-- Back to Table of ContentsStudy Objective. To increase the response rate to hepatitis B vaccine in patients awaiting lung transplantation.
Design. Historically controlled, open-label study.
Setting. Lung transplant clinic at a university hospital.
Subjects. Twenty-seven consecutive individuals with end-stage pulmonary disease who were enrolled to accrue 15 subjects who would complete the vaccine series before transplantation; and 27 lung transplant recipients who were immunized with the conventional dose before the study and served as historical controls.
Intervention. Intramuscular injection of high-dose hepatitis B vaccine 40 µg at 0, 1, and 6 months.
Measurements and Main Results. Hepatitis B surface antibody (anti-HBs) concentrations were measured 1-2 months after completing the high-dose series. Individuals with undetectable anti-HBs received additional vaccine to a maximum of six doses. The response rate to the series was compared with that in the control group. Seventeen individuals in the high-dose group and 14 controls met the study criterion of complete vaccine series before transplantation. The former had a much higher response rate than the latter (9 [53%] vs 1 [7%], p<0.01). Four of six patients who received additional doses of vaccine seroconverted. Two of them underwent transplantation shortly after completing the three-dose series.
Conclusion. The high-dose hepatitis B vaccine series produced a protective immune response in lung transplant recipients; however, the response was suboptimal, and alternative immunization strategies should be studied.
(Pharmacotherapy 2003;23(5):555-560)
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Study Objectives. To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation.
Design. Double-blind, randomized, placebo-controlled, crossover study.
Setting. Respiratory clinic and clinical research center.
Subjects. Twelve women with documented premenstrual asthma (> 20% premenstrual worsening of asthma symptoms and/or of peak expiratory flow [PEF] during a 1-month screening phase.
Intervention. Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 (i.e., premenstrually, or before the onset of menses) in the first cycle and then crossed over to the other arm in the second cycle. Throughout both cycles, the women recorded daily morning and evening PEF readings and asthma symptoms.
Measurements and Main Results. Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 (follicular phase), 22 (luteal phase), and 28 (premenstrually) of both the estradiol and placebo cycles. During the two premenstrual visits, the Asthma Quality of Life Questionnaire was administered. No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores. The area under the curve (AUC) for the composite asthma symptoms versus time profile was numerically, but not statistically, lower (denoting less severe symptoms) during the estradiol cycle than during the placebo cycle. Likewise, no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle. Despite differences (p<0.05) in day-28 estradiol concentrations for estradiol and placebo cycles, no significant differences were found in forced expiratory volume in 1 second, serum endothelin-1, serum and urine eosinophil protein X, urine leukotriene E4, or quality-of-life scores.
Conclusion. Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control. As in the case of premenstrual syndrome, the placebo effect may be prominent in premenstrual asthma. Further trials, involving women with more severe asthma under poorer control, are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation.
(Pharmacotherapy 2003;23(5):561-571)
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Study Objective. To evaluate the toxicity of amphotericin B deoxycholate formulations.
Design. In vitro experiment.
Setting. University research center.
Material. Human mononuclear THP-1 cells.
Intervention. The human mononuclear cells were exposed in vitro for 2 hours to the following deoxycholate formulations of amphotericin B, in 2.5- and 5-µ/ml concentrations: Apothecon, Pharmacia, Sigma, Gensia, Pharma-Tek, and VHA.
Measurements and Main Results. Toxicity of the amphotericin B formulations were assessed by measuring interleukin (IL)-1b expression in an in vitro model. Amphotericin B content was measured by enzyme-linked immunosorbent assay (ELISA), and amphotericin A and B contents were assessed by spectrophotometry. Endotoxin contamination was evaluated in all reagents. Expression of IL-1b from Sigma, Pharmacia, and Pharma-Tek formulations was increased approximately 250%, 50%, and 25%, respectively, compared with amphotericin A. Amphotericin B content of Sigma, Pharmacia, Pharma-Tek, and Gensia formulations, as measured by ELISA, was increased approximately 450%, 200%, 200%, and 100%, respectively, compared with Apothecon. This variation could not be explained by differences in amphotericin A or B content as measured by spectrophotometry.
