Renal transplant patient compliance with free immunosuppressive medications.

BACKGROUND: Noncompliance with immunosuppressive medications after renal transplantation is believed to be a major cause of allograft rejection and graft loss, with the impressive costs of these agents considered a significant reason for noncompliance. Our purpose was to determine the compliance rates of renal transplant patients who received their immunosuppressant therapy free of charge and evaluate their patterns of compliance. METHODS: All patients who received a renal transplant and received their immunosuppressant medications at our institution for their first year posttransplant were included in the study. Compliance rate was calculated and serum immunosuppressant concentrations were obtained to validate compliance assessments. RESULTS: Eighteen patients were included in the study. Approximately 48% of noncompliant patients were found to have subtarget drug concentrations, although only 14% of compliant patients had subtarget levels (chi2=12.9, P<0.001). At 5 months posttransplant, 95% of the patients remained compliant; however, by 12 months posttransplant, only 48% of the patients remained compliant. The mean time to the first noncompliant month was 9.8 months (95% confidence intervals=8.60-11.0). CONCLUSIONS: Patients who received their immunosuppressants free of charge were generally compliant within their first year of transplantation, however, compliance tended to decrease over time. This suggests that drug cost alone does not explain noncompliant behavior. Intensive efforts to increase medication compliance before month 8 posttransplantation should be implemented.

Lack of effect of a high-fat meal on the volume of distribution of theophylline in humans.

The pharmacokinetics of intravenously administered theophylline were studied in five healthy nonsmokers. Each subject received 5 mg/kg of theophylline as aminophylline after an overnight fast and again after a standard high-fat meal. Although there was wide between-day variation in the elimination rate constant in three of the five subjects, no statistically significant differences were observed in area under the time-versus-concentration curve, maximum serum theophylline concentration, elimination rate constant, or apparent volume of distribution between the two treatments. A statistical power analysis indicated that if differences in volume of distribution and maximum serum theophylline concentration occur in the general population, the mean differences are less less than 15% and 20%, respectively. This suggests that alterations in intravascular drug distribution resulting from eating a high-fat meal do not contribute importantly to previously reported effects of food on serum theophylline concentrations after oral dosing.

Cost analysis of ardeparin versus enoxaparin for the prophylaxis of deep vein thrombosis after knee arthroplasty.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.

Pharmacoeconomic impact of a drug use evaluation of ceftriaxone in an acute-care medical center.

Inappropriate prescribing of antimicrobial agents may result in considerable expense to the health care system. It was noted in a 295-bed, acute-care medical center that ceftriaxone was being prescribed every 12 hours in what appeared to be a disproportionately large percentage of patients. A drug evaluation was conducted to determine the appropriateness of the prescribing of this agent. Based on indication, it was determined that a significant number of patients receiving a twice-daily dosing should receive once-daily dosing. An educational effort directed to the medical staff was implemented via the pharmacy and therapeutics committee on the proper prescribing of ceftriaxone. A follow-up drug use evaluation demonstrated appropriate prescribing in most situations, resulting in cost savings in excess of $25,000.

Pharmacist-managed aminoglycoside therapy in combination with a beta-lactam agent in the treatment of nosocomial pneumonia in critically ill patients.

We attempted to determine the outcome of treatment with aminoglycosides, dosed pharmacokinetically using traditional strategies, in combination with synergistic antibiotics in the management of nosocomial pneumonia in critically ill patients over a 1-year period. Twenty-three adults cared for in an intensive care unit received an aminoglycoside dosed by a pharmacist plus a beta-lactam antibiotic. Of these, 21 experienced clinical cure of the disease and 2 died of unrelated complications. No treatment failures were encountered. Therapy with aminoglycosides, dosed by traditional pharmacokinetic methods, in combination with synergistic antimicrobials, was effective in managing nosocomial pneumonia in this nontertiary care regional referral center.

Cost analysis of the American College of Chest Physicians guidelines for deep vein thrombosis prophylaxis in patients undergoing orthopedic arthroplastic surgery.

