Fusidic acid induced jaundice

Haddad, M; Shabat, Sheerli Kruger Ben; Koren, Amir; Stelman, E; Zelikovski, A

doi:10.1007/bf02009392

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Finally, our findings also raise an intriguing possibility that the clinical cases of hyperbilirubinemia/jaundice noted with FA use (Humble et al, 1980;Kutty et al, 1987;Haddad et al, 1993) could be potentially linked to its inhibitory effects on the OATP1B1-and OATP1B3-mediated bilirubin transport into the liver. Hepatic uptake of bilirubin by OATPs constitutes the first step in the multifaceted elimination process of the heme breakdown product (Cui et al, 2001); a combination of inhibitory effects on bilirubin uptake and/or bilirubin glucuronidation in the liver has emerged as a common theme among drugs associated with clinical hyperbilirubinemia (Chiou et al, 2014).…”

Section: Downloaded Frommentioning

confidence: 97%

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Eng

Scialis

Rotter

et al. 2016

Drug Metabolism and Disposition

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Chronic treatment of methicillin-resistant Staphylococcus aureus strains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC 50 = 295 6 1.0 mM) and time-dependent (K I = 216 6 41 mM and k inact = 0.0179 6 0.001 min 21) inhibitor of CYP3A4-catalyzed midazolam-19-hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC 50 value of 157 6 1.0 mM and was devoid of breast cancer resistance protein inhibition (IC 50 > 500 mM). In contrast, FA showed potent inhibition of OATP1B1-and OATP1B3-specific rosuvastatin transport with IC 50 values of 1.59 mM and 2.47 mM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC 50 = 2.26 mM) and Oatp1b2 (IC 50 = 4.38 mM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity.

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Section: Downloaded Frommentioning

confidence: 97%

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Eng

Scialis

Rotter

et al. 2016

Drug Metabolism and Disposition

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“…[13,14] Subsequently, 10 cases of FA-associated jaundice and hyperbilirubinemia were also reported. [15–19] FA is eliminated primarily by biliary excretion of various conjugative and cytochrome P450 oxidative metabolites. [20] Wynn [21] postulated that FA may interfere with pathways involved in the transport and secretion of bile pigment.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity and hematologic complications induced by fusidic acid in a patient with hepatitis B cirrhosis

He¹,

Chen

Zhang³

et al. 2019

Medicine

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Rationale:Fusidic acid (FA) is an active agent against gram-positive bacteria such as Staphylococcus, it is generally well tolerated and the major adverse effects are mild gastrointestinal discomfort, diarrhea, and headache. However, some rare side effects such as granulocytopenia and thrombocytopenia have also been reported. Here we report a case of FA-induced hepatotoxicity and hematologic toxicity.Patient concerns:A 54-year-old woman with hepatitis B cirrhosis was referred to us because of fever, Staphylococcus aureus was identified in the twice blood culture, and intravenous FA was given (0.5 g, q8 hours). Twelve days after FA therapy, she developed nausea and jaundice. Meanwhile, complete blood cell count showed neutropenia (white blood cell count of 1360/μL, neutrophil of 619/μL) and aggravated thrombocytopenia (platelet count of 18,000/μL). Adverse drug reaction was suspected, and FA was stopped immediately, after 1 day of discontinuation of FA, nose bleeding occurred and the platelet count declined further and reached the lowest value of 4000/μL.Diagnoses:Hepatotoxicity and hematologic complications induced by FA were diagnosed.Interventions and outcomes:The FA was stopped immediately, and concentrated platelet transfusion was used. Five days after withdrawal of FA, jaundice resolved and the hematologic index returned to the level before the medication.Lessons:Hematologic adverse effect accompanying with hepatotoxicity may be induced by FA. Though the risk is rather low, it should not be overlooked.

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“…Jaundice is reversible and mainly associated with intravenous administration. Rarely reported side effects include granulocytopenia, thrombocytopenia, and venous spasm [157–159].…”

Section: Alternatives To Classically Used Drugsmentioning

confidence: 99%

New therapeutic choices for infections caused by methicillin-resistant Staphylococcus aureus

Bouza

2009

Clinical Microbiology and Infection

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Fusidic acid induced jaundice

Cited by 6 publications

References 14 publications

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Hepatotoxicity and hematologic complications induced by fusidic acid in a patient with hepatitis B cirrhosis

New therapeutic choices for infections caused by methicillin-resistant Staphylococcus aureus

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