Conclusion. Amphotericin B is obtained from a fermentation plant and manufactured as a pharmaceutical at different facilities. Both previous clinical observations and the current in vitro evaluation revealed significant differences among the formulations. Likely, other polyenes or pyrogenic toxins in differing amounts are in these formulations, thus explaining the variability in toxicity observed among the formulations.
(Pharmacotherapy 2003;23(5):572-578)
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Study Objective. To determine whether urinary 11-dehydrothromboxane B2 (d-TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite.
Design. Randomized, crossover study.
Setting. Two outpatient clinical centers.
Patients. Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation.
Intervention. Levels of serum thromboxane B2 and d-TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks.
Measurements and Main Results. During treatment with aspirin 325 mg/day, the mean ± SD serum thromboxane B2 level was 0.9 ± 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB2 was 16 ± 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB2 was 4.4 ng/mmol creatinine.
Conclusion. Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.
(Pharmacotherapy 2003;23(5):579-584)
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Study Objective. To develop a gentamicin pharmacokinetic population model and once-daily dosing algorithm for neonates younger than 10 days.
Design. Prospective, open-label study.
Setting. Neonatal intensive care unit.
Patients. One hundred thirty-nine neonates prescribed gentamicin.
Measurements and Main Results. Gentamicin peak and trough serum concentrations were collected from 139 neonates divided into three groups who were receiving one of the following intravenous 24-hour gentamicin regimens during the first 10 days of life, based on gestational age and birth weight (group 1, < 28 wks, 2.5 mg/kg; group 2, 28-34 wks, 3 mg/kg; and group 3, > 34 wks, 4 mg/kg). A structural model was developed in ADAPT II software using a MAP Bayesian approach. Final population parameter estimates were calculated using iterative two-stage analysis. The median (range) gestational age and birth weight, respectively, were 32 weeks (23-42 wks) and 1.92 kg (0.47-5.00 kg). The final one-compartmental linear model had a median (range) gentamicin total clearance, half-life, and volume of distribution of 0.0709 L/hour (0.0151-0.246 L/hr), 8.59 hours (4.88-16.9 hrs), and 0.262 L (0.0903-0.929 L), respectively. Total clearance increased as gestational age increased (p<0.001). Group 1 (10.2 hrs) had a significantly longer half-life than either group 2 (8.89 hrs, p<0.01) or group 3 (6.98 hrs, p<0.01). Total clearance was associated with gestational age and birth weight: clearance (L/hr) = (0.00504 + [0.00108 • gestational age]) • birth weight (coefficient of determination [r2] = 0.897), and volume of distribution was associated with birth weight (r2 = 0.700). The following dosing algorithm was designed to reach a therapeutic 24-hour area under the curve (87.5 mg/L•hr) in neonates during the first 10 days after birth: 24-hour gentamicin dose (mg) = (0.441 + [0.0945 • gestational age]) • birth weight.
Conclusion. This dosing algorithm provides a new approach for determining initial gentamicin dosing regimens in neonates; however, clinical validation is required.
(Pharmacotherapy 2003;23(5):585-591)
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Study Objective. To determine the population pharmacokinetic parameters of enterally administered fluconazole in patients in a surgical intensive care unit (SICU).
Design. Population pharmacokinetics component of a prospective, randomized clinical study.
Setting. The SICU at a university hospital.
Patients. One hundred ten patients with an expected length of stay in the SICU of 3 or more days and a need for intubation, in whom at least one fluconazole plasma concentration-time measurement was available.
Intervention. Patients received fluconazole as an 800-mg loading dose and as a 200- or 400-mg (depending on renal function) daily maintenance dose. Fluconazole suspension was administered enterally followed by a 30-ml free water flush.
