Mary Petrea Cober

Intravenous Fat Emulsions Reduction for Patients with Parenteral Nutrition–Associated Liver Disease

OBJECTIVE To test the hypothesis that implementation of a marked reduction in intravenous fat will result in reversal of parenteral nutrition-associated liver disease (PNALD) in infants. STUDY DESIGN Prospective study of intravenous fat emulsion reduction in parenteral nutrition to 1 g/kg/d 2 times per week in neonates diagnosed with PNALD. Primary outcome measure was total bilirubin levels compared with gestational age, birth weight, and diagnosis-matched historical controls receiving 3 g/kg/d of intravenous lipids. RESULTS Intravenous fat emulsion reduction resulted in a significant decline in total bilirubin levels compared with controls. Comparison of growth in the 2 groups was similar. Mild essential fatty acid deficiency was detected in 8 of 31 infants and was reversed with additional days of lipid infusion. No significant adverse events were noted. CONCLUSIONS An association between intravenous lipid emulsion administration and the development of PNALD seems probable. Use of intravenous fat emulsion reduction is a potential approach to reverse PNALD in young infants. Frequent monitoring of essential fatty acid deficiency is needed with the use of this regimen.

Otitis Media: Review of the 2004 Treatment Guidelines

OBJECTIVE To review the 2004 treatment guidelines provided by the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) regarding the treatment of otitis media in pediatric patients. DATA SOURCES A MEDLINE search, restricted to English-language articles about pediatric patients, was conducted (1966–May 2005) using the key words acute otitis media (AOM), guideline, observation therapy, and vaccination. Additional references were located through review of the bibliographies of cited articles. STUDY SELECTION AND DATA EXTRACTION Studies related to the fundamental basis of the updated guidelines and articles addressing current issues related to otitis media infection were included. DATA SYNTHESIS Otitis media affects many children in the US. Concerns have been raised about the proper treatment of AOM in the face of increasing drug resistance among primary pathogens responsible for infection. Some countries have chosen to observe patients for a designated period of time prior to initiation of antibiotic therapy. The AAP and AAFP have updated the treatment guidelines for otitis media to include the option of observation therapy, recommendations for dosing of various antibiotic regimens and their place in therapy, and the importance of initial pain management. CONCLUSIONS Updated treatment guidelines for otitis media have been developed in an effort to properly treat children while decreasing current resistance rates for common organisms that cause AOM. In the future, the therapeutic outcomes of observation therapy related to both the incidence of drug resistance and the possibility of increased complications related to otitis media will need to be evaluated in the US.

Stability of Partial Doses of Omeprazole-Sodium Bicarbonate Oral Suspension

Background: Omeprazole-sodium bicarbonate powder for oral suspension has recently been marketed. The manu facturer provides no information regarding the acceptability of using partial doses and recommends that the reconstituted suspension be administered immediately after preparation. Objectives: To determine the stability of the powder for oral suspension over 45 days, evaluate the stability of a partial dose (<20 mg) following exposure to Simulated Gastric Fluid USP (SGF) over 2 hours, and determine the feasibility of administering the suspension through neonatal and pediatric nasogastric feeding tubes compared with lansoprazole. Methods: Three identical samples of omeprazole–sodium bicarbonate suspension 2 mg/mL were stored in the refrigerator (3–5°C) and assayed by high-performance liquid chromatography immediately after preparation and at 7, 15, 30, and 45 days. Stability of a 1 mg/kg dose with an estimated volume of SGF for a simulated 12.7 kg pediatric patient was determined In triplicate over 2 hours at 37°C. The ability to administer a typical dose of omeprazole suspension and lansoprazole suspension (microgranules and water compounded from lansoprazole oral disintegrating tablets) was assessed in triplicate using 3 different sizes of neonatal/pediatric nasogastric feeding tubes. Results: At least 98% of the initial concentration of omeprazole remained throughout the 45 day study period in all suspensions. The suspension maintained at least 93% of the initial concentration following exposure to SGF for 2 hours. The lansoprazole bead mixture partially clogged the 6 French feeding tube and completely clogged the 5 French feeding tube. The omeprazole-sodium bicarbonate suspension was easily administered through all 3 sizes of neonatal/pediatric feeding tubes. Conclusions: Omeprazole-sodium bicarbonate suspension 2 mg/mL prepared from 20 mg packets was stable for at least 45 days when stored at 3–5°C. A partial dose of 12.7 mg was stable following exposure to SGF for 2 hours at 37°C. This suspension can be easily administered through 5, 6, and 8 French neonatal/pediatric feeding tubes and, when taking time and ease of preparation into account, it is cost competitive with simple omeprazole suspension.