Guidelines for prophylaxis of deep vein thrombosis secondary to orthopedic surgery have been developed. In selecting a specific drug for formulary inclusion, it is ideal for an individual institution to determine the cost of therapy, as well as the frequency of adverse events and the cost of treating them for each agent undergoing consideration. Cost-effectiveness analysis using incremental cost-effectiveness ratios and sensitivity analyses are useful for determining which drug may be most cost effective.

Three Michaelis-Menten pharmacokinetic dosing methods compared with physician dosing of phenytoin in an outpatient neurology practice.

We compared predicted phenytoin serum concentrations using three Michaelis-Menten pharmacokinetic dosing methods with actual concentrations obtained from physician dosing in an outpatient neurology practice. Method 1 used population estimates for the Michaelis-Menten constant (Km) and maximum velocity (Vmax), method 2 used one dose and serum concentration pair to determine Vmax, and method 3 used two dose-concentration pairs to determine both Km and Vmax. In addition, physician doses were compared with pharmacokinetically calculated doses. Records of patients who received at least two phenytoin doses followed by two serum concentration determinations were reviewed. Data on age, gender, weight, physician doses, and resultant serum concentrations were collected. Pearson's correlation coefficient was used to compare physician maintenance doses with pharmacokinetically calculated predicted doses, whereas actual and predicted serum concentration data were used to determine precision and bias associated with each of the three methods. Actual serum concentrations fell into therapeutic range more frequently than predicted values in all but one comparison (method 3). Predicted and actual phenytoin doses were significantly correlated only with method 2. Only one of the three Michaelis-Menten pharmacokinetic dosing methods evaluated (method 3) was more predictive than physician phenytoin dosing.

Persistence with estrogen therapy in a postmenopausal Medicaid population.

We evaluated rates of persistence with estrogen replacement therapy in postmenopausal Georgia Medicaid recipients adjusted for age and race. Data files for 1992-1994 were examined to estimate 3-year conditional survival probabilities using the Kaplan-Meier model, and 3800 subjects were identified. Over 54% of women remained compliant over 29 months, and 17% continued therapy for the entire 35 months of observation. Kaplan-Meier predictors indicated that white women have a 70% chance of being compliant for 3 years, whereas black women have a 60% chance. Monthly discontinuation rates ranged from 1-1.5% after the second month of therapy. Younger, white women were the most likely to maintain and comply with therapy.

Improved health-related quality of life with SSRIs and other antidepressants.

STUDY OBJECTIVE: To document the health-related quality of life (HRQOL) of depressed patients receiving antidepressant drugs. DESIGN: Cross-sectional study. SETTING: Community pharmacy-based setting. PATIENTS: Fifty-seven depressed patients. INTERVENTION: Independent pharmacist members of the Community Pharmacists Research Network in Georgia administered the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to subjects. MEASUREMENTS AND MAIN RESULTS: Sixty-one percent of patients were treated with a selective serotonin reuptake inhibitor (SSRI) and 38.6% were treated with a non-SSRI. Those receiving SSRIs scored higher on the mean physical (PCS) and mental (MCS) health summary scores of the SF-36 than those not receiving the drugs. No significant differences were seen in PCS or MCS scores of men and women. CONCLUSION: Community pharmacists documented better HRQOL in patients receiving SSRIs than in those given other antidepressants.

The expanding role of pharmacy and therapeutics committees. The 1990s and beyond.

Traditionally, pharmacy and therapeutics (P&T) committees have been responsible for overseeing the drug use process, using formulary systems to control drug costs. Primarily, these committees act in an advisory capacity as policy-recommending bodies within healthcare systems, for the specific purpose of promoting rational drug therapy. Methodologies utilised by these committees include drug use evaluation, medical staff education, continuous quality improvement, formulary restriction and therapeutic interchange. Future roles of P&T committees will include the evaluation of clinical outcomes information, including quality-of-life issues, to establish policies governing the use of drugs at all levels and in all types of healthcare.

Formulary management of low molecular weight heparins.

