Drug-Drug Interactions, Safety, and Pharmacokinetics of EGFR Tyrosine Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Inhibitors of the epidermal growth factor receptor (EGFR) are important treatment options for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Erlotinib, gefitinib, afatinib, and osimertinib are approved for use in NSCLC patients, and several other agents are in clinical development. The objectives of this article are to review the pharmacokinetic and known drug interaction data for EGFR tyrosine kinase inhibitors (TKIs) available for use in NSCLC patients, as well as adverse events (AEs) commonly observed with EGFR-TKI treatment, and to discuss relevant management strategies. The importance of this information for patient care is explored from the perspective of advanced practitioners. Pharmacokinetic, drug-interaction, and safety data are included for EGFR inhibitors approved for NSCLC (erlotinib, gefitinib, afatinib, and osimertinib). Relevant dose modifications and AE management strategies are also reviewed. The interdisciplinary health-care team plays an essential role in patient education, care planning, and medication administration. As such, it is essential that advanced practitioners understand the safety profiles and the potential for drug interactions with EGFR TKIs to ensure patients achieve the maximum benefit from these agents.

Impact of shortages of injectable oncology drugs on patient care.

PURPOSE: Results of a survey regarding shortages of injectable oncology drugs in U.S. hospitals and health systems are presented. METHODS: An online survey was sent to all members of the American Society of Health-System Pharmacists self-identified as directors of pharmacy. Survey participants provided information on the extent to which their facilities were affected by oncology drug shortages, strategies for responding to shortages, and the effects of shortages on costs, patient safety, and outcomes. RESULTS: Ninety-eight percent of the 358 survey respondents reported at least one drug shortage during the previous 12 months, with 70% reporting instances of an inadequate supply to treat patients and 63% reporting that their facility had completely run out of at least one injectable oncology drug. Sixty-two percent of respondents reported using alternative drug regimens due to shortages; 46% reported drug dosage changes, 43% reported treatment delays, and 21% reported patient referrals to or from other facilities as a result of shortages. Survey respondents indicated the use of various strategies to manage oncology drug shortages (e.g., increasing inventories of certain drugs, identifying alternatives and substitution protocols, altered purchasing practices), all of which have led to cost increases. Twenty-five percent of respondents reported safety events resulting from oncology drug shortages. Only 40% of respondents agreed that currently available information is useful in mitigating the effects of shortages. CONCLUSION: Shortages of injectable oncology drugs appear to be widespread and to be having a significant impact on patient care. Currently available information about shortages does not meet administrative or clinical needs.

A retrospective analysis of the effect of patient-specific factors on voriconazole concentrations in oncology patients.

OBJECTIVE: To identify patient-specific factors significantly associated with voriconazole exposure. DESIGN SETTING, AND PARTICIPANTS: Retrospective, single center at an academic medical center. Consecutive, adult oncology inpatients who received voriconazole by mouth and had at least one voriconazole level over a 14-month period. Voriconazole was ordered for 292 patients during the study period, a level was obtained in 41 patients. Nine patients were excluded; the study population was comprised of 32 patients. METHODS AND RESULTS: Univariate and multivariable regression analyses were utilized to predict the patient-specific factors significantly associated with level. A total of 36 levels meeting inclusion/exclusion criteria were performed in 32 patients. Sixty percent of levels (22/36) were between 1 and 5.5 µg/mL. Data were available to calculate a Child Pugh score for 66% (21/32) of patients. Using multivariable linear regression, three covariates were found to be statistically significant: age, international normalized ratio (INR), and alkaline phosphatase (ALP). Three outliers were notable in the ALP category, when removing the three individuals from the model, only an increasing INR remains significantly associated with increasing voriconazole level (p = 0.0093). No correlation was found with trough level and Child Pugh score. CONCLUSIONS: Sixty percent of voriconazole trough levels were between 1 and 5.5 µg/mL (range 0.1-7.4 µg/mL), only increasing INR was significantly associated with rising voriconazole level. Increasing Child Pugh score was not associated with increasing level. More investigation is warranted into the usefulness of the Child Pugh score for guidance of dose modifications in non-cirrhotic patients with acute hepatic injury.