Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

PURPOSE: Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. METHODS: Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. RESULTS: Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). CONCLUSIONS: Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

Medication absorption considerations in patients with postpyloric enteral feeding tubes.

PURPOSE: The gastrointestinal absorption sites of medications administered via postpyloric enteral feeding tubes were examined. SUMMARY: Many issues must be considered when administering medications via the postpyloric route, including interactions with enteral feeds, additional toxicities, and the concern of whether the medication will be absorbed. Despite the potential clinical significance of this information, data regarding the gastrointestinal site of absorption for most medications are lacking. Gastrointestinal absorption sites for all drugs for which requests for information on absorption sites were received at our institution since 2008 (n = 124) were evaluated by reviewing the package insert, consulting tertiary references, conducting primary literature searches, or contacting the drug manufacturer. Seventy (56.5%) of the 124 drugs reviewed had information available regarding the site of absorption. Just 2 drugs required acid for absorption and thus should be administered only through the stomach, while 2 other drugs were found to bind extensively to tubing and should not be administered in this manner. For 3 drugs, increased absorption may occur when they are administered directly into the small bowel. Seven medications had decreased absorption when administered directly to the small bowel, and 10 drugs were clearly not absorbed when administered through either the duodenal or the jejunal route. CONCLUSION: The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site.

Safety of epoprostenol and treprostinil in children less than 12 months of age.

There is a paucity of data on infant intravenous prostacyclin use, the gold standard for therapy for severe pulmonary hypertension (PH). This review aimed to evaluate the safety, tolerability, and outcomes of infant prostacyclin use. A retrospective observational study was performed in a large pediatric hospital with a dedicated pediatric PH program. Subject medical records, bedside flow sheets, and progress notes were reviewed to identify use of intravenous epoprostenol or treprostinil within the first year of life. The indication for prostacyclin use was recalcitrant hemodynamic compromise associated with PH, identified as either idiopathic PH, persistent PH of the newborn, PH associated with congenital diaphragmatic hernia, congenital heart disease, bronchiolitis, or chronic lung disease. Prostacyclin-related adverse events included 7 episodes of hypotension, 6 episodes of perceived pain, 2 episodes of cyanosis, and 1 episode of feeding intolerance. Prostacyclin was stopped only for cyanotic episodes associated with use in severe chronic lung disease. Two hemorrhagic events occurred during extracorporeal membrane oxygenation, which were unlikely to be prostacyclin related. Outcomes included 21 deaths unrelated to prostacyclin, 1 lung transplant, 6 PH resolutions, 8 transitions to oral PH medications, and 1 continuation of treprostinil. In conclusion, efficacy could not be evaluated in this study because of the loss of equipoise for neonatal prostacyclin use. Prostacyclin use was well tolerated in neonatal diseases associated with PH, but dose titration was limited by hypotension and hypoxemia.