Histamine receptor antagonists and lipid stability in total nutrient admixtures

Drug stability and compatibility studies should be performed for all medications added to total nutrient admixtures (TNAs) before administration to patients. The stability of TNA components will vary depending on product selection and final concentrations. This variability prohibits generalizing published study results generically to TNAs containing untested products or combinations. Histamine receptor antagonists (H2RAs) are commonly administered by continuous infusion via nutrient solutions. When the delivery vehicle is a TNA, comparative stability and compatibility studies performed under similar test conditions are lacking. The stability of marketed parenteral H2RAs and of the investigational H2RA, nizatidine was analyzed in TNA solutions containing either Liposyn II or Intralipid at differing concentrations. All H2RAs remained at more than 90% of initial concentration at 24 hours. After 48 hours, only ranitidine concentrations fell to less than 90% in all study solutions. Each TNA containing an H2RA was within pH stability ranges for lipid products, and no change in particle size was detected during the 48-hour period. This is the first report determining H2RA compatibility and stability in TNA solutions with both 3% and 5% Intralipid and Liposyn II and using similar methodology for all standard H2RA concentrations. Results suggest that these drugs are stable for 24 hours in TNAs containing either lipid product. Beyond this time, administration of ranitidine may be unreliable because of poor stability under the conditions tested.