1978
DOI: 10.1159/000198145
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Perhexiline Maleate-Induced Hepatitis

Abstract: 5 patients treated with perhexiline maleate, 200–400 mg/day for at least 6 months, exhibited evidence of hepatitis. The picture was very similar to acute alcoholic hepatitis, clinically, biologically and histologically with presence of necrosis, Mallory’s hyaline, polynuclear infiltration and to a lesser degree, steatosis. Association with peripheral neuropathy, hypoglycemia, and renal failure appears strikingly frequently. The evolution was severe since 3 patients died within 6 months, even after treatment wi… Show more

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Cited by 39 publications
(8 citation statements)
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“…[27] During long term treatment with perhexiline in the 1970s and 1980s, it became apparent that perhexiline was also associated with infrequent but serious adverse effects. [42][43][44] These included neurological adverse effects, hepatic toxicity, [45,46] renal impairment, [46] severe bodyweight loss [47] and hypoglycemia, [48,49] often occurring together in the same patient. These adverse effects appear to be due to accumulation of perhexiline associated with administration of excessive dosages or impaired drug metabolism.…”
Section: Clinical Trial Datamentioning
confidence: 99%
“…[27] During long term treatment with perhexiline in the 1970s and 1980s, it became apparent that perhexiline was also associated with infrequent but serious adverse effects. [42][43][44] These included neurological adverse effects, hepatic toxicity, [45,46] renal impairment, [46] severe bodyweight loss [47] and hypoglycemia, [48,49] often occurring together in the same patient. These adverse effects appear to be due to accumulation of perhexiline associated with administration of excessive dosages or impaired drug metabolism.…”
Section: Clinical Trial Datamentioning
confidence: 99%
“…Perhexiline is an effective antianginal drug but can cause severe toxicity, notably hepatotoxicity [1–5] and peripheral neuropathy [6–10]. Its pharmacokinetics are complex as it has a long elimination half‐life of days to weeks [11], the steady‐state plasma concentration to dose ratio varies more than a 100‐fold [12], and the systemic clearance is saturable [13].…”
Section: Introductionmentioning
confidence: 99%
“…-12 The neuropathy and the hepatic damage may not reverse when the drug is withdrawn and deaths have been recorded. [11][12][13][14][15][16][17][18] Severe adverse reactions follow the use of perhexiline in only a percentage of patients and are perhaps associated with impaired metabolism of the drug. Perhexiline is a lipophilic drug and its elimination depends on hepatic oxidation to the more polar monohydroxylated and dihydroxylated metabolites.19 Several drug oxidations in man are under single gene control and exhibit genetic polymorphism.2t21 Oxidation is regulated by two alleles, DH-rapid and extensive oxidation and DL_ slow impaired oxidation.2' Individuals homozygous for the DL allele have an impaired ability to.oxidise many drugs.…”
mentioning
confidence: 99%
“…"'12 13 18 29 30 The course of the liver patients are biopsied. Poupon et a133 for example, disease is variable; usually transaminase values studied 46 patients on maintenance perhexiline and return to normal within a month of perhexiline found hepatomegaly in 13% (6/46), raised serum withdrawal4 31 although in some patients the liver bile acid values in 57% (26/46) abnormal BSP lesion progresses despite withdrawal of the drug.1' retention in 74% (34/46) but evidence of histological The mortality in patients who develop cirrhosis is damage in all 11 patients in whom liver biopsy was high [11][12][13][14][15][16][17][18]. …”
mentioning
confidence: 99%