Interesting Articles in 2002 Jan - Mar
American Journal of Health-System Pharmacy
January 15, 2002 (Volume 59, Number 2)
Projecting Future Drug Expenditures
Shah ND, Vermeulen LC, Santell JP, Hunkler RJ, Hontz K
Am J Health-Syst Pharm. 2002;59:131-142
Medications account for a significant portion of pharmacy and total healthcare
costs. The ability to accurately predict expected expenditures has an impact on
the financial health of an organization. The authors of this article discuss the
factors driving increased drug expenditures and offer a forecast of future expenditure
patterns. Increases in drug expenditures are related to price inflation, utilization,
patient mix, and a blend of both of these factors. Data sources that are used
to help predict a forecast of pharmaceutical expenditure patterns include the
Producer Price Index (PPI), inflation rate projections, trends in expenditures
by practice settings, and hospital expenditure trends.
Drugs in development have a tremendous impact on the rise in pharmaceutical expenditures.
This article reviews drugs that were expected to receive approval in the last
part of 2001 and 2002. Legislative issues, generic drug approvals, and acts of
terrorism and their impact on drug expenditures are also addressed. The information
presented in the article can be used to help forecast expenditures for an individual
organization and must be coupled with data regarding local environment and organizational
characteristics that influence the use of medications.
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in Drug Expenditures Tied to More Prescriptions, Costlier Brand-Name Products
Take Bigger Slice of Total Health Care Expenditures
Increase in Drug Spending Largely Attributable to Few Costly Medications
Remain Focus of Cost-Containment Efforts
January 1, 2002 (Volume 59, Number 1)
Relationship Between Direct-to-Consumer Advertising and Physician Diagnosing
Zachry WM III, Shepherd MD, Hinich MJ, et al.
Am J Health-Syst Pharm. 2002;59:42-49
Retrospective data from 2 sources, the National Ambulatory Medical Care Survey
(NAMCS) and Competitive Media Reporting (CMR), were used for this study. The National
Center for Health Statistics is responsible for maintaining and administering
the NAMCS. Data are obtained from surveys of office-based physicians to identify
trends in prescribing and treatments. Data pertaining to advertising occurrence
and expenditures are collected by CMR and are intended for sale to researchers.
This study included products advertised for at least 19 months between January
1992 and July 1997. The initial sample of 19 specific agents was reduced for several
reasons, including the following: (1) identified agents comprised a drug class
so broad that associations among variables would be difficult, (2) the identified
drug was approved to change status from prescription only to nonprescription,
(3) the identified drug had multiple uses (both approved and off-label) associated
with multiple diagnosis, (4) the identified drug had disproportionately low advertising
expenditure, or (5) administration of the drug required surgical intervention.
The remaining 5 drug classes included antihistamines, antihypertensives, acid-peptic
disorder medications, benign prostatic hypertrophy medications, and antilipemics.
Quasi-experimental time-series techniques were used for the analyses and included
dependent variables (eg, monthly frequency of diagnosis for FDA-approved indications,
medications prescribed within a class, and medications prescribed for the specific
advertised agent) and independent variables (eg, monthly expenditures for advertising
each specific agent).
The amount of money spent advertising antihistamines was significantly associated
with the monthly number of prescriptions for Seldane (P < .001),
Claritin (P = .004), and Hismanal (P = .07). In addition,
the monthly number of prescriptions written for Zocor was significantly
associated with the advertising spending for antilipemics (P < .001).
Other significant associations were also noted.
As healthcare practitioners, we struggle with pharmaceutical advertising in general,
including direct-to-consumer (DTC) advertising. Although the authors point out
that causal relationships are not implied, this study suggests that increasing
spending on DTC advertising results in increased prescriptions written for some
pharmaceuticals. Whether or not DTC has a negative impact on the overall health
of the population is under debate. DTC advertising has made an impact on what
is prescribed, but the end result of the prescription and the impact on patient
outcome have not been determined.
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and State Laws and Regulations Affecting Managed Care
American Journal of Health-System Pharmacy
March 15, 2002 (Volume 59, Number 6)
Prevalence and Cost Savings of Therapeutic Interchange Among US Hospitals
Schachtner JM, Guharoy R, Medicis JJ, Newman N, Speizer R
American Journal of Health-System Pharmacy. 2002;59(6):529-533
Therapeutic interchange (TI) is often used as one method of cost-containment.
TI allows for the substitution of a less expensive, equally efficacious medication
for a more expensive medication within the same pharmacologic class. This survey
was conducted to obtain a detailed description of current TI practices and overall
cost impact of TI programs in US hospitals. Surveys were mailed to directors of
pharmacy; hospitals greater than 100 beds were targeted for the mailings. Surveys
were mailed in December of 1999.
