Description of Adverse Drug Events Associated with High-Dose Undiluted Etoposide (VP-16) Among Hematopoietic Stem Cell Transplant Recipients

Background:

Etoposide is an important drug in the conditioning regimen for hematopoietic stem cell transplant (HSCT). The administration of etoposide in this patient care setting presents a challenge due to limited aqueous solubility. As a result of the high doses utilized in myeloablative regimens, administration is accompanied by large volumes of intravenous fluids which increase the risk for volume overload, cardiac dysfunction, and electrolyte abnormalities. There are published reports that describe unchanged pharmacokinetic parameters between diluted and undiluted drug, as well as data describing the safe use of undiluted drug in the transplant population.

 

Methods:

We report our experience with eleven patients who received undiluted etoposide (20 mg/mL) over 4 hours through a central line in preparation for HSCT. All patients received an antihistamine and corticosteroid as premedication, as well as another dose of each and acetaminophen when half of the volume had infused. The etoposide was infused through DEHP-free tubing into a dedicated lumen. Vital signs were monitored at baseline, regularly throughout the infusion, and after the infusion was complete. 

 

Results:

Between April 2 and June 15, 2012, eleven patients received undiluted etoposide at a dose of 60 mg/kg. The most common adverse events documented were gastrointestinal toxicities. All patients reported nausea and most cases were accompanied by emesis, requiring an average of 4.4 antiemetic doses for treatment of breakthrough nausea/vomiting. Hypotension was documented in nine patients, with an average drop in systolic blood pressure of 35 mm Hg (range: 15-46 mm Hg) occurring 6.6 hours (range: 1.7-18.8 hours) after the start of etoposide infusion. Nine patients required fluid resuscitation with an average of 1400 mL (range: 500 mL-3500 mL) of normal saline.

 

Conclusion:

Despite published reports of successful administration of undiluted etoposide in myeloablative conditioning regimens, we report numerous adverse events in our patient population. All patients treated at our institution with undiluted etoposide as part of the conditioning regimen experienced side effects related to the drug. The benefits of administering undiluted etoposide should be carefully weighed against the possibility of related toxicities.