Oxycodone hydrochloride immediate-release analgesic for managing severe pain: abuse-deterrent formulations.

This paper is an expert opinion in response to the development of abuse-deterrent immediate-release tablets containing oxycodone HCl. There is a potential impact, both positive and negative, of this type of dosage form on patients, those suffering from the disease of addiction, health care providers, and the cost of health care.

Proton-pump inhibitors for gastric acid-related disease.

Proton-pump inhibitors are the most effective drugs introduced to date for suppressing gastric acid production. Although they are used to treat the same conditions as histamine type-2 receptor antagonists, they differ from the latter drugs in how they inhibit acid production, and in how they should be given. Initial concerns over potential ill effects of hypergastrinemia due to long-term acid suppression with proton-pump inhibitors have been unfounded.

Characteristics and outcomes of patients who self-extubate from ventilatory support: a case-control study.

OBJECTIVE: To identify factors associated with the occurrence of deliberate self-extubation and to describe associated patient outcomes. DESIGN: Case-control study. SETTING: ICUs of a national referral, tertiary medical center. PARTICIPANTS: Fifty adult, intubated patients who had self-extubated from mechanical ventilatory support. Two control subjects who had not self-extubated were matched to each case based on age, gender, primary discharge diagnosis, and time hospitalized (within same quarter). MEASUREMENTS: Standardized coding of medical record information, including demographic characteristics, clinical information, intubation and mechanical ventilation characteristics, medications, and selected laboratory indexes. RESULTS: As compared to the control subjects, patients who self-extubated were more likely to be medical than surgical patients (p<0.001) and have a current history of smoking (p<0.05). Prior to the self-extubation, patients had a greater likelihood of hospital-acquired infections (p<0.001) or other hospital-acquired adverse events (p<0.001), abnormal (<10, >50 mg/dL) BUN (p<0.05), and abnormal (<20, >50 mm Hg) PaCO2 (p<0.05); they also were more likely to be restless or agitated (p<0.001), and more likely to be physically restrained (p<0.001). A logistic regression model demonstrated that presence of restlessness or agitation and presence of a hospital-acquired adverse event were independently associated with self-extubation from mechanical ventilatory support. In examining outcomes, as compared to the control subjects, those who self-extubated had longer lengths of stay in ICU and hospital, were more likely to need reintubation, and were more likely to suffer complications from intubation. However, none of the cases died within 48 h of self-extubation. CONCLUSION: The results underscore the need for clinical guidelines for weaning and for monitoring patients at risk of self-extubation.

Adverse reactions to sedative/hypnotics: three years' experience.

Reported adverse reactions to orally administered sedative/hypnotics were systematically recorded during a 3-year period in a 1,000-bed teaching hospital. Reported cases were reviewed by a multidisciplinary committee and then by a pharmacist, and judgments were made as to type, severity, and outcome of adverse reactions. Probability that the reaction was caused by the medication was recorded in terms of both a global judgment and a systematic scale. The frequency of adverse reactions was calculated as a percentage of total doses of each agent dispensed by the pharmacy during the same time period. The assessment of benzodiazepine sedative/hypnotics indicated that adverse reactions were rare, ranging from frequencies of 0.05% of doses administered (lorazepam) to none (chlorazepate). The median frequency of reported adverse reactions was 0.01%, or 1 in 10,000 doses. The vast majority of reactions could be viewed as extensions of the therapeutic effect, were considered mild, and were without sequelae. All adverse reactions occurred in patients over 55 years old except for four patients under age 50 who received lorazepam. There were no reported cases of violent behavior or global amnesia.

Comprehensive therapeutic interchange program in a community hospital.

The implementation of a comprehensive therapeutic interchange program is described. The need to reduce the number of telephone calls to physicians about nonformulary drug orders, reduce drug costs, and maximize the effectiveness of drug therapy prompted the development of an automatic therapeutic interchange program at a 273-bed nonteaching community hospital. Pharmacists and physicians agreed that a telephone call to discuss every nonformulary drug order was unnecessary. The pharmacy department presented the automatic interchange program to the pharmacy and therapeutics committee. The program was reviewed by the committee, the hospital attorney, and medical staff members and was instituted in 1986 for drug products, such as vitamins and antacids, for which interchanges are noncontroversial. A newsletter describing the program was distributed, and inservice education sessions were held. A reminder was placed on order forms that an interchange for nonformulary drugs would be made unless the nonformulary agent was deemed "medically necessary" by the physician. In such cases, the physician is contacted to discuss the therapeutic alternative. As acceptance of the program and cost efficiencies were demonstrated, more controversial agents were phased in during subsequent years. It was difficult to obtain approval to add some agents, such as third-generation cephalosporins, to the program, but noncompliance and confusion have been minimal. An automatic therapeutic interchange program has worked well at this institution since 1986.

Implementing therapeutic interchange of intravenous famotidine for cimetidine and ranitidine.

The steps taken to implement a therapeutic interchange program for i.v. histamine H2-receptor antagonists and to determine the potential cost savings are described. A literature review conducted by pharmacists at a 273-bed nonteaching community hospital showed that i.v. famotidine was as safe and effective as i.v. cimetidine or ranitidine and that it was feasible to add famotidine to total parenteral nutrition (TPN) solutions. Because of famotidine's cost advantage, it was proposed that i.v. famotidine be used in place of specific dosage regimens of i.v. ranitidine or cimetidine and in TPN solutions ordered for patients receiving concurrent H2-antagonist therapy. The approval of the hospital attorney and hospital gastroenterologists was secured, and a formal proposal was submitted. The pharmacy department distributed a memorandum describing the advantages of famotidine, conducted inservice education sessions, and sought the compliance of physicians by placing reminders on order forms and patient charts and by contacting physicians directly. The program was implemented in May 1989. During the first three months, only one physician insisted that patients receive i.v. ranitidine rather than famotidine. It was projected that the interchange of i.v. famotidine for cimetidine or ranitidine would result in a total savings of $37,565 during the first year due to reductions in the cost of drugs, supplies, and nursing labor. The acceptance of a therapeutic interchange program for H2 antagonists was excellent, and the projected savings are substantial.

Pharmacokinetics of theophylline in infants with bronchiolitis.

Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks-6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0-8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5-5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5-1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48-21.6 micrograms/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children greater than 1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.