A total of 463 surveys (29.8%) were returned. Both teaching (47%) and non-teaching
hospitals (53%) were represented. Close to 90% of all hospitals reported using
TI. The majority of hospitals did not require physician consent before a substitution.
Histamine h2-receptor antagonists, proton pump inhibitors, antacids,
first-generation cephalosporins, and quinolones were among the most common classes
of medications included in TI programs. Cost savings was estimated by 36% of teaching
hospitals, 38% of non-teaching hospitals, and 50% of investor-owned hospitals.
TI is a valuable tool for formulary management and cost containment purposes.
According to the results of the survey, most hospitals participate in some form
of TI program. TI is most effective when the guidelines for use are developed
using a multidisciplinary approach. Hospitals that use TI programs should periodically
review the programs to evaluate effectiveness and determine whether the guidelines
are being followed. Based on the results of quality improvement reviews, programs
should be modified to best suit the needs of the population being served.
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American Journal of Health-System Pharmacy
March 1, 2002 (Volume 59, Number 5)
Interdisciplinary Medication Education in a Church Environment
Schommer JC, Byers SR, Pape LL, Cable GL, Worley MM, Sherrin T
American Journal of Health-System Pharmacy. 2002;59(5):423-428
By some estimates, 120,000 lives and $45.6 billion could be saved each year in
the United States with successful medication education. Increased and improved
communication between patients and their health care practitioners is important
for improving patient knowledge, patient recall of directions, patient satisfaction,
and medication compliance. Based on this information, the investigators of this
study implemented and evaluated a medication education program for ambulatory
Patients were recruited from a base of 20 church congregations in the central
Ohio area. The study was designed to demonstrate the value and acceptance of medication
education provided in the church environment by an interdisciplinary team, reduce
unscheduled visits to health care providers attributed to improper medication
use, identify problems in medication use, increase patient awareness and understanding
of medication questions directed at health care providers, and increase patient
understanding of the role of the pharmacist.
Participants attended a 2-hour program that included an information session, a
one-on-one evaluation of medications with a pharmacist or pharmacy intern, and
an exit interview with a parish nurse. The parish nurse exit interview was used
to review the study questionnaires, answer questions, set-up follow-up appointments
as identified by the pharmacist, and ask the participant to complete a follow-up
survey in 6 months.
A total of 200 volunteers participated in the program. One hundred eighty-seven
of the 199 patients that agreed to participate in the follow-up survey were successfully
contacted at 6 months. Most patients (99.5%) reported that the church environment
was a good place to hold the program and that the program was valuable (> 90%).
Fourteen percent of the participants felt that the program was too lengthy. After
6 months, only 73% of respondents felt they had learned new medication-related
information compared with the 82% response rate obtained at the initial exit interview
(P < .05).
After participation in the program, patients took fewer daily medications (4.8
vs 5.5, P < .05). No significant differences in medical visits were
noted in the participants after the program. More patients asked questions about
their medications after participation in the program, and patients reported feeling
more comfortable asking questions after the program (P < .05).
Appropriate medication use is important to the overall usefulness of prescribed
medication regimens. Patients must be empowered to understand their medications
and the need to be comfortable discussing medications with their health care practitioners.
The reality of today's medical system limits the availability of any one practitioner
to thoroughly educate patients about their medications. Many patients seek avenues
to self-learn medication information. Programs that are provided by health care
practitioners to deliver education to patients are often well received.
Many patients do not have the financial means to pay for educational programs.
This means that these programs must either be provided at no charge or subsidized
by the government or health care providers. The onus is on the medical professional
to search for ways to provide programs that are not associated with high costs.
The use of facilities such as senior centers, community centers, and churches
where the cost for space may be minimal is a good way to find ways to offer educational
services at a low cost. The ability of a program participant to feel at ease and
comfortable during the interview is an important factor that has too often been
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The Annals of Pharmacotherapy
February 2002 (Volume 36, Number 2)
Influence of Standardized Orders on Postoperative Nausea and Vomiting After
St. Pierre E, Frighetto L, Marra CA
The Annals of Pharmacotherapy. 2002;36(2):210-217
Postoperative nausea and vomiting (PONV) occurs in over 50% of patients who undergo
gynecologic surgery. Other studies have demonstrated better efficacy in patients
who receive prophylactic antiemetics rather than using a rescue approach once
the nausea and vomiting has begun. One large tertiary care teaching hospital developed
standardized presurgical orders forms for PONV prophylaxis. Once implemented,
this retrospective study was conducted to evaluate the effectiveness of the preprinted
Patients who had undergone gynecologic surgery over a 6-month period before implementation
of the standard order forms and similar patients from a 6-month period after implementation
served as the study group. There were 400 patient records included in the analysis;
200 in each group. The proportion of patients who experienced PONV decreased after
implementation, 77% (pre) vs 68% (post), P = .04. Prophylactic antiemetics
were administered in 47% of cases (post) vs 31% (pre), P = .002. Metoclopramide
was the most commonly used antiemetic agent. No significant adverse events due
to use of antiemetic agents were noted.
