A case of melphalan sustained accumulation in an 80-year old patient

Int J Clin Pharm. 2015 Dec;37(6):984-7. doi: 10.1007/s11096-015-0197-x. Epub 2015 Sep 22.

Abstract

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Keywords: Acute kidney injury; Drug interactions; Melphalan; Multiple myeloma; Pancytopenia; Trimethoprim–sulfamethoxazole combination.

Publication types

  • Case Reports

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / therapy
  • Aged, 80 and over
  • Anti-Infective Agents / adverse effects
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Critical Care
  • Drug Interactions
  • Fatal Outcome
  • Female
  • Humans
  • Kidney Failure, Chronic / complications
  • Melphalan / adverse effects*
  • Melphalan / pharmacokinetics
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy
  • Pneumonia, Pneumocystis / complications
  • Pneumonia, Pneumocystis / drug therapy
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents, Alkylating
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Melphalan