Probable fatal drug interaction between intravenous fenretinide, ceftriaxone, and acetaminophen: a case report from a New Approaches to Neuroblastoma (NANT) Phase I study

BMC Research Notes

Barry J Maurer⁶  Araz Marachelian⁷  C Patrick Reynolds⁶  Matthew M Ames⁵  Scarlett Czarnecki¹  Richard Sposto⁷  Susan Groshen²  Katherine K Matthay⁴  Julia L Glade Bender³  Judith G Villablanca⁷  Min H Kang⁶ 

[1] NANT Operations Center, Children’s Hospital Los Angeles, 4650 Sunset Blvd, 90027 Los Angeles, CA, USA;Department of Biostatistics, School of Medicine, University of Southern California, 1441 Eastlake Ave, 90089 Los Angeles, CA, USA;Department of Pediatric Hematology & Oncology, Columbia University, 161 Fort Washington Ave, 10032 New York, NY, USA;Division of Pediatric Hematology-Oncology, University of California San Francisco, 505 Parnassus Ave M647, 94143 San Francisco, CA, USA;Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 17778 East North Shore Lane, Bayview, 83803 Idaho, USA;Cancer Center and Departments of Cell Biology and Biochemistry, Pharmacology and Neuroscience, Pediatrics, and Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 9445 79430 Lubbock, TX, USA;Department of Pediatrics, University of Southern California, 4650 Sunset Blvd, 90027 Los Angeles, CA, USA

关键词: Fulminant hepatic failure;    Biliary sludge;    Drug interaction;    Acetaminophen;    Fenretinide;    Ceftriaxone;   

Others  :  1133263
DOI  :  10.1186/1756-0500-7-256

 received in 2014-03-19, accepted in 2014-04-16,  发布年份 2014

【 摘 要 】

Background

Patients with relapsed/refractory stage 4 high-risk neuroblastoma were enrolled on a phase I study (NANT2004-03) of intravenous fenretinide emulsion. Pharmacokinetic samples were collected during and after the infusion, and the levels were measured using an HPLC system. A likely case of a fatal drug interaction between fenretinide, ceftriaxone, and acetaminophen is described, including the pharmacokinetics of fenretinide, laboratory data, and post-mortem autopsy in a pediatric neuroblastoma patient treated on this study.

Case presentation

On Day 4 of a scheduled 5-day-infusion of intravenous fenretinide, the patient developed a fever, acetaminophen was started, ceftriaxone initiated for possible bacteremia, and fenretinide level doubled from 56 to 110 μM. Over the next three days, although blood cultures remained negative, the patient’s condition deteriorated rapidly. Acute liver failure was diagnosed on Day 7, and the patient expired on Day 20 of fulminant hepatic failure with associated renal, cardiac, and hemorrhagic/coagulation toxicities. Autopsy showed extensive hemorrhagic necrosis of the liver, marked bile duct proliferation, and abundant hemosiderin, consistent with cholestasis and drug toxicity.

Conclusions

After extensive review of patient data, the clinical course, and the literature, we conclude that observed hepatic toxicity was likely due to a drug interaction between fenretinide and concomitant ceftriaxone and acetaminophen. None of the other 16 patients treated on this study experienced significant hepatic toxicity. Although the prevalence of cholestasis with ceftriaxone usage is relatively high, the potential drug interaction with these concomitant medications has not been previously reported. Concomitant use of fenretinide, ceftriaxone, and acetaminophen should be avoided.

【 授权许可】

   
2014 Kang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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