Low molecular weight heparins (LMWHs) are increasingly being utilised as anticoagulants in healthcare settings. These agents offer several advantages over standard unfractionated heparin. Indications for LMWHs include deep vein thrombosis and pulmonary embolism prophylaxis, deep vein thrombosis treatment, use in coronary procedures associated with a high risk for bleeding, and in acute coronary syndromes. Prior to being added to formularies, LMWHs should be evaluated for efficacy, safety and economic benefits over other anticoagulants. Institutions should be prepared to conduct their own economic assessments in the absence of readily available studies. There is clear evidence that LMWHs are cost saving or are at least cost effective as thromboprophylactic agents in major orthopaedic surgery. The economic benefits of LMWHs in other surgical situations is less clear. Consistent evidence from several countries indicate that LMWHs are cost saving as anticoagulants for the initial treatment of DVT. Further studies are needed to evaluate the efficacy, safety and economics of LMWHs in other conditions besides hip and knee arthroplasty and general surgery.

Deep venous thrombosis prophylaxis in trauma: cost analysis.

Deep vein thrombosis and pulmonary embolism are major risks in patients experiencing major trauma. Currently, the American College of Chest Physicians recommends low molecular weight heparin as prophylaxis in trauma patients with identifiable risk factors in the absence of contraindications. Enoxaparin is the only low molecular weight heparin available in the US that has been evaluated to date in this indication. The purpose of this study was to perform incremental cost-effectiveness ratio calculations for enoxaparin versus no prophylaxis as thromboembolic prophylaxis in trauma patients. These calculations demonstrate that a cost of $279.43 would be incurred for each thromboembolic event avoided if enoxaparin 30 mg every 12 h were routinely used as prophylaxis in this population, compared with no prophylaxis. Sensitivity analyses demonstrate that if the incidence of proximal vein thrombosis in patients prophylaxed with enoxaparin approached 1.8%, if the actual rate of these thrombi exceeded 19.4% in untreated patients, or if the cost of the drug was decreased to $15.25 per dose, a cost saving would be experienced in routine prophylaxis with this agent.

Cost comparison of tinzaparin versus enoxaparin as deep venous thrombosis prophylaxis in spinal cord injury: preliminary data.

Thromboembolic events are major causes of morbidity and mortality in patients with spinal cord injuries. Low molecular weight heparins are recommended as prophylaxis against such events. The purpose of the current study was to perform a cost analysis of tinzaparin versus enoxaparin using published efficacy and safety data as deep vein thrombosis and pulmonary embolism prophylaxis in this population. All published English language articles evaluating either tinzaparin or enoxaparin as pharmacoprophylaxis in spinal cord-injured patients were identified. Data from these studies were subjected to cost-effectiveness analyses followed by sensitivity analyses to determine which agent is the most cost-effective in these patients. Results demonstrated that tinzaparin 3500 U daily and enoxaparin 30 mg every 12 h are both cost-effective agents for thromboembolism prophylaxis in patients with spinal cord injuries.

Achievement of anticoagulation by using a weight-based heparin dosing protocol for obese and nonobese patients.

The need for different heparin dosing protocols for obese and nonobese patients was studied. A chart review was performed for all patients who received heparin over an eight-month period at an acute care hospital. Data collected included age, sex, height, actual body weight (ABW), ideal body weight (IBW), initial activated partial thromboplastin time (aPTT), initial heparin bolus dose, initial heparin i.v. infusion rate, time to initial targeted aPTT, and final infusion rate. Forty patients met criteria for inclusion: 20 obese patients (greater than 30% over IBW) and 20 nonobese patients (less than 20% over IBW). Mean +/- S.D. initial heparin infusion rates for the obese and nonobese groups were 14.44+/-1.29 and 15.04+/-0.42 units/kg/hr, respectively. Times to targeted aPTT for obese and nonobese patients were 25.86+/-12.83 and 25.18+/-14.76 hours, respectively; mean final infusion rates were 12.94+/-2.56 and 12.36+/-2.54 units/kg/hr; and percent changes from initial to final infusion rates were 11.84% and 17.76%. There were no significant differences in initial or final infusion rates or time to targeted aPTT between the two groups. It is appropriate to use ABW in a weight-based heparin dosing protocol for obese patients.

Aminoglycoside dosing in the critical care patient: a case report of tertiary pharmaceutical care.

