Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin®)-induced intra-hepatic cholestasis

Katsinelos, Panagiotis; Vasiliadis, Themistoklis; Xiarchos, Panagiotis; Patakiouta, Frideriki; Christodoulou, Kiriakos; Pilpilidis, Ioannis; Eugenidis, Nikolaos

doi:10.1097/00042737-200012030-00017

Cited by 41 publications

(21 citation statements)

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“…Beneficial effects in DILI, as well as in total parenteral nutrition-induced cholestasis have been reported [16]. The use of UDCA in antibiotic-induced or anabolic steroid-associated cholestatic DILI [17,18,19,20,21,22] has also been documented.…”

Section: Introductionmentioning

confidence: 99%

Steroid and Ursodesoxycholic Acid Combination Therapy in Severe Drug-Induced Liver Injury

et al. 2011

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Background: Drug-induced liver injury (DILI) is the leading cause of acute severe liver disease in Western countries. Treatment strategies for DILI are still not well defined. Aim: We studied the safety and outcomes of steroid/ursodesoxycholic acid (UDCA) combination therapy in DILI patients. Patients, Materials and Methods: 15 consecutive patients with severe DILI were analyzed for clinical, biochemical and histological data. Nine patients were treated with a steroid step-down therapy with reduction of the daily dose over several weeks; 6 patients received a steroid pulse therapy for 3 days. UDCA was administered for several weeks in both groups. Results: Patients without histological signs of preexistent liver damage (n = 10) showed the most favorable clinical course. Bilirubin and serum transaminases dropped to <50% of peak values within 2 weeks, and normalized within 4–8 weeks. In contrast, patients with positive autoimmune antibodies (anti-nuclear antibodies and/or soluble liver antigen) and/or histological features of chronic hepatitis (n = 3) exhibited a slower reduction in bilirubin and serum transaminase levels. These patients were given immunosuppressants (steroids, azathioprine) for a further 6 months. Conclusion: Treatment of severe DILI with corticosteroids (both pulse and step-down therapy) and UDCA appears to be safe, and leads to a more rapid reduction in bilirubin and transaminases after DILI.

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Section: Introductionmentioning

confidence: 99%

Steroid and Ursodesoxycholic Acid Combination Therapy in Severe Drug-Induced Liver Injury

et al. 2011

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“…Ursodeoxycholic acid can be useful in the treatment of prolonged cholestasis associated with amoxicillinclavulanate [68][69][70].…”

Section: Hepatotoxicity Related To Main Antibiotic Groups A) Penicillinsmentioning

confidence: 99%

Antibiotic-Induced Liver Toxicity: Mechanisms, Clinical Features and Causality Assessment

Robles

Toscano²,

Cotta³

et al. 2010

CDS

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Antibiotics are the therapeutic agents most often associated with hepatotoxicity. However, this is mainly due to the widespread prescription of these drugs. The relative risk of antibiotic-related hepatotoxicity is low. Causality assessment of suspected drug-induced liver injury (DILI) related to antibiotics can be difficult, particularly because some cases occur long after the drug has been stopped. Among the penicillins, amoxicillin clavulanate is the most associated with hepatotoxicity and is the most frequent cause of DILI-related hospitalisations. Flucloxacillin ranks as the second highest cause of DILI in many countries. The severity of antibiotic-induced DILI varies widely, with the hepatitis-like (hepatocellular) damage tending to be more severe that than cholestatic/mixed type. The pattern is strongly influenced by age. Recently telithromycin (a new generation macrolide) has been linked with DILI, with a typical pattern, which includes abrupt commencement of fever, abdominal pain, jaundice and, in some cases, ascites. Antibiotic-induced DILI appears, in most instances, to be idiosyncratic. Genetic-association studies have recently identified genotypes related to flucloxacillin and possibly to amoxicillin-clavulanate hepatotoxicity.

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“…Prednisone (1 mg/kg/day) and ursodeoxycholic acid (13 mg/kg/day) [8] were then prescribed (day 41 from cessation of therapy with amoxicillin-clavulanate). This treatment was promptly followed by an improvement in the clinical status of the patient and in the laboratory test results (in 5 days, total serum bilirubin levels descended from 50.75 to 9.76 mg/dL, Table 1).…”

Section: Case Reportmentioning

confidence: 99%

Corticosteroid Therapy in a Case of Severe Cholestasic Hepatitis Associated with Amoxicillin–Clavulanate

Herrero‐Herrero

García-Aparicio

2010

J. Med. Toxicol.

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Amoxicillin-clavulanate is the most common drug involved in drug-induced liver injury and the single most frequently prescribed product leading to hospitalization for drug-induced liver disease in Spain. The liver damage most frequently associated with amoxicillinclavulanate is cholestasic type. The latency period between first intake and onset of symptoms is 3-4 weeks on average. A 76-year-old man developed fever, pruritus, and jaundice 3 weeks after having completed treatment with amoxicillin-clavulanate. Liver function tests showed cholestasic hepatitis (up to 50.75 mg/dL of total serum bilirubin level). The ultrasound-guided liver biopsy revealed severe canalicular cholestasis and portal and lobular eosinophilic infiltrates. Prednisone and ursodeoxycholic acid therapy were then prescribed. The patient became symptom-free with normal liver function tests. Amoxicillin-clavulanate can cause hepatocellular, cholestasic, or mixed liver injury. The presence of eosinophilic infiltrates in the liver biopsy and the clinical signs of hypersensitivity in some of the cholestasic cases suggest a pathophysiological immunoallergic mechanism. For this reason, corticosteroid treatment should be considered for patients with severe cholestasic liver injury.

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Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin®)-induced intra-hepatic cholestasis

Cited by 41 publications

References 0 publications

Steroid and Ursodesoxycholic Acid Combination Therapy in Severe Drug-Induced Liver Injury

Steroid and Ursodesoxycholic Acid Combination Therapy in Severe Drug-Induced Liver Injury

Antibiotic-Induced Liver Toxicity: Mechanisms, Clinical Features and Causality Assessment

Corticosteroid Therapy in a Case of Severe Cholestasic Hepatitis Associated with Amoxicillin–Clavulanate

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