Measurements and Main Results. Plasma samples were collected, and population pharmacokinetic analysis was performed with NONMEM software; a one-compartment pharmacokinetic model was used. Fluconazole clearance was dependent on creatinine clearance, and volume of distribution was dependent on body weight and age. In patients with creatinine clearance values greater than 80 ml/minute, between 30 and 80 ml/minute, and less than 30 ml/minute, geometric mean (percentage coefficient of variation) fluconazole clearance was 14.39 ml/minute (21%), 10.53 ml/minute (28%), and 5.47 ml/minute (30%), respectively. The geometric mean (percentage coefficient of variation) volume of distribution in all patients was 1.27 L/kg (28%) and decreased with increasing age.
Conclusions. Fluconazole clearance values in patients in the SICU who had normal renal function and in those with renal impairment were in agreement with previously reported data. Fluconazole volume of distribution was larger and half-life was longer in the SICU population than in healthy subjects.
(Pharmacotherapy 2003;23(5):592-602)
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Study Objective. To measure the influence of different surface area:volume ratios (SA:Vs) on antibiotic penetration and subsequent antibacterial effect.
Design. In vitro laboratory experiment.
Setting. Two academic research laboratories.
Intervention. The two models with effective SA:Vs of 5.34 and 4.80 cm-1 were evaluated by conducting a time-kill experiment with Pseudomonas aeruginosa ATCC 27853 and ceftazidime.
Measurements and Main Results. Ceftazidime was administered by constant infusion into the central compartment. Its penetration into the peripheral compartment and bacterial counts were determined over 24 hours, and antibacterial effect was quantified. Antibiotic penetration, calculated using central compartment and peripheral compartment area under the concentration-time curves, and effect, quantified as the relationship between the areas under growth and kill curves, differed between the models. Antibiotic penetration into the peripheral compartment was 53% greater over the first 4 hours of the experiment in the model with the larger SA:V. This was associated with antibacterial effects that were 64% and 38% greater in the 0-4-hour and 0-24-hour time periods, respectively.
Conclusion. Differences in antibiotic penetration and effect observed between these models are likely explained by differences in SA:V.
(Pharmacotherapy 23(5):603-608)
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Study Objectives. To assess the prevalence of illicit methylphenidate use among undergraduate college students at a large university, and to identify alcohol and other drug use behaviors, as well as the negative consequences and risk factors, associated with illicit methylphenidate use.
Design. Internet survey.
Setting. Large public university.
Subjects. Thirty-five hundred randomly selected undergraduate students.
Measurements and Main Results. Of the 2250 students who completed the survey, 3% reported past-year illicit methylphenidate use. Illicit methylphenidate users were significantly more likely to use alcohol and drugs and report adverse alcohol- and drug-related consequences than prescription stimulant users or students who did not use stimulants. Undergraduate men and women were equally likely to report past-year illicit methylphenidate use. Weekly party behavior was significantly associated with past-year illicit methylphenidate use.
Conclusion. Illicit use of prescription-only stimulants on college campuses is a potentially serious public health issue. More work is needed to promote understanding and awareness of this problem among clinicians and researchers.
(Pharmacotherapy 2003;23(5):609-617)
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Study Objectives. To compare the use of b-lactams and subsequent Pseudomonas aeruginosa sensitivity patterns before and after implementation of a clinical pharmacist-facilitated antimicrobial restriction program in August 1997.
Design. Retrospective consecutive data collection.
Setting. Large university-affiliated medical center.
Intervention. The study results are the accumulation of the daily intervention activities of the antimicrobial restriction program. Data on antimicrobial grams purchased/1000 patient-days and susceptibility patterns were collected and analyzed retrospectively.