OBJECTIVE: To describe special dosage considerations for aminoglycoside antibiotics in critically ill patients from a pharmaceutical care perspective. DESIGN: Case report and discussion. SETTING: A nontertiary care regional medical center. PATIENT: A 21-year-old male college student involved in a moving vehicle accident who sustained a closed head injury and collapsed right lung with subsequent development of nosocomial pneumonia. OUTCOME MEASURES: Resolution of pneumonia and discharge from hospital. INTERVENTION: Tertiary level pharmaceutical care. RESULTS: Pneumonia resolved and patient was transferred to rehabilitation center. CONCLUSION: Tertiary pharmaceutical care provided by the pharmacist includes appropriate choice and monitoring of pharmacotherapy and pharmacokinetic drug dosing to promote good patient outcome.

Cost effectiveness of danaparoid compared with enoxaparin as deep vein thrombosis prophylaxis after hip replacement surgery.

Guidelines for prophylaxis of deep vein thrombosis (DVT) after hip replacement surgery suggest the use of twice-daily low-molecular-weight heparin as one treatment option. Danaparoid, a low-molecular-weight heparinoid, and once-daily enoxaparin are recently released dosage forms that have been evaluated as pharmacoprophylaxis for DVT after hip replacement surgery. Incremental cost-effectiveness ratio calculations using published efficacy and safety data suggest that enoxaparin (40 mg) daily is the more cost effective of these two agents as routine prophylaxis after hip replacement surgery.

Cost effectiveness of deep venous thrombosis prophylaxis after hip fracture.

Patients undergoing hip fracture repair are at significant risk for deep vein thrombosis and pulmonary embolism in the postoperative period without appropriate prophylaxis. Agents available in the United States that have undergone clinical trials as pharmacoprophylaxis for this indication include warfarin, dalteparin, and danaparoid. Safety and efficacy data from these trials were used to determine the most cost-effective agent for routine deep vein thrombosis prophylaxis in patients with hip fractures. Incremental cost-effectiveness ratio calculations demonstrate that warfarin dosed to an international normalized ratio of 2-2.7 is currently the most cost-effective agent in these patients.

Cost effectiveness of outpatient anticoagulant prophylaxis after total hip arthroplasty.

Guidelines for deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis have been developed for patients undergoing total hip arthroplasty (THA). Studies suggest that risk for developing these complications may exist for as long as 3 months following surgery. Cost-effectiveness analyses were performed on three pharmacoprophylaxis regimens administered over a 30-day period using literature-reported values for incidences of DVT and PE in patients postdischarge following THA. A cost savings of $21,466.89 will occur for each thromboembolic event avoided if low-dose warfarin daily is used routinely compared to enoxaparin 40 mg daily. Additionally, a cost savings of $18,618.10 is experienced if enoxaparin 40 mg daily for 4 days plus low-dose warfarin daily is administered versus enoxaparin 40 mg daily. Clinicians may choose to continue prophylaxis postdischarge with enoxaparin 40 mg daily for 4 days in combination with warfarin for 30 days in these patients until results of more definitive studies become available.

Depression associated with antihypertensive drugs.

BACKGROUND: Depression is a potential side effect of antihypertensive drug therapy. Consideration of this side effect is a reason often cited by physicians for not choosing certain drugs. METHODS: In this prospective study the relative rates of depression were measured by the Zung Self-Rating Depression Scale (SDS) in patients from four hypertension treatment groups. Treatment groups consisted of 466 patients receiving: (1) no drug therapy, (2) diuretics only, (3) diuretics plus reserpine, and (4) diuretics plus beta-blockers. Demographic data including age, sex, and race were collected. Analysis of variance was used to compare the rate of depression among the treatment groups, as well as among age, sex, and racial groups. RESULTS: Using a Zung SDS index of greater than or equal to 50, 35.4% of the hypertensive population was depressed. Age and sex were not significant factors in the frequency of depression. Blacks scored higher than whites in all drug treatment groups except those treated with high lipophilic beta-blockers, but the rate of depression was not higher. Whites on the lowest dose of reserpine had the lowest rate of depression. The rate of depression among those taking reserpine or beta-blockers was no different than that among those receiving either no treatment or diuretics. CONCLUSIONS: Reserpine or beta-blocker therapy did not cause any more depression than any other antihypertensive treatment.