ZOLEDRONIC ACID: A MISCHIEVOUS SUSPECT FOR LIVER INJURY

  • Rupam Gill Department of Pharmacology, Kasturba Medical College, Manipal University, Manipal, Karnataka - 576104
  • Balaji O. Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.
  • Meena K. Kumari Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.
  • Amberkar Mohan Babu V. Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.
  • Karthik S. Udupa Department of Medical Oncology, Kasturba Hospital, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka - 576104, India.

Abstract

ABSTRACT
A 47-year-old male diagnosed as adenocarcinoma of the lung and received 8 cycles of chemotherapy comprising intravenous administration of
cisplatin 125 mg, pemetrexed 850 mg along with zoledronic acid 4 mg. After the completion of the 8
cycle, the liver enzymes were found to be
markedly elevated, evincing zoledronic acid as the cause for hepatotoxicity. The case details were taken from the patient’s medical record along with
the biochemical test reports and radiographic images. The causal association was confirmed using Naranjo’s algorithm and Roussel Uclaf Causality
Assessment Method (RUCAM). After the uneventful chemotherapy, patient’s liver function tests (LFT) were abnormal. There was an elevation in the
aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and direct bilirubin. The causal relationship was established using Naranjo’s
algorithm (score-6) and RUCAM (score-5), displayed a “probable†and “possible†association. Hartwig’s severity scale and Thornton’s preventability
scale displayed the adverse drug reaction to being moderately severe and not preventable, respectively. The zoledronic acid was stopped and never
readministered. The LFTs assumed normal after a span of 2 months. The mechanism underlying hepatotoxicity due to zoledronic acid remains elusive.
Zoledronic acid can induce acute phase response mediated by active production of interleukin-6, tumor necrosis factor alpha, and pro-inflammatory
cytokines from the T-cells and macrophages. Vigilant monitoring along with timely assessment and management can prevent the occurrence of
irreversible liver damage. Henceforth, we would like to report the rare incidence of drug induced hepatic damage due to zoledronic acid. Henceforth,
we would like to report the rare incidence of drug induced hepatic damage due to zoledronic acid.
Keywords: Bisphosphonate, Dechallenge, Hepatotoxicity, Rechallenge.
th

Author Biographies

Rupam Gill, Department of Pharmacology, Kasturba Medical College, Manipal University, Manipal, Karnataka - 576104

Tutor,

Department of Pharmacology, Kasturba Medical College, Manipal.

Balaji O., Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.

Tutor, 

Department of Pharmacology, Kasturba Medical College, Manipal.

Meena K. Kumari, Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.

Associate Professor,

Department of Pharmacology, Kasturba Medical College, Manipal.

Amberkar Mohan Babu V., Department of Pharmacology, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka – 576104, India.

Associate Professor,

Department of Pharmacology, Kasturba Medical College, Manipal.

Karthik S. Udupa, Department of Medical Oncology, Kasturba Hospital, Kasturba Medical College, Manipal Campus, Manipal University, Karnataka - 576104, India.

Assistant Professor,

Department of Medical Oncology, Kasturba Hospital, Kasturba Medical College, Manipal.

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How to Cite
Gill, R., B. O., M. K. Kumari, A. M. B. V., and K. S. Udupa. “ZOLEDRONIC ACID: A MISCHIEVOUS SUSPECT FOR LIVER INJURY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 8, Oct. 2016, pp. 3-6, doi:10.22159/ajpcr.2016.v9s2.13412.
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