Concomitant administration of candesartan cilexetil in patients on paclitaxel and carboplatin combination therapy increases risk of severe neutropenia

Int J Clin Pharmacol Ther. 2018 Jul;56(7):328-336. doi: 10.5414/CP203180.

Abstract

Objective: Angiotensin receptor blockers (ARBs) are often used in patients on paclitaxel (PTX) and carboplatin combination (TC) therapy to treat hypertension caused by the co-administration of bevacizumab. The aim of this retrospective study was to analyze the association between co-administration of ARBs and the development of severe neutropenia in patients on TC therapy.

Materials and methods: In this study, 211 concomitant medications were prescribed to 173 patients on TC therapy. 24 of those patients received ARBs. The incidences of neutropenia among those on various ARBs were compared.

Results: Patients on candesartan cilexetil had the highest incidence of neutropenia compared to those on other concomitant medications, including other ARBs. Of 173 patients, 6 received candesartan cilexetil during the first cycle of TC therapy, and all 6 of them developed severe neutropenia. We noted that prior to TC therapy, there were no significant differences in age, serum albumin levels, neutrophil counts, liver injury marker, and renal function between the patients on candesartan cilexetil and those on other ARBs.

Conclusion: Our data suggest that a drug-drug interaction between candesartan cilexetil and TC therapy is probable. Unlike with other ARBs, the possible increased risk for development of severe neutropenia should be taken into account when prescribing candesartan cilexetil in combination with TC therapy. .

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / adverse effects*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects*
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / adverse effects*
  • Blood Pressure / drug effects*
  • Carboplatin / adverse effects*
  • Drug Interactions
  • Female
  • Humans
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neutropenia / blood
  • Neutropenia / chemically induced*
  • Neutropenia / diagnosis
  • Neutropenia / epidemiology
  • Paclitaxel / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Tetrazoles / administration & dosage
  • Tetrazoles / adverse effects*
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • Carboplatin
  • Paclitaxel
  • candesartan cilexetil