Measures and Main Results. Annual grams of ceftazidime, piperacillin, piperacillin-tazobactam, and other antipseudomonal b-lactams purchased/1000 patient-days were compared during the 2 full calendar years before the antimicrobial restriction program (1995-1996) with the 4 full calendar years after the program was implemented (1998-2001). Pseudomonas aeruginosa resistance trends for the antipseudomonal b-lactams, ciprofloxacin, and tobramycin also were compared for the 2 years before the program (1995-1996) with the last 2 years of the program (2000-2001). A 44% reduction in ceftazidime use was documented; ostensibly, minimal changes occurred in the overall use of piperacillin and piperacillin-tazobactam. During the same time period, ceftazidime resistance fell from 24% to 11.8% (p<0.001), whereas piperacillin resistance fell from 32.5% to 18.5% (p<0.001). Imipenem resistance declined from 20.5% to 12.3% (p<0.001) with an 18% reduction in use. Aztreonam resistance declined from 29.5% to 16.5% (p<0.001) despite a 57% increase in use. No changes in resistance to either ciprofloxacin or tobramycin were found.
Conclusion. Through an antimicrobial restriction program, a dramatic reduction in ceftazidime use was achieved with judicious use of other antipseudomonal antimicrobials, which resulted in reduced resistance of P. aeruginosa to other b-lactams.
(Pharmacotherapy 2003;23(5):618-624)
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Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
(Pharmacotherapy 2003;23(5):625-637)
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Morbidity and mortality due to certain bacterial pathogens have not declined despite the availability of effective antimicrobial treatments. Staphylococcus aureus and Streptococcus pyogenes cause a number of serious infections, such as necrotizing fasciitis and toxic shock syndrome, which are associated with the release of bacterial toxins. Animal studies have demonstrated clindamycin, a protein synthesis inhibitor, to be more effective in treating these severe infections than other more susceptible antimicrobial treatments. Linezolid, another protein synthesis inhibitor, also has shown efficacy in in vitro studies. Human trials to validate the effects of antibiotic therapies on bacterial virulence have not been performed. Future animal and human studies are needed to help elucidate the immunomodulatory mechanisms of protein synthesis inhibitors in order to optimize antimicrobial treatment and decrease the morbidity and mortality associated with severe bacterial infections.
(Pharmacotherapy 2003;23(5):638-642)
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Objective. To determine the cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. An analysis was performed for subpopulations of patients receiving nephrotoxic agents (aminoglycosides, amphotericin, and acyclovir), those in the intensive care unit, and those on the oncology service.
Methods. Decision analysis was used to model the cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin. The reference case was determined, in part, by a retrospective review of 200 patients randomly selected from our clinical pharmacology consultation service. Patients were aged 18 years or older and had received intravenous vancomycin for at least 48 hours, with at least two -- one peak and one trough -- vancomycin serum concentrations obtained during therapy. Results of published clinical trials were used to determine the probability of vancomycin-induced nephrotoxicity.
Results. The mean cost of treating nephrotoxicity was $11,233 at our institution. The mean cost for all patients was $25,166 (sensitivity analysis $15,000-27,500)/nephrotoxic episode prevented. The subgroup analysis revealed a cost of $8363 (sensitivity analysis $4368-10,500)/nephrotoxic episode prevented in intensive care patients, $5000 (sensitivity analysis $1687-13,250) in oncology patients, and a dominant strategy showing a cost savings of $5564 (sensitivity analysis $2724-12,428) in those receiving concomitant nephrotoxins.
Conclusion. Although pharmacokinetic monitoring and dosage adjustment are effective methods for reducing the toxicity of many drugs, controversy exists regarding the necessity of such monitoring with vancomycin. Evaluation by decision analysis over a range of assumptions, varying probabilities, and costs reveals that pharmacokinetic monitoring and vancomycin dosage adjustment to prevent nephrotoxicity are not cost-effective for all patients. However, such dosage adjustment demonstrates cost-effectiveness for patients receiving concomitant nephrotoxins, intensive care patients, and probably oncology patients.
