Chemical and visual stability of amphotericin B in 5% dextrose injection stored at 4 degrees C for 35 days.

The chemical and visual stability of amphotericin B in 5% dextrose injection under refrigeration was assessed. Three admixtures of amphotericin B 0.1 mg/mL in 5% dextrose injection and three admixtures of amphotericin B 0.25 mg/mL in 5% dextrose injection were aseptically prepared in polyvinyl chloride (PVC) bags. Immediately after preparation (at time zero), six 5-mL samples were aseptically transferred from each admixture to sterile collection tubes. Three of the samples from each admixture were quick-frozen for later assay by stability-indicating high-performance liquid chromatography (HPLC), and the other three were immediately assessed for pH. Each of the six admixtures was also assessed visually under fluorescent light and 2x magnification for color change, turbidity, gas evolution, and precipitation. The admixtures were stored in PVC bags at 4 degrees C and protected from light. Six 5-mL samples were withdrawn from each admixture at 10, 21, and 35 days. Three of the samples from each admixture were assessed for pH, and three were quick-frozen for subsequent HPLC assay. There was no substantial loss or deterioration of amphotericin B during the 35-day study. At no time was the mean concentration of amphotericin B in the samples less than 96.4% of the concentrations at time zero for the 0.1-mg/mL samples or less than 96.6% of the time zero concentrations for the 0.25-mg/mL samples. There were no appreciable changes in pH, and there was no visual evidence of instability in any of the samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability and compatibility of ganciclovir sodium in 5% dextrose injection over 35 days.

The stability and compatibility of ganciclovir sodium in 5% dextrose injection over 35 days were assessed. Nine admixtures of ganciclovir sodium 1, 5, and 10 mg/mL in 5% dextrose injection were aseptically prepared. Immediately thereafter, six samples were aseptically withdrawn from each admixture into sterile collection tubes. Three of the samples were frozen for stability-indicating high-performance liquid chromatographic (HPLC) assay at a later date, and the other three were immediately assessed for pH. Each admixture was also assessed visually for color change, turbidity, gas evolution, and precipitation. The admixtures were stored in the dark at 4-8 degrees C and sampled at 10 and 35 days. There was no significant loss of ganciclovir over the 35-day study period. No admixture at any time contained less than 93.4% or more than 103.7% of its initial ganciclovir concentration. There were no appreciable pH changes, and there was no evidence of visual incompatibility. Ganciclovir sodium 1, 5, and 10 mg/mL in 5% dextrose injection was stable for at least 35 days when stored in the dark at 4-8 degrees C.

Parenteral nutrient admixtures as drug vehicles: theory and practice in the critical care setting.

Parenteral nutrient (PN) admixtures are the most complex, extemporaneously compounded formulations routinely prepared for hospitalized and home-based patients. In addition, drugs are added with increasing frequency to PN admixtures, thus presenting even greater physicochemical challenges to this highly complex pharmaceutical product. The continuous infusion of selected drugs may provide pharmacokinetic and therapeutic advantages over conventional, intermittent, bolus methods of administration. Fluid conservation, cost savings, and a possible decrease in the risk of infection through reduced catheter manipulation and simplification of therapy provide additional incentives to consider the use of PN admixtures. The many advantages of PN admixtures make them an attractive approach to cost-effective care, with special clinical benefits achieved in the critical care setting. This article reviews our clinical experience using PN admixtures as drug vehicles for selected drugs and presents some theoretical as well as actual benefits associated with this practice.

Home intermittent amrinone infusions in terminal congestive heart failure.

The prevalence of congestive heart failure (CHF) and its progressive degenerative course continue to generate pressure for alternative, more effective means of treatment. A confluence of factors, including the number of Americans with CHF, the spiraling costs of hospital care, and increasing interest in cost-effective home care, contribute to the current efforts to develop an effective, nontoxic therapy that effectively increases myocardial contractility and output and can be administered within the confines of the home. Given that preliminary clinical trials in the hospital setting with amrinone have produced positive results, the transition of this therapy to the home, when administered intermittently via central venous catheter and infusion pump, was undertaken. In order to prolong and increase quality of life in terminal CHF patients, intermittent amrinone infusions were provided at home to four patients as part of our pilot program. All four patients met the criteria for New York Heart Association (NYHA) functional class IV heart failure, and none had responded to conventional therapy suitable for outpatient maintenance. The patients also shared strong family support and an intense desire to improve the quality of remaining life. All four patients and designated family members were trained in the specifics of aseptic technique, medication dose preparation, central venous catheter care, and operation of an infusion pump. An ambulatory pump was used in three of the four patients. Subsequent to the initiation of intermittent home amrinone infusions, all four patients had greater tolerance to limited exercise and/or ambulation secondary to increased cardiac output and diuresis. Patients survived 8, 10, 47, and 56 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability and compatibility of cimetidine hydrochloride and aminophylline in dextrose 5% in water injection.