Stability of extemporaneously prepared rifaximin oral suspensions

PURPOSE The stability of extemporaneously prepared rifaximin oral suspensions was studied. METHODS An oral suspension of rifaximin 20 mg/mL was prepared by thoroughly grinding six 200-mg tablets of rifaximin in a glass mortar. Thirty milliliters of Ora-Plus and 30 mL of either Ora-Sweet or Ora-Sweet SF were mixed and added to the powder to make a final volume of 60 mL. Three identical samples of each formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and were stored at room temperature (23-25 degrees C). A 1-mL sample was withdrawn from each of the six bottles with a micropipette immediately after preparation and at 7, 15, 30, and 60 days. After further dilution to an expected concentration of 20 microg/mL with mobile phase, the samples were assayed in duplicate using stability-indicating high-performance liquid chromatography. The samples were visually examined for any color change and pH was tested on each day of analysis. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point and defined as retention of at least 90% of the initial concentration of rifaximin. RESULTS At least 99% of the initial rifaximin remained throughout the 60-day study period in both preparations. There were no detectable changes in color, odor, taste, or pH and no visible microbial growth in any sample. CONCLUSION Extemporaneously prepared suspensions of rifaximin 20 mg/mL in 1:1 mixtures of Ora-Plus with either Ora-Sweet or Ora-Sweet SF were stable for at least 60 days when stored in 2-oz amber plastic bottles at room temperature.

Stability of extemporaneously prepared glycopyrrolate oral suspensions

PURPOSE The stability of extemporaneously prepared glycopyrrolate 0.5-mg/mL suspensions was evaluated. METHODS An oral suspension of glycopyrrolate 0.5 mg/mL was prepared by thoroughly grinding 30 1-mg tablets of glycopyrrolate in a glass mortar. Thirty milliliters of Ora-Plus and 30 mL of either Ora-Sweet or Ora-Sweet SF were mixed and added to the powder to make a final volume of 60 mL. Three identical samples of the formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and stored at room temperature (23-25 °C). A 1-mL sample was withdrawn from each of the three bottles with a micropipette immediately after preparation and 7, 15, 30, 60, and 90 days afterward. After further dilution to an expected concentration of 50 μg/mL with sample diluent, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography. The samples were visually examined for any color change and evaluated for pH on each day of analysis. Taste evaluations were performed at the beginning and end of the study. Stability was defined as the retention of at least 90% of the initial concentration. RESULTS At least 95% of the initial glycopyrrolate remained throughout the 90-day study period in both preparations. There were no detectable changes in color, odor, taste, and pH, and no visible microbial growth was observed in any sample. CONCLUSION Extemporaneously compounded suspensions of glycopyrrolate 0.5 mg/mL in a 1:1 mixture of Ora-Plus/Ora-Sweet or Ora-Plus/Ora-Sweet SF were stable for at least 90 days when stored in amber plastic bottles at room temperature.

Stability of an extemporaneous alcohol-free melatonin suspension

PURPOSE The stability of alcohol-free oral suspensions of melatonin 1 mg/mL, extemporaneously prepared from two commercially available melatonin tablet products, was studied. METHODS Four 1-mg/mL melatonin suspensions were prepared. Formulations A and B contained 20 crushed 3-mg tablets of melatonin combined with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF to produce a volume of 60 mL. Formulations C and D were prepared by crushing 20 combination tablets containing melatonin 3 mg and pyridoxine hydrochloride 10 mg and then combining the powder with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF to produce a 60-mL volume. The suspensions were prepared in triplicate and stored at room temperature in amber plastic prescription bottles. Immediately after preparation and on days 7, 15, 30, 60, and 90, the samples were assayed in duplicate by stability-indicating high-performance liquid chromatography (HPLC). The samples were also evaluated for any changes in color, odor, and taste. RESULTS HPLC analysis demonstrated that at least 94% of the initial melatonin concentration in formulations A and B, and at least 98% of that in formulations C and D, remained throughout the 90-day study period. Detectable changes in color, odor, or taste occurred in all of the formulations. CONCLUSION Extemporaneously prepared, alcohol-free, 1-mg/mL suspensions of melatonin and melatonin-pyridoxine hydrochloride in a 1:1 mixture of Ora-Plus and either Ora Sweet or Ora Sweet SF were stable for at least 90 days when stored in 2-oz amber plastic bottles at room temperature.

Stability of extemporaneously prepared oxandrolone oral suspensions

PURPOSE The stability of extemporaneously prepared oxandrolone oral suspensions was studied. METHODS Oxandrolone oral suspension (1 mg/mL) was prepared using oxandrolone tablets, Ora-Plus, and either Ora-Sweet or Ora-Sweet SF. Three identical samples of each formulation were prepared and stored in 2-oz amber plastic bottles with child-resistant caps at room temperature (23-25 °C). After thorough but gentle shaking by hand to prevent foaming, a 1-mL sample was withdrawn from each of the six bottles, diluted with mobile phase to an expected concentration of 200 μg/mL, and assayed in duplicate by injecting 5 μL into the high-performance liquid chromatography system immediately after preparation and at 7, 14, 35, 60, and 90 days. The samples were examined for any change in color or pH on each day of analysis. The stability of the suspensions was determined by calculating the percentage of the initial oxandrolone concentration remaining on each test day. Stability was defined as the retention of at least 90% of the initial oxandrolone concentration. RESULTS At least 98% of the original oxandrolone concentration remained in both formulations at the end of the 90-day study period. There was no appreciable change in odor, taste, color, or pH. Both suspensions remained white in color and sweet with no aftertaste throughout the study period. The oxandrolone was easily resuspended with gentle shaking. CONCLUSION Extemporaneously prepared suspensions of oxandrolone 1 mg/mL in 1:1 mixtures of Ora-Plus and either Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 2-oz amber plastic bottles at room temperature.