In this study, patients in the preimplementation group had longer surgeries than
patients included in the postimplementation group (P = .09) which could
have skewed the results. Still, the improvements observed were significant. Because
PONV can have an impact on the cost of a surgical procedure, due to increased
complications and longer stays, this approach to standardizing the use of prophylactic
antiemetic agents is worth considering.
Journal of Managed Care Pharmacy
January/February 2002 (Volume 8, Number 1)
Effect of Physician Profiles and Academic Detailing on Cost and Utilization
of Selective Serotonin Reuptake Inhibitors
Yokoyama KK, Doan QD, Godley PJ, et al.
Journal of Managed Care Pharmacy. 2002;8(1):23-31
Physician profiling has been used as a means of providing feedback to clinicians
regarding their use of prescription medications, utilization of clinical procedures
and laboratory tests, office visits, hospital admissions, and referrals to specialists.
This study evaluates the use of physician profiling and periodic education in
a staff-model managed care organization on the cost and utilization of selective
serotonin reuptake inhibitors (SSRIs).
Family practice and internal medicine providers associated with this 168,500 member
managed care organization were targeted for the intervention. Beginning with year
3 of the study, physicians received a quarterly profile that included information
about their use of SSRIs (postintervention phase). In addition to these reports,
academic detailing was provided at 13 of the largest regional clinics. Attendance
at the group educational sessions was not mandatory but was strongly encouraged.
Interventions were targeted at encouraging physicians to consider "non-fluoxetine"
SSRIs as the cost to the plan for these medications was less. Pharmacy claims
data for the 4-year study period was used to determine utilization.
Over the 4-year period, the per-member-per-month (PMPM) days of therapy rose from
0.535 days PMPM in 1997 to 0.763 days PMPM in 2000. The utilization of SSRIs other
than fluoxetine rose from 53.8% to 68%. The cost of SSRI therapy per day declined
from $2.43 in 1998 to $2.16 in 2000.
The use of physician profiles has not been universally successful at altering
physician-prescribing behavior. In this study, the use of profiles was combined
with additional academic detailing. Perhaps more education, whether written or
verbal, along with the physician profile enhances acceptance and more successfully
February 2002 (Volume 22, Number 2)
Pharmacist Impact on Posttraumatic Seizure Prophylaxis in Patients With Head
Brophy GM, Tesoro EP, Schrote GL, Garnett WR
High-risk head injury patients often receive posttraumatic seizure prophylaxis
with carbamazepine or phenytoin. Currently, 7 days of therapy is the recommended
length of prophylactic treatment. Many patients receive therapy that falls outside
this duration. Signs of toxicity or seizure activity may be difficulty to detect
in this population, because of their medical condition. In patients receiving
phenytoin, keeping trough concentrations at the desired level is a goal of therapy.
This study evaluated the impact of a pharmacist on posttraumatic seizure prophylaxis
in head trauma patients admitted to a neuroscience intensive care unit. The impact
of the pharmacist's involvement on phenytoin dosing and monitoring, cost avoidance,
and patient outcome was measured.
Data were collected from patients admitted to the unit over 2 time periods, before
a pharmacist routinely participated in the care and monitoring of patients (BP)
and after the pharmacists became an active member of the patient care team (AP).
Data from 43 patients in the BP group and 66 patients in the AP group were included
in the analysis. Patients in the BP group received an average of 13.4 days of
phenytoin, whereas patients in the AP group received an average of 7.6 days of
treatment. A difference in the average number of phenytoin concentrations measured
also differed between the two groups; an average of 10.3 phenytoin levels were
collected in the BP group compared with 3.4 in the AP group. Fifty-eight percent
of appropriately drawn levels were in the target range in the AP patients compared
with 28% in the BP group. Seizures occurred in 4.7% of the BP group and 1.5% of
the AP group. The decrease in the number of phenytoin concentrations measured
in the AP group translated to a cost savings of approximately $19, 000. A switch
to oral therapy in 86% of AP patients was associated with a cost savings of approximately
The presence of a pharmacist on a critical care unit adds continuity to the care
of a patient. Oftentimes, the impact of the pharmacist comes from subtle activities,
such as monitoring a patient's therapy for appropriate dose, duration, and route
of administration. Because of the complexity of critical care patients, prophylactic
therapies may fall through the cracks. In this study, the pharmacist was able
to successfully impact cost by carefully monitoring posttraumatic seizure prophylaxis.
