Relationship of ganciclovir therapeutic drug monitoring with clinical efficacy and patient safety

Brianne M. Ritchie, Jason N. Barreto, Erin F. Barreto, Stacy A. Crow, Ross A. Dierkhising, Paul J. Jannetto, Pritish K. Tosh, Raymund R Razonable

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P 0.20 and P 0.20, respectively) or peak concentrations (P 0.14 and P 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P 0.48 and P 0.69), neutropenia (P 0.59 and P 0.69), thrombocytopenia (P 0.29 and P 0.37), anemia (P 0.51 and P 0.35), nephrotoxicity (P 0.41 and P 0.57), and neurotoxicity (P 0.22 and P 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.

Original languageEnglish (US)
Article numbere01855-18
JournalAntimicrobial Agents and Chemotherapy
DOIs
StatePublished - Mar 1 2019

Fingerprint

Ganciclovir
Drug Monitoring
Patient Safety
Viral Load
Cytomegalovirus
Cytomegalovirus Infections
Safety
Viremia
Leukopenia
Neutropenia
Thrombocytopenia
Anemia
Pharmacokinetics

Keywords

  • Antiviral therapy
  • Ganciclovir
  • Therapeutic drug monitoring
  • Viral infections

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Relationship of ganciclovir therapeutic drug monitoring with clinical efficacy and patient safety. / Ritchie, Brianne M.; Barreto, Jason N.; Barreto, Erin F.; Crow, Stacy A.; Dierkhising, Ross A.; Jannetto, Paul J.; Tosh, Pritish K.; Razonable, Raymund R.

In: Antimicrobial Agents and Chemotherapy, 01.03.2019.

Research output: Contribution to journalArticle

Ritchie, Brianne M. ; Barreto, Jason N. ; Barreto, Erin F. ; Crow, Stacy A. ; Dierkhising, Ross A. ; Jannetto, Paul J. ; Tosh, Pritish K. ; Razonable, Raymund R. / Relationship of ganciclovir therapeutic drug monitoring with clinical efficacy and patient safety. In: Antimicrobial Agents and Chemotherapy. 2019.
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abstract = "The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4{\%}) with improvement in symptomatology (70.7{\%}) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P 0.20 and P 0.20, respectively) or peak concentrations (P 0.14 and P 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P 0.48 and P 0.69), neutropenia (P 0.59 and P 0.69), thrombocytopenia (P 0.29 and P 0.37), anemia (P 0.51 and P 0.35), nephrotoxicity (P 0.41 and P 0.57), and neurotoxicity (P 0.22 and P 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.",
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AU - Dierkhising, Ross A.

AU - Jannetto, Paul J.

AU - Tosh, Pritish K.

AU - Razonable, Raymund R

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AB - The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P 0.20 and P 0.20, respectively) or peak concentrations (P 0.14 and P 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P 0.48 and P 0.69), neutropenia (P 0.59 and P 0.69), thrombocytopenia (P 0.29 and P 0.37), anemia (P 0.51 and P 0.35), nephrotoxicity (P 0.41 and P 0.57), and neurotoxicity (P 0.22 and P 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.

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