A controlled study was conducted to assess the physical compatibility of cimetidine hydrochloride (HCl) and aminophylline and the chemical stability of an admixture of the two medications in dextrose 5% in water (D5W) injection, over 48 hours at room temperature. Three one-liter admixtures were prepared, each containing cimetidine HCl 1200 mg and aminophylline 500 mg in D5W. One liter of only cimetidine HCl 1200 mg in D5W and one liter of only aminophylline 500 mg in D5W served as controls. Samples drawn from the five admixtures and immediately frozen were analyzed for cimetidine and theophylline content at times 0, 1, 6, 24, and 48 hours using high-performance liquid chromatography. Chemical stability of each drug was assessed relative to its time-zero concentration. Samples were also drawn from each test and control solution at every time interval to assess the pH. Admixtures were stored at room temperature out of direct sunlight for the duration of the study, and were visually inspected for color change, turbidity, cloudiness, and precipitation. Recovery of cimetidine and theophylline at all test intervals, pH assessments, and visual inspections of the admixtures showed that cimetidine HCl and aminophylline are both chemically stable and physically compatible for 48 hours at room temperature in one liter of D5W.

Role of histamine (H2)-receptor antagonists in total parenteral nutrition patients.

Hospitalized patients, especially those who are critically ill, are often at risk for malnutrition and may require nutritional support. Although the enteral approach is generally preferred when providing nutritional support, parenteral nutrition is frequently required. These patients are also likely to receive therapeutic or prophylactic parenteral histamine (H2)-receptor antagonists. Patients receiving both total parenteral nutrition and parenteral H2-receptor antagonists may benefit from receiving the drug in combination with the total parenteral nutrition admixture. Parenteral cimetidine and ranitidine are stable in various total parenteral nutrition fluids. Clinically, cimetidine has been studied more extensively than ranitidine. Clinical benefits and cost savings may be realized from this method of drug delivery.

Drug stability guidelines for a continuous infusion chemotherapy program.

Recent technological advances in ambulatory infusion pumps, the development of safe long-term venous access devices, and the clinical advantages of the continuous infusion of chemotherapeutic agents have facilitated the delivery of ambulatory infusion chemotherapy. This method of therapy provides chemotherapeutic drug infusions over a period of several days, weeks, or months. Therefore, the antineoplastic drugs used must be chemically stable for the duration of the infusion. However, an extensive compilation of extended stability (greater than 24 hours) data of intravenous solutions containing antineoplastic drugs is lacking, and as such, pharmacy concerns have been significant. We have accumulated extended chemical stability data (greater than or equal to 90% of time zero concentration) based on literature surveys and manufacturer written correspondence. The accumulated data, presented herein, support the following minimum stability limits (in days) with regard to single and multiple drug admixtures stored in 60-ml polyvinylchloride (PVC) reservoir bags (Cormed, Medina, NY) at room temperature: cytarabine (8), cyclophosphamide (6), doxorubicin (14), epidoxorubicin (14), floxuridine (8), fluorouracil (14), methotrexate, mitomycin-C (14), cisplatin (14), thiotepa (7), vinblastine (8), methotrexate/fluorouracil (14), doxorubicin/vinblastine (8), doxorubicin/cyclophosphamide (7), fluorouracil/cyclophosphamide (7), and doxorubicin/vincristine (14).

Infusion phlebitis associated with a programmable syringe-pump system versus gravity-feed minibottles.

The occurrence of infusion phlebitis in patients receiving intravenous antibiotics via a gravity-feed minibottle system versus a new syringe-pump system was compared. Patients at least 18 years old who had indwelling intermittent injection sites inserted for medication administration were randomized to either the minibottle system or the syringe-pump system. Antibiotics in minibottles were diluted in 50-100 mL of 5% dextrose injection; in the syringe-pump group, aminoglycoside antibiotics were diluted in 0.9% sodium chloride injection and all other antibiotics were diluted in sterile water for injection. Antibiotics were not piggybacked into running primary infusions in any of the study patients, and no other medications except for 0.9% sodium chloride flushes were administered through the catheters. All catheters were inserted in peripheral veins and evaluated for phlebitis by i.v. nurse specialists using standardized criteria. Catheters were changed upon the occurrence of grade 1 phlebitis or after a period of three days without the development of phlebitis. Over an 18-week period, 85 catheter sites (53 syringe-pump group versus 32 minibottle group) were evaluated in 30 patients (14 syringe-pump group versus 16 minibottle group). The mean +/- S.D. catheter life in both groups was 50.6 +/- 20 hours. Phlebitis occurred in 62% of syringe-group sites versus 66% of minibottle-group sites; the incidence and severity of phlebitis were not significantly different between groups. The majority of catheter sites were infused with cefazolin sodium. The potential for phlebitis using the syringe-pump system in this study appears to be similar to that of the gravity-feed minibottle system when appropriate diluents, diluent volumes, and infusion rates are used.

Practical considerations regarding the use of total nutrient admixtures.