Journal of Clinical Pharmacology
January 2002 (Volume 42, Number 1)
Pharmacodynamics and Safety of a New Calcium Sensitizer, Levosimendan, and
Its Metabolites During an Extended Infusion in Patients With Severe Heart Failure
Kivikko M, Antila S, Eha J, Lehtonen L, Pentikainen PJ
Journal of Clinical Pharmacology. 2002;42(1):43-51
Levosimendan, through its calcium-dependent binding to cardiac troponin C, exerts
a positive inotropic effect on the myocardium. It also induces vasodilation by
acting as an opener of ATP-dependent K-channels in vascular smooth muscle. Levosimendan
itself has a short half-life, approximately 1 hour. Active metabolites of levosimendan
that have longer half-lives have been identified. This study was undertaken to
assess the pharmacodynamic effects and safety of levosimendan when administered
by continuous intravenous infusion over a 7-day period.
A total of 24 patients with New York Heart Association (NYHA) III-IV heart failure
and an ejection fraction < 40% were included in this open-label, nonrandomized
phase 2 study. Patients were divided into 2 groups for dosing of levosimendan.
One group (n = 12) received levosimendan at 0.05 mcg/kg/min for the 7-day period;
the other group (n = 12) received levosimendan at 0.1 mcg/kg/min for the study
period. Patients were followed up for 10-15 days following dosing.
Eight patients in each group reported adverse events. With one exception, the
adverse events were considered mild to moderate and included rhythm disorders,
infusion-site reactions, headache, hypotension, rash, swelling in the lower extremities,
angina, and dizziness. One patient experienced worsening heart failure 10 days
after stopping the levosimendan; this was considered unrelated to treatment.
Mean heart rate increased significantly from baseline in both treatment groups
(P < .001); the increase was 18 beats per minute (BPM) in the low-dose
group and 26 BPM in the high-dose group. The effects slowly decreased from a peak
at the end of the treatment period throughout follow-up. The elimination half-life
of levosimendan was 1 hour throughout the infusion period. The half-lives of the
metabolites measured were between 70 and 80 hours.
Levosimendan represents a new class of therapeutic agents -- the calcium sensitizers
-- for treating heart failure. With active metabolites that are not rapidly cleared
from the body, it is important to determine if toxicity will limit the duration
of levosimendan infusion that a patient will tolerate. This study suggests that
at least at the doses used, it is tolerated for a duration of 7 days. Of interest,
the effects of levosimendan infusion decreased slowly over the follow-up period.
This prolonged effect is probably also due to the long half-lives of the active
International Journal of Clinical Pharmacology and
February 2002 (Volume 40, Number 2)
Comparison of Different Reduced Sampling Approaches for the Estimation of
Pharmacokinetic Parameters for Long Half-Life Drugs in Patients With Renal or
International Journal of Clinical Pharmacology and Therapeutics. 2002;40(2):53-59
Estimating pharmacokinetic parameters in patients with renal or hepatic impairment
can be difficult and can require multiple plasma samplings over many days. Reduced
sampling schemes (48 or 72 hours) may provide adequate information on which to
base dosing decisions. This study evaluated 3 different reduced sampling schemes
(Bayesian, population analysis, and the truncated area method) to determine half-life,
clearance, and Cmax of 2 different drugs. Both drugs used in the study had a half-life
of at least 30 hours.
In the first 2 groups, 18 patients received a single dose of Drug A. Drug A is
hepatically cleared. Nine of the 18 patients were healthy and 9 had alcoholic
cirrhosis. Blood samples were drawn over 120 hours. A second drug, renally cleared
Drug B, was given as a single dose to 7 patients in each of 4 groups. Patient
assignment to a treatment group was by creatinine clearance. Blood samples in
these patients were drawn over 168 hours.
Using only the reduced sampling method, the Bayesian and population analysis schemes
provided similar pharmacokinetic parameters to the values obtained when the extended
sampling times were used. The truncated area method did not accurately characterize
the pharmacokinetics of long-half-life drugs in patients with renal or hepatic
Many patients have complicated medication regimens that are further complicated
by disease states that alter the pharmacokinetic parameters of their therapy.
Understanding the limitations of different methods of estimating pharmacokinetic
parameters is important to clinicians attempting to dose therapy safely and effectively
while minimizing the number of sampling points.
Clinical Pharmacology and Therapeutics
January 2002 (Volume 71, Number 1)
Pharmacokinetics of Betamethasone in Twin and Singleton Pregnancy
Ballabh P, Lo ES, Kumari J, et al.
