Deprecated function: Return type of DatabaseStatementBase::execute($args = [], $options = []) should either be compatible with PDOStatement::execute(?array $params = null): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2246 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Deprecated function: Return type of DatabaseStatementEmpty::current() should either be compatible with Iterator::current(): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2348 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Deprecated function: Return type of DatabaseStatementEmpty::next() should either be compatible with Iterator::next(): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2348 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Deprecated function: Return type of DatabaseStatementEmpty::key() should either be compatible with Iterator::key(): mixed, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2348 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Deprecated function: Return type of DatabaseStatementEmpty::valid() should either be compatible with Iterator::valid(): bool, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2348 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Deprecated function: Return type of DatabaseStatementEmpty::rewind() should either be compatible with Iterator::rewind(): void, or the #[\ReturnTypeWillChange] attribute should be used to temporarily suppress the notice in require_once() (line 2348 of /var/www/webmd/apps/mdedge/htdocs/includes/database/database.inc).
Original Research
Paclitaxel Drug-Drug Interactions in the Military Health System
aWalter Reed National Military Medical Center, Bethesda, Maryland
bTripler Army Medical Center, Honolulu, Hawaii
cJohn P. Murtha Cancer Center, Bethesda, Maryland
dJoint Pathology Center, Silver Spring, Maryland
Author disclosures
The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the official position or policy of the Defense Health Agency, US Department of Defense, the US Government, or any of its agencies. This article maydiscuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Ethics and consent
The study protocol was approved by the Walter ReedNational Military Medical Center Institutional Review Board and complied with the Health Insurance Portability and Accountability Act as an exempt protocol.
The mean (SD) number of diagnoses was 51 (31) for the completed and 55 (28) for the discontinued treatment groups (Figure). Among 639 patients who received paclitaxel, the top 5 diagnoses were administrative, including encounters for other administrative examinations; antineoplastic chemotherapy; administrative examination for unspecified; other specified counseling; and adjustment and management of vascular access device. The database does not differentiate between administrative and clinically significant diagnoses.
MHS data analysts provided data for 336 of 687 submitted patients who were prescribed paclitaxel; 46 patients had no PDTS data, and 305 patients had PDTS data without paclitaxel, Taxol, or Abraxane dispensed. Medications that were filled outside the chemotherapy period were removed by evaluating the dispensed date and day of supply. Among these 336 patients, 151 completed the treatment and 185 discontinued, with 14 patients experiencing documented AEs. Patients in the completed treatment group filled 9 to 56 prescriptions while patients in the discontinued treatment group filled 6 to 70 prescriptions.Patients in the discontinued group filled more prescriptions than those who completed treatment: 793 vs 591, respectively (P = .34).
The mean (SD) number of filled prescription drugs was 24 (9) for the completed and 34 (12) for the discontinued treatment group. The 5 most filled prescriptions with paclitaxel from 336 patients with PDTS data were dexamethasone (324 prescriptions with 14 recorded AEs), diphenhydramine (296 prescriptions with 12 recorded AEs), ondansetron (277 prescriptions with 11 recorded AEs), prochlorperazine (265 prescriptions with 12 recorded AEs), and sodium chloride (232 prescriptions with 11 recorded AEs).
DISCUSSION
As a retrospective review, this study is more limited in the strength of its conclusions when compared to randomized control trials. The DoD Cancer Registry Program only contains information about cancer types, stages, treatment regimens, and physicians’ notes. Therefore, noncancer drugs are based solely on the PDTS database. In most cases, physicians' notes on AEs were not detailed. There was no distinction between initial vs later lines of therapy and dosage reductions. The change in status or appearance of a new medical condition did not indicate whether paclitaxel caused the changes to develop or directly worsen a pre-existing condition. The PDTS records prescriptions filled, but that may not reflect patients taking prescriptions.
Paclitaxel
Paclitaxel has a long list of both approved and off-label uses in malignancies as a primary agent and in conjunction with other drugs. The FDA prescribing information for Taxol and Abraxane was last updated in April 2011 and September 2020, respectively.20,21 The National Institutes of Health National Library of Medicine has the current update for paclitaxel on July 2023.19,22 Thus, the prescribed information for paclitaxel referenced in the database may not always be up to date. The combinations of paclitaxel with bevacizumab, carboplatin, or carboplatin and pembrolizumab were not in the Taxol prescribing information. Likewise, a combination of nab-paclitaxel with atezolizumab or carboplatin and pembrolizumab is missing in the Abraxane prescribing information.22-27
The generic name is not the same as a generic drug, which may have slight differences from the brand name product.71 The generic drug versions of Taxol and Abraxane have been approved by the FDA as paclitaxel injectable and paclitaxel-protein bound, respectively. There was a global shortage of nab-paclitaxel from October 2021 to June 2022 because of a manufacturing problem.72 During this shortage, data showed similar comments from physician documents that treatment switched to Taxol due to the Abraxane shortage.
Of 336 patients in the PDTS database with dispensed paclitaxel prescriptions, 276 received paclitaxel (year dispensed, 2013-2022), 27 received Abraxane (year dispensed, 2013-2022), 47 received Taxol (year dispensed, 2004-2015), 8 received both Abraxane and paclitaxel, and 6 received both Taxol and paclitaxel. Based on this information, it appears that the distinction between the drugs was not made in the PDTS until after 2015, 10 years after Abraxane received FDA approval. Abraxane was prescribed in the MHS in 2013, 8 years after FDA approval. There were a few comparison studies of Abraxane and Taxol.73-76
Safety and effectiveness in pediatric patients have not been established for paclitaxel. According to the DoD Cancer Registry Program, the youngest patient was aged 2 months. In 2021, this patient was diagnosed with corpus uteri and treated with carboplatin and Taxol in course 1; in course 2, the patient reacted to Taxol; in course 3, Taxol was replaced with Abraxane; in courses 4 to 7, the patient was treated with carboplatin only.