(Pharmacotherapy 2003;23(5):643-650)
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Study Objective. To determine prescribing patterns and clinical outcomes of enoxaparin for anticoagulation of atrial fibrillation.
Design. Retrospective analysis.
Setting. A 650-bed, tertiary care, community teaching hospital.
Subjects. Two hundred thirteen patients who received enoxaparin for thromboprophylaxis during an episode of atrial fibrillation.
Intervention. Data collection on demographics, antithrombotic usage, and thrombotic and bleeding episodes from January-June 2001.
Measurements and Main Results. Patients were characterized as having acute (51.6%) or chronic (48.4%) atrial fibrillation and were categorized according to stroke risk. Three enoxaparin dosing strategies had been prescribed: therapeutic, prophylactic, or adjusted. Prescribed regimens did not reflect stroke risk or type of atrial fibrillation but did reflect the degree of renal impairment. No episodes of stroke occurred with therapeutic enoxaparin dosages, but five strokes occurred among patients receiving prophylactic or adjusted dosages. Bleeding was similar with all dosing strategies in patients with adequate renal function and appeared to be more frequent in those with renal impairment.
Conclusion. At a single hospital, wide variation in enoxaparin prescribing patterns existed. Further study is necessary to elucidate more fully the appro-priate dosing strategy for this agent in the treatment of atrial fibrillation.
(Pharmacotherapy 2003;23(5):651-658)
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The level of compliance with clinical practice guidelines for patients with type 2 diabetes was evaluated in 368 patients from two health regions in rural northern Alberta, Canada. Data were collected from patient interviews, drug histories, physical and laboratory assessments, and a self-report questionnaire to assess clinical status, indicators of diabetes management, and health care utilization. Treatment of three clinical indicators of diabetes -- hemoglobin A1c (A1C), blood pressure, and low-density lipoprotein cholesterol (LDL) -- has been shown to reduce the morbidity and mortality associated with type 2 diabetes. Mean ± SD values for this cohort of patients were as follows: A1C 7.25% ± 1.54%, blood pressure 131.7 ± 18.2/76.2 ± 12.7 mm Hg, and LDL 105.2 ± 32 mg/dl. Despite these results, only 10.4% of the patients met all three recommended targets for control of glycemia: A1C below 7%, blood pressure below 130/85 mm Hg, and LDL below 100 mg/dl. Of patients not at target levels, 14.4%, 27.5%, and 86.7% reported receiving no therapy for hyperglycemia, hypertension, and dyslipidemia, respectively. Of those taking oral hypoglycemic agents who were not at target levels, only 35% were receiving combination therapy. Of patients at or above LDL target levels, 87% were not receiving any therapy. Only 22% of patients were taking aspirin, although this therapy would be recommended for the entire cohort according to clinical practice guidelines. Despite the availability of proved effective therapies, treatment gaps were present for this cohort of patients.
(Pharmacotherapy 2003;23(5):659-665)
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Study Objective. To examine community pharmacy practice with regard to providing smoking-cessation counseling.
Design. Mailed survey.
Setting. Iowa community pharmacies.
Participants. A stratified random sample of pharmacists statewide.
Measurements and Main Results. Descriptive statistics were computed for all study variables. Fisher exact test or x2 analysis was performed on selected variables to determine the relationship of each item with pharmacists routinely offering smokers suggestions for quitting. Responses from 129 (38.2%) of 338 pharmacists indicated that although most felt it is important to offer smoking-cessation counseling, about half actually offer this service. Most pharmacists indicated they are prepared to provide counseling, but fewer than 25% had received formal training or were aware of national clinical practice guidelines. Those who had received specific training (p=0.020) or recently attended an educational program (p=0.014) on smoking cessation were more likely to counsel smokers. Primary barriers to providing counseling were lack of time, inability to identify smokers, low patient demand, and lack of reimbursement.