Clinical Pharmacology and Therapeutics. 2002;71(1):39-45
This study was designed to compare the pharmacokinetics of betamethasone in twin
and singleton pregnancy. Serial betamethasone levels were measured in 51 patients
-- 30 singleton and 21 twin pregnancies. In a subset of these patients, cord and
maternal blood levels of betamethasone at birth were measured.
Half-life was significantly shorter in the twin pregnancies: 7.2 +/- 2.4 hours
vs 9.0 +/- 2.7 hours (P < .017). Clearance was increased in twin pregnancies:
8.4 +/- 6.4 L/hr vs 5.7 +/- 3.1 L/h (P < .06). Volume of distribution
was not affected. Mothers with a longer lag time between the last dose of betamethasone
and delivery had higher cord and maternal ratios compared with mothers with a
shorter time span between dosing and delivery.
This small study offers important pharmacokinetic data regarding betamethasone
in twin pregnancies. The increased clearance and shorter half-life of betamethasone
in this patient population may necessitate a change in dosing for women with twin
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Clinical Drug Investigation
February 2002 (Volume 22, Number 2)
Bioavailability of Budesonide Delivered by the Clickhaler and Turbuhaler
Dry Powder Inhalers in Healthy Volunteers: A Pilot Study
Godfrey C, Buck H, Ellis S
Clinical Drug Investigation. 2002;22(2):119-124
The pharmacokinetic profile and bioavailability of 1000-mcg budesonide following
dry powder inhalation from the Clickhaler and Turbuhaler were compared
in this randomized, double-blind, double-dummy crossover study. Six healthy males
aged 19-44 years were enrolled in the study. A washout period of 3-7 days was
used between study periods. Following inhalations of budesonide, serial blood
samples were collected to determine plasma levels of budesonide and cortisol.
The 8-hour mean AUC values for the Clickhaler and Turbuhaler dosing
were similar. Plasma budesonide time profiles and plasma cortisol concentration-time
profiles were also similar. No significant adverse effects were associated with
either budesonide formulation.
This small study of budesonide administered via 2 different formulations indicates
that the formulations offer similar bioavailability. The study was conducted in
a very small group of healthy males and will need to be repeated in a larger group
of patients with asthma. If the similarities in bioavailability and systemic activity
remain similar, this information can be used to make formulary and therapeutic
American Journal of Health-System Pharmacy
February 1, 2002 (Volume 59, Number 3)
Implications of Prion-Induced Diseases for Animal-Derived Pharmaceutical Products
American Journal of Health-System Pharmacy. 2002;59(3):254-263
Prion-induced disease, bovine spongiform encephalopathy (BSE), is known as "mad
cow disease" in the media. Prions are particles that contain proteins but no nucleic
acid; prions are found in both humans and animals. Not all forms of prions are
pathogenic. Because medications derived from plasma fractionation could theoretically
be contaminated with infectious prions, the article discusses the potential for
The article offers a review of transmissible spongiform encephalopathies, the
clinical appearance, diagnosis, and natural course of the new variant Creutzfeldt-Jakob
disease (CJD); transmission, surveillance, and treatment of CJD; infection control
measures aimed at limiting the transmission of prion-induced diseases; and advice
for patients concerned about mad cow disease. According to this review, no reported
human cases of new-variant CJD from bovine-derived products have been reported.
In addition, no well-documented evidence exists that links the use of blood or
blood products to the transmission of CJD. While no links exist between prion-induced
diseases in humans secondary to medications developed from plasma fractionation,
continued surveillance and investigations will continue.
This review offers important insight into prion-induced diseases. The author supplies
important information that should be reviewed by healthcare practitioners so that
they remain well informed and can supply this information to concerned patients.
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The Annals of Pharmacotherapy
January 2002 (Volume 36, Number 1)
Correlation Between Activated Clotting Time and Activated Partial Thromboplastin
Smythe MA, Koerber JM, Nowak SN, et al.
The Annals of Pharmacotherapy. 2002;36(1):7-11
Data from previous work on the monitoring of unfractionated heparin was reviewed
retrospectively to achieve the objectives of this study. Those objectives included
determining the correlation between plasma heparin concentration and clotting-time
tests and between activated clotting time (ACT) and activated partial thromboplastin
time (aPTT) as well as comparing heparin dose adjustment decisions based on ACT
with those based on aPTT.
Data from 100 patients were used to establish the correlation between ACT and
heparin concentration, 0.72. Bedside and laboratory aPTTs were used in the original
study and thus comparison of aPTT and heparin concentration yielded a range of
correlation values, depending on the instrument used, 0.74 to 0.86, with the highest
correlation associated with the laboratory aPTT. Correlation of the aPTT and the
ACT results yielded a correlation of 0.64 to 0.67. Heparin dosing adjustments
made using ACT results were different from decisions arrived at using aPTT results
37% to 41% of the time.
