A case of severe toxicity during coadministration of vincristine and piperacillin: are drug transporters involved in vincristine hypersensitivity and drug-drug interactions?

J Pediatr Hematol Oncol. 2012 Nov;34(8):e341-3. doi: 10.1097/MPH.0b013e318257a4ae.

Abstract

Neurotoxicity is frequent with vincristine treatment, but severe autonomic neuropathy is rare. A decreased activity of drug transporters in the presence of an interacting drug may favor such events by increasing systemic or tissue exposure to the drug. We encountered severe autonomic neuropathy and cholestasis in a child receiving vincristine, after the introduction of piperacillin-tazobactam. A causality assessment of the adverse reaction identified the antibiotic as the most probable cause of the observation. The patient was heterozygous for several common polymorphisms of ABCC2 (multidrug-related protein-2), CYP3A5, and ABCB1 (multidrug-related protein-1, P-glycoprotein), but their role in the toxicity cannot be ascertained.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Abdominal Pain / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Asparaginase / administration & dosage
  • Autonomic Nervous System Diseases / chemically induced*
  • Autonomic Nervous System Diseases / drug therapy
  • Biological Transport
  • Child
  • Cholestasis / chemically induced*
  • Cyclophosphamide / administration & dosage
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / physiology
  • Daunorubicin / administration & dosage
  • Drug Combinations
  • Drug Interactions
  • Facial Pain / chemically induced
  • Female
  • Humans
  • Intestinal Obstruction / etiology
  • Intestinal Pseudo-Obstruction / etiology
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / physiology
  • Nalbuphine / therapeutic use
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Neuralgia / chemically induced*
  • Neuralgia / drug therapy
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / therapeutic use
  • Piperacillin / administration & dosage
  • Piperacillin / adverse effects*
  • Piperacillin / pharmacokinetics
  • Piperacillin / therapeutic use
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prednisone / administration & dosage
  • Seizures / drug therapy
  • Seizures / etiology
  • Tazobactam
  • Vincristine / administration & dosage
  • Vincristine / adverse effects*
  • Vincristine / pharmacokinetics

Substances

  • ABCB1 protein, human
  • ABCC2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Drug Combinations
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Vincristine
  • Penicillanic Acid
  • Cyclophosphamide
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Asparaginase
  • Nalbuphine
  • Tazobactam
  • Prednisone
  • Piperacillin
  • Daunorubicin