemide, nifedipine in the extended release tablet dosage form (Adalat Crono® 60 mg, Bayer, Italy) for at least 3 years, and insulin. Liver function tests were normal, search for hepatotropic viruses was negative and abdominal ultrasonography showed normal liver and gallbladder.
In September 1998, liver function tests began to deteriorate (Table 1
). Subsequently, overt jaundice occurred. Viral examinations continued to be negative, as was abdominal ultrasonography. On January 11, 1999 nifedipine was withdrawn. Thereafter, liver function tests normalized rapidly (Table 1). At the end of March 1999, another dihydropyridine calcium channel blocker, amlodipine (Norvasc® 10 mg, Pfizer, Italy), was prescribed to this patient. To the best of our knowledge, hepatotoxicity with cholestasis had never been reported as a side effect of amlodipine. In April 1999, liver function tests began to deteriorate again (Table 2). Subsequently, overt jaundice occurred. On May 7, 1999 amlodipine was withdrawn. Thereafter, liver function tests normalized rapidly (Table 2). Search for serum markers of hepatotropic viruses was again negative.
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The slow-release formulation of nifedipine was introduced in the US in 1989 and reached a plateau of 7000000 new prescriptions per year in the years 1992–1994 [1]. Amlodipine was introduced in the US in 1992 and reached a plateau of 2000000 new prescriptions per year in 1994 [1]. We document here a very rarely reported side effect of nifedipine, namely hepatotoxicity with cholestasis [2–6]. Furthermore, we document for the first time the same side effect also for amlodipine. Thus, we hypothesize that, at least in this patient, hepatotoxicity with cholestasis is a side effect common to dihydropyridine calcium channel blockers. As in the very few other cases reported in the literature, it disappeared with drug withdrawal. The peculiarity of our case is that hepatotoxicity occurred after 3 years of uneventful continuous administration of nifedipine. Available evidence suggests that hepatic reactions to nifedipine are due to hypersensitivity [4]. We wish to alert the Nephrology community to the possible relationship between dihydropyridine calcium channel blockers and abnormal liver function.
References
- Kaplan NM, Rose BD. Major side effects and safety of calcium channel blockers. In: Rose BD, ed. Up-To-Date, Inc. Wellesley, USA: 1998: 6.2
- Rothmensch HH, Roth A, Liron M, Rubenstein A, Gefel A, Livini E. Lymphocyte sensitisation in nifedipine-induced hepatitis. Br Med J 1980; 281: 976–977
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Davidson AR. Lymphocyte sensitisation in nifedipine—induced hepatitis. Br Med J 1980; 281: 1354
[Free Full Text] - Abramson M, Littlejohn GO. Hepatic reactions to nifedipine. Med J Aust 1985; 7: 47–48
- Kiire CF, Rutherford D. Nifedipine-associated jaundice: a second case. East African Med J 1986; 63: 560–561[Web of Science][Medline]
- Sawaya GF, Robertson PA. Hepatotoxicity with the administration of nifedipine for treatment of preterm labor. Am J Obstet Gynecol 1992; 167: 512–513[Web of Science][Medline]
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