Although the controversy about the best way to monitor and adjust heparin therapy
is not new, it is worth reviewing again. Despite the existence of national guidelines
that can guide heparin dosing conditions, it is important that clinicians recognize
the limitations of the clotting-time test employed at their unique institution.
This study demonstrates that heparin dosing decisions differed when different
clotting-time tests were used.
Journal of the American Pharmaceutical Association
January/February 2002 (Volume 42, Number 1)
Results of a Smoking Cessation Clinic in Community Pharmacy Practice
Kennedy DT, Giles JT, Chang ZG, Small RE, Edwards JH
Journal of the American Pharmaceutical Association. 2002;42(1):51-56
Most healthcare practitioners recognize the hazards of smoking and its implications
with regard to patients' health. Despite this knowledge, many clinicians are reluctant
to speak to patients about smoking cessation. Pharmacists in community practice
are positioned to promote smoking cessation. In this study, results from a demonstration
project in chain pharmacies are analyzed.
Pharmacists and fourth-year doctor of pharmacy students were trained both on-site
and at off-site locations on the transtheoretical model for change as applied
to smoking cessation, charting, behavioral modification techniques, stages of
change as applied to smokers, nonprescription and prescription smoking cessation
therapies, and patient counseling. Patients serviced at the participating pharmacies
were asked if they smoked and whether they would like to quit. Patients could
also enter the program by referral from physicians or nurses. An addiction scale
score was used to determine a smoker's level of nicotine dependence (6-10 = high
level of dependence, < 6 = low level of dependence).
Patients were followed for a 1-year period from the agreed-upon quit date. A total
of 48 patients were recruited for participation. Twenty-five percent of these
patients abstained form smoking for 12 months or more. These patients had a mean
addiction score of 4.2. Smoking cessation rate correlated with sex (F > M)
but not with age, number of cigarettes smoked per day, level of nicotine dependence,
previous cessation attempts, or method of cessation. Patient satisfaction surveys
indicated a high level of satisfaction with the service.
As with many patient care activities, it is easy to see how influential the community
pharmacist can be in helping a patient achieve positive therapy outcomes. However,
the reality of time constraints and lack of reimbursement for activities such
as this will prohibit widespread incorporation into daily activities. Recognition
of the value of these services outside of the pharmacy community is limited. Reports
of successes like this must be shared with administrators and other healthcare
January 2002 (Volume 22, Number 1)
Comparison of Risperidone With Olanzapine in Elderly Patients With Dementia
Ellingrod VL, Schultz SK, Ekstam-Smith K, Kutscher E, Turvey C, Arndt S
Antipsychotic agents are primarily used in the elderly for the treating treatment
of psychosis associated with dementia. Typical antipsychotics have a high frequency
of drug-induced side effects, leading to increased use of the atypical antipsychotic
agents as first-line therapies in this age group. In this study, the effects of
risperidone and olanzapine on cognition were compared. Drug-induced side effects
in elderly patients were also recorded. The Mattis Dementia Rating Scale was used
to measure cognition.
Patients aged >/= 70 years with a diagnosis of Alzheimer-type dementia, multi-infarct
dementia, or mixed syndrome and receiving an antipsychotic medication were recruited
from 4 rural nursing care facilities. Following a baseline assessment, patients
were treated with either risperidone or olanzapine in the single-blind, nonrandomized
study. Primary care physicians determined individual patient dosages. Risperidone
doses ranged from 0.25 mg/day to 3 mg/day. Olanzapine dosages ranged from 2.5
mg/day to 15 mg/day. A single clinician assessed patients at baseline, 1 month,
and 2 months. The clinician, the patient, and the family were blinded to the treatment
A total of 19 patients were enrolled in the study. Eleven patients received risperidone
and 8 patients received olanzapine. Social-Adaptive Functioning Evaluation increased
in all patients (P = .03). No significant difference in the score was noted
between groups. Scores on the Mattis Scale and Mini-Mental State Examination declined
in patients receiving risperidone compared with baseline (P < .05).
A significant increase in Simpson-Angus Extrapyramidal Symptoms scores occurred
in the olanzapine group compared with baseline (P < .05). Blood pressure
also decreased in the olanzapine group compared with baseline (P < .07).
A significant difference between groups did not occur with any of the measurements.
This small study offers an important contribution to the published literature.
The incidence of dementia in the elderly and the need to treat psychosis associated
with the disease continue to rise. It is interesting to note that no change was
observed on the psychosis rating scales during this study, despite improvements
in social functioning. Larger groups of patients will need to be studied to determine
whether certain patient groups are more apt to suffer adversely from these treatments
and whether a difference in response to these agents exists.