Conclusion. Our findings suggest that opportunities exist for improving pharmacist education and reducing practice barriers in order to bridge the gap between pharmacists’ knowledge and attitudes related to smoking-cessation counseling and their provision of patient counseling in community pharmacy practice.
(Pharmacotherapy 2003;23(5):666-673)
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Purple toes syndrome is an extremely uncommon, nonhemorrhagic, cutaneous complication associated with warfarin therapy. It is characterized by the sudden appearance of bilateral, painful, purple lesions on the toes and sides of the feet that blanch with pressure. The syndrome usually develops 3-8 weeks after the start of warfarin therapy. A 47-year-old man with a history of purple toes syndrome that resolved after discontinuing warfarin -- prescribed for a deep vein thrombosis (DVT) in his right lower leg -- experienced an acute, proximal DVT in his other leg. Warfarin again was prescribed; 1 week later, purple toes syndrome developed in that extremity. Warfarin therapy again was discontinued, and intravenous unfractionated heparin was started; the patient’s clinical picture indicated a possible pulmonary embolism, and laboratory analysis suggested antiphospholipid syndrome. The patient’s toe pain resolved, but the purple discoloration persisted. Follow-up laboratory analysis confirmed antiphospholipid syndrome, and warfarin was restarted with close monitoring. No further complications occurred with long-term therapy. Although a rare complication of therapy, clinicians should monitor for the development of purple toes syndrome in patients taking warfarin.
(Pharmacotherapy 2003;23(5):674-677)
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Electric shock-like sensations may occur after cessation of treatment with serotonin selective reuptake inhibitors but are reported in the literature only rarely with discontinuation of venlafaxine. Two patients experienced severe shock-like sensations during venlafaxine withdrawal. For both patients symptoms occurred with lowering of the dosage and persisted for 5 days after complete discontinuation of the drug. These sensations may represent significant alteration of neuronal activity in the central nervous system.
(Pharmacotherapy 2003;23(5):678-681)
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With the increasing frequency of methicillin-resistant Staphylococcus aureus in immunocompromised hosts, clinicians are increasingly prescribing the oral treatment option of linezolid. Linezolid is the first of a new class of antibiotics, the oxazolidinones. The drug is generally well tolerated. However, mild-to-moderate adverse effects have been reported, such as gastrointestinal effects (most frequent), myelosuppression, skin eruptions, elevated liver enzymes, and tongue discoloration. As with any new drug on the commercial market, not all adverse effects are elucidated during preclinical trials. An immunocompromised 11-year-old girl with cellulitis of the toe experienced tooth discoloration after receiving a 28-day course of linezolid. The discoloration was present on the enamel of her lower anterior teeth and was superficial and reversible with dental cleaning.
(Pharmacotherapy 2003;23(5):682-685)
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The United Kingdom General Practice Research Database (GPRD) is an office-based, computer-generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.
(Pharmacotherapy 2003;23(5):686-689)
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In his recent article in Pharmacotherapy,1 Dr. Shane Scott estimated an epoetin alfa:darbepoetin alfa dose conversion ratio (DCR) by comparing week 0 epoetin alfa doses with week 24 darbepoetin alfa doses from several studies in which patients receiving hemodialysis were converted from epoetin alfa to darbepoetin alfa. Based on evidence in Table 1 and Figure 3 of his article (replicated as Table 1 and Figure 1),1 Dr. Scott concluded that the DCR is nonlinear and increases with epoetin alfa dose and that there is "large interpatient variability" in DCRs. He therefore recommended that no fixed DCR between epoetin alfa and darbepoetin alfa be used when converting patients from epoetin alfa to darbepoetin alfa. This recommendation contrasts with the Centers for Medicare and Medicaid Services (CMS) recent adoption of a fixed DCR of 260:1.2
(Pharmacotherapy 2003;23(5):690-694)
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