The biological concerns, proper storage and administration, and advantages of using total nutrient admixtures (TNAs) for nutritional support are reviewed. In 1983, FDA approved lipid emulsions for administration with dextrose and selected crystalline amino acid preparations (known as three-in-one or total nutrient admixtures). The stability of TNAs is affected by pH, order of mixing, and temperature. Conflicting results have been reported on the issue of microbial growth potential in TNAs. At room temperature, the delivery of the TNA infusate should not exceed 24 hours. Plastic containers that do not contain diethylhexyl phthalate, in sizes up to 3 L, are practical and safe for administration of TNAs. The efficiency of an institution's volumetric pumps should be evaluated before converting to a TNA system because the low final concentrations of lipid emulsion present in the admixtures may render certain pumps inoperable. The practical, nutritional, and potential economic benefits of a TNA delivery system support its use. Further research is needed to determine microbial growth potential, electrolyte and drug compatibilities, and stability under prolonged storage of these admixtures.

Microbial contamination potential of solutions in prefilled disposable syringes used with a syringe pump.

The sterility of trypticase soy broth (TSB) that was frozen and thawed in disposable plastic syringes and infused via syringe pump was studied to determine whether ambient air or personnel-transferred contaminants compromised the sterility of the solution. Samples of TSB (10, 20, 30 mL) were prepared aseptically in syringes of three different brands--150 samples for each volume (50 for each manufacturer). The syringes were placed in zip-lock bags, stored for 24 hours at -15 to -20 degrees C, and thawed for three hours. Both positive and negative controls were used. For the test samples, infusion sets were connected to the syringes under aseptic conditions, and the solution was infused via syringe pump in ambient air into polyvinyl chloride minibags before incubation. The remaining samples were prepared in the same manner as the test solutions except that they were intentionally challenged with Bacillus subtilis introduced distal to the plunger. All samples were inspected visually for turbidity after a 14-day incubation period. There was no growth in any of the test infusion samples or in samples that were intentionally contaminated. The negative controls showed no growth; all of the positive controls showed growth. The sterility of solutions frozen in disposable plastic syringes does not appear to be compromised by touch contamination of the plunger shaft or by airborne microorganisms settling on the infusion system.

Cimetidine and parenteral nutrition in the ICU patient.

Cimetidine is often prescribed for hospitalized patients requiring intravenous nutritional support (ie, total parenteral nutrition). When administered parenterally, the drug may prevent excessive fluid and electrolyte loss in patients with short-bowel syndrome, particularly after resection. It may also help prevent anastomotic ulcers in patients following partial gastrectomy. In patients with hypersecretory disease or high-volume ostomy drainage, cimetidine is clinically useful in moderating secretions, thus reducing fluid and electrolyte loss. Cimetidine can prevent, and perhaps treat, metabolic alkalosis associated with significant losses of nasogastric aspirate. Intravenous administration of the drug to patients requiring nasogastric suction often eliminates the need for addition of hydrochloric acid to their parenteral nutrition admixtures. Cimetidine has been found to be physically compatible and chemically stable in crystalline amino acid/dextrose solutions and in crystalline amino acid/dextrose/lipid admixtures. As cimetidine is widely used in patients receiving total parenteral nutrition, it has become acceptable practice to deliver the drug via parenteral nutrition admixtures. Admixing the drug may be of particular advantage for patients with limited vascular access or for those who are fluid restricted. Cimetidine when given by continuous infusion may be more effective and require less drug per day than if administered via intermittent injection. Moreover, administration of cimetidine by continuous infusion to hyperalimentation patients has been documented to save the institution more than $22,000 a year in materials and labor costs.

Stability of cimetidine hydrochloride in a total nutrient admixture.

The stability of cimetidine hydrochloride in a total nutrient admixture was studied. A total nutrient admixture composed of 5% amino acid injection, 20% dextrose injection, and 3% intravenous fat emulsion was prepared aseptically in four 2-L ethylene-vinyl acetate bags. Cimetidine hydrochloride injection was added to three of the admixtures to yield final cimetidine concentrations of 600, 1200, and 1800 mg per 1500 mL of admixture; the fourth admixture served as a control. At 0, 24, and 48 hours, cimetidine content was measured by high-performance liquid chromatography, and the admixtures were tested for pH and visually inspected for signs of creaming, oiling out, or phase separation. Particle-size distribution in the admixtures was compared with that in 20% intravenous fat emulsion. No appreciable changes in cimetidine concentration or pH occurred over 48 hours, and no visual changes were observed. Particle sizes were comparable to those in the 20% intravenous fat emulsion control except in the admixture containing cimetidine hydrochloride 600 mg, which had significantly more particles larger than 9.9 microns at 48 hours. In the total nutrient admixture studied, cimetidine hydrochloride in concentrations up to 1800 mg per 1500 mL was stable for 24 hours at room temperature, and the lipid emulsion was apparently not altered during this period by cimetidine.