British Journal of Clinical Pharmacology
February 2002 (Volume 53, Number 2)
The Effects of Rifampicin on the Pharmacokinetics and Pharmacodynamics of
Orally Administered Nilvadipine to Healthy Subjects
Saima S, Furuie K, Yoshimoto H, Fukuda J, Hayashi T, Echizen H
British Journal of Clinical Pharmacology. 2002;53(2):203-206
The oral bioavailability of calcium channel blockers can be decreased by concomitant
administration with rifampicin. The interaction occurs because rifampicin is metabolized
through the cytochrome p450 enzyme system. An interaction between nifedipine and
rifampicin has been established. Nilvadipine is a second-generation calcium channel
antagonist used in the treatment of hypertension. Because it is closely related
to nifedipine, a drug interaction with rifampicin was expected. This study used
5 healthy volunteers to determine whether coadminstration of rifampicin and nilvadipine
resulted in altered pharmacokinetic and pharmacodynamic effects.
All study subjects were considered healthy and were not taking any medications
other than study drugs. Pharmacokinetic and cardiovascular effects of nilvadipine
were studied prior to the initiation of rifampicin and after a 6-day course of
concomitant rifampicin. Serial blood samples were collected and used for pharmacokinetic
measurements. Blood pressure was assessed using a sphygmomanometer. Supine and
standing blood pressures were assessed at baseline and 1 hour following an oral
dose of nilvadipine.
The AUC of nilvadipine was lower following concomitant dosing with rifampicin.
The mean AUC of nilvadipine before rifampicin treatment was approximately 30 times
greater than the mean AUC following rifampicin administration (P < .05).
The mean peak plasma concentration of nilvadipine was approximately 20 times greater
before treatment with rifampicin (P < .05). When nilvadipine was administered
alone, a significant decrease in diastolic pressure and an increase in heart rate
were observed. These effects were not noted with the coadministration of rifampicin
The results of this small drug interaction study suggest that the coadministration
of nilvadipine and rifampicin results in a loss of nilvadipine's therapeutic effect.
Although the drug is not currently available in the United States, clinicians
in countries where nilvadipine is available should be aware of this drug interaction.
When the interaction cannot be avoided, an increase in nilvadipine dose may be
British Journal of Clinical Pharmacology
January 2002 (Volume 53, Number 1)
Distribution of Venlafaxine and Its O-Desmethyl Metabolite in Human
Milk and Their Effects in Breastfed Infants
Ilett KF, Kristensen JH, Hackett LP, Paech M, Kohan R, Rampono J
British Journal of Clinical Pharmacology. 2002;53(1):17-22
Venlafaxine is a bicyclic phenylethylamine antidepressant that inhibits serotonin
and norepinephrine reuptake. Following delivery, some women develop postpartum
depression that may require treatment with an antidepressant medication. This
study was designed to determine the transfer of venlafaxine and 0-desmethyl
venlafaxine into the breast milk of lactating women. 0-desmethyl venlafaxine
has activity that is similar to that of venlafaxine. Plasma concentrations and
effects in the breast-fed infants were reviewed.
Six lactating women and their infants participated in the study. The mean age
of the infants was 7 months. Following an oral dose of venlafaxine, serial blood
and breast milk samples were collected from the mothers. Infant blood samples
were collected at a mean of 6.5 hours following maternal dosing. Venlafaxine was
detected in only 1 infant sample at a low concentration. 0-desmethyl venlafaxine
was detected in 4 of the 6 infants; concentrations ranged from 3 mcg/L to 38 mcg/L.
None of the infants experienced adverse effects.
The risk vs benefit of any agent used in lactating women needs to be assessed
prior to exposure of the infant to the agent. The exposure of the infants to venlafaxine
and its active metabolite was relatively low in this study. In many cases, when
the risk of adverse effects is low, treating the mother with medication and encouraging
breastfeeding will benefit both the baby and the mother.
January 2002 (Volume 24, Number 1)
Combination Hydrocodone and Ibuprofen Versus Combination Oxycodone and Acetaminophen
in the Treatment of Moderate or Severe Acute Low Back Pain
Palangio M, Morris E, Doyle RT Jr, Dornseif BE, Valente TJ
Clinical Therapeutics. 2002;24(1):87-99
This randomized, double-blind, parallel-group, repeat-dose study compared the
efficacy and tolerability of combination hydrocodone 7.5 mg and ibuprofen 200
mg (HC/IB) with combination oxycodone 5 mg and acetaminophen 325 mg (OC/AC). Adult
patients with a diagnosis of acute low back pain requiring opioid or opioid-nonopioid
combination therapy were eligible for the study. Patients were admitted to the
study within 48 hours of the onset of pain and completed a baseline self-assessment
pain intensity rating. Patients were treated on an outpatient basis. All study
participants were required to complete 2 visits within an 8-day period. Day 1
was considered baseline, and day 8 or day of treatment discontinuation was considered
the study end point. Patients kept a daily diary and recorded end of day pain
relief, number of tablets and doses of supplemental analgesic medications taken,
and type and frequency of any prescribed physical therapy. At the end point of
the study, patients were asked to make a global assessment of their treatment
(poor, fair, good, very good, excellent). A physical examination and Short-Form
Health Survey (SF-36) were also completed at the end point.
Patients were randomized; the recommended starting dosage for both treatments
was 1 tablet every 4 to 6 hours with a maximum of 5 single tablets per day. Up
to 4 daily doses of supplemental analgesic medicine (ibuprofen 200 mg for patients
receiving HC/IB and acetaminophen 325 mg for patients receiving OC/AC) were allowed
during the study period. No more than 1 supplemental dose of analgesic was allowed
between 2 doses of study medication. No other analgesic or anti-inflammatory medications
A total of 147 patients entered the study. Sixty-four of 75 HC/IB patients and
61 of 72 OC/AC patients completed the study. Reasons for discontinuation were
similar between the two groups and included adverse events, recovery, lack of
efficacy, loss to follow-up, and protocol violation. Mean daily pain relief scores
improved in both groups from baseline to end point measurement (P <
.001). Measurement of efficacy was similar in both groups. Mean daily pain relief
scores, mean daily number of tablets and doses of study medication, mean daily
doses and tablets of supplemental analgesic medication, and global assessments
were similar in both sets of patients. Adverse events were similar for both treatments.
The results of this study indicate that the two combination analgesic preparations
have comparable efficacy. Larger controlled trials will need to be conducted to
determine whether the combination product that contains an anti-inflammatory agent
is the better product for acute lower back pain.
Journal of Clinical Pharmacology
February 2002 (Volume 42, Number 2)
Multiple-Dose, Linear, Dose-Proportional Pharmacokinetics of Retigabine in
Ferron GM, Paul J, Fruncillo R, et al.
Journal of Clinical Pharmacology. 2002;42(2):175-182
Retigabine is a selective M-current potassium channel opener for the KCNQ2/3 and
KCNQ3/5 channels under investigation as an antiepileptic agent. This is the first
agent in this class of drugs to undergo investigation. Retigabine exerts its activity
by opening potassium channels and by potentiating gamma amino butyric acid (GABA).
Mutations in KCNQ2/3 and KCNQ3/5 potassium channels have been linked to benign
neonatal familial convulsions. Retigabine is being investigated as an antiepileptic
agent in the treatment of partial and generalized onset seizures. This study was
conducted in 45 healthy adult male volunteers to assess the pharmacokinetics of
retigabine and its partially active metabolite, AWD21-360. Assessment was conducted
following single and multiple doses of oral retigabine. Safety and tolerability
were assessed using a fixed dose and a dose titration schedule.
Study patients participated in only 1 dose group in this double-blind, placebo-controlled,
ascending-dose, dose-escalating study. Nine patients were evaluated at each dose
level; 6 patients received active study drug and 3 received placebo. Retigabine
was dosed at 100, 200, 250, or 300 mg every 12 hours for 15 days. With the exception
of the dose titration group, each subject received the same dose level each day.
The titration group was started on a dose of 200 mg and increased by 100 mg every
4 days to achieve a 700-mg/day dose on day 15. Study drugs were administered with
250 mL of tap water. Subjects reported to the study center on the day before the
first dose and stayed through the morning of day 17. Serial blood samples were
collected on days 1 through 15. Physical exams, clinical laboratory values, electrocardiogram
reading, vital sign measurements, and spontaneous reports of adverse events were
used to assess safety.
Pharmacokinetic parameters were similar throughout the study period. The accumulation
ratio with multiple dosing was 1.5. Retigabine was rapidly absorbed and maximum
concentrations were reached within 1.5 hours of dosing. The mean terminal half-life
was approximately 8 hours; oral clearance was 0.7 L/h/kg in white study patients.
Clearance was reduced by 25% in black study patients. Over the range of 100 to
700 mg of retigabine, the pharmacokinetics were linearly dose proportional. Dose-limiting
adverse effects were evident in the fixed-dose regimen at 600 mg/day. These patients
complained of chills, pain, symptomatic hypotension, dizziness, nausea, myalgia,
sweating, and vomiting. Titration allowed for higher doses compared with the fixed-dose
This pharmacokinetic study offers some insight into the challenges that might
face clinicians should this medication become available in the United States.
The need for titration with any medication often leads to compliance problems.
In addition, significant differences in clearance between races may lead to over-
or under-dosing in some patients.
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