Literature Highlight Risk of Major Congenital Malformations After by t0231232


									                                       DIS News
            Co l l e g e o f H e a l t h P ro f e s s i o n s a n d B i o m e d i c a l S c i e n c e s
                                   D ru g I n fo r m a t i o n S e r v i c e
                                            Literature Highlight:
 Risk of Major Congenital Malformations After First-Trimester Exposure to ACE
Angiotensin converting enzyme (ACE) in-          terval (CI) 1.72-4.27) in infants exposed to an
hibitors are safe and effective for the treat-   ACE inhibitor. Furthermore, the relative risk of       July 2006
ment of hypertension; however, they are con-     cardiovascular malformations and central nerv-
traindicated during the second and third tri-    ous system malformations was 3.72 (95% CI
mester of pregnancy. First trimester expo-       1.89-7.30) and 4.39 (95% CI 1.37-14.02), re-           Volume 10, Issue 7
sures to ACE inhibitors have not demon-          spectively. There was no increased risk of mal-
strated adverse fetal outcomes, although there   formations in infants exposed to other antihyper-
are some reports of malformations. To clar-      tensive medications compared to controls. Con-
                                                                                                        Inside this issue:
ify the safety of ACE inhibitors in the first    founding factors such as the severity of hyper-
trimester of pregnancy, a large retrospective    tension and the use of other medications cannot        Chantix®                2
cohort study was performed using the Ten-        be ruled out.
nessee Medicaid database to evaluate the as-                                                            Literature High-     3
sociation between congenital malformations       Summary: Exposure to ACE inhibitors during             light: Fluoxetine in
and exposure to ACE inhibitors during the        the first trimester significantly increases the risk   patients with ano-
first trimester of pregnancy.                    of congenital malformations. Therefore, ACE            rexia nervosa
                                                 inhibitors should be avoided during the first tri-
A chart review from 1985 to 2000 identified      mester of pregnancy and throughout gestation.
29,507 eligible infants. The primary study
endpoint was the number of congenital mal-
formations in infants exposed to ACE inhibi-     Cooper WO, Hernandez-Diaz S, Arbogast PG, et
tors or other antihypertensives compared to a    al. Major congenital malformations after first-
non-exposed control group. Pharmacy fill         trimester exposure to ACE inhibitors. N Engl J
data was used to identify infants exposed to     Med 2006;354(23):2443-2451.
ACE inhibitors during the first trimester.
Exclusion criteria included maternal diabetes,
ACE inhibitor exposure after the first trimes-
ter, and exposure to other potential terato-     By Kyle Austin, Pharm. D. Candidate
gens. Malformations were defined using
definitions from the Centers for Disease Con-
trol and Prevention and were identified using
                                                                                                          We welcome any com-
ICD-9-CM codes.                                                                                          ments or suggestions for
                                                                                                         future newsletter topics.
Records revealed 209 infants exposed to ACE
inhibitors during the first trimester, 202 in-
fants exposed to other antihypertensive medi-
cations, and 29,096 infants with no exposure                                                                 Editors in Chief
to antihypertensive medications. Congenital                                                                Genine Thormahlen,
malformations occurred in 18 (7.12%) infants                                                                    Pharm. D.
exposed to an ACE inhibitor during the first
                                                                                                          Sherrill Brown, DVM,
trimester compared to 4 (1.73%) exposed to
other antihypertensive medications and 834                                                                      Pharm. D.
(2.63%) with no antihypertensive medication
exposure. The relative risk of any congenital
malformation was 2.71 (95% confidence in-
Chantix® (varenicline): Novel Treatment for Smoking Cessation
      Tobacco use remains the largest         onstrated a greater short-term and long-     dreams (13%), asthenia (7%), taste
preventable cause of death and disease,       term response rate than those receiving      perversion (5%), respiratory tract in-
with cancer, cardiovascular diseases, and     bupropion SR. Varenicline had a re-          fection (5%), and rash (3%).2
respiratory diseases among its many           sponse rate for continuous abstinence of           Additional data from the manufac-
serious adverse effects. An estimated         22.5% at weeks 9-52, compared to a           turer (Monge T, Medical Information
1.2 billion people worldwide use to-          15.7% response rate for bupropion SR         Specialist, Pfizer, personal communi-
bacco. While smoking prevalence falls         and 9.4% for placebo (p<0.0001). Over-       cation, May 19, 2006) indicates that
slowly toward 20% in some Western             all discontinuations from treatment due      the overall incidence of adverse events
countries, tobacco use remains high in        to adverse events were lower with            ranged from 81% - 90% of the subjects
many developing countries and is greater      varenicline than with bupropion SR and       receiving varenicline in one study;
than 50% among men in many Asian              similar to placebo in both studies. The      however, the adverse events occurred
countries. In the United States, 30-50%       third study with a comparative bu-           less commonly in those receiving a
of tobacco users attempt to quit each         propion SR arm, also 12 weeks long,          titrated varenicline regimen (either 0.5
year. Long-term tobacco abstinence            found that varenicline was consistently      mg daily for seven days followed by
rates remain less than 30%, however,          associated with a higher smoking quit        0.5 mg twice daily for 11 weeks or 0.5
despite a number of moderately effective      rate than bupropion SR (p<0.05). The         mg daily for three days followed by
pharmacological treatments for tobacco        study also found that varenicline 1 mg       0.5 mg twice daily for four days, then
dependence.1                                  daily and 1 mg twice daily were the most     1 mg twice daily for 11 weeks). In
      Chantix® (varenicline) is a prescrip-   effective doses (p<0.001). Varenicline       addition, a 52-week study evaluating
tion oral drug that was approved by the       was found to be effective in eliminating     the long-term safety of varenicline in
FDA in May 2006 as an aid to smoking          the reward sensations associated with        251 subjects reported no adverse
cessation treatment.2 The development         smoking: smoking satisfaction, psycho-       events relative to serum chemistry pan-
of varenicline started in the 1960s in the    logical reward, enjoyment of respiratory     els, hematology, or ECG parameters.
Soviet Union. It has been available           tract sensations, and craving reduction      No deaths occurred during the study,
commercially in Bulgaria and on the           upon smoking. It did not, however, dif-      and serious adverse events (not de-
internet under the trade name Tabex®          fer significantly from placebo with re-      scribed) were reported in 15 subjects
(manufactured by Sopharma) and has            gards to aversion.                           receiving varenicline and 3 subjects
been generally well-tolerated without              Patients wanting to quit smoking        receiving placebo.
many side effects.1 Varenicline binds         should set a quit date, and treatment with         Varenicline is described as a par-
with high selectivity and affinity for the    varenicline should be initiated one week     tial nicotine agonist and selective nico-
α4β2 neuronal nicotinic acetylcholine         before the set date.2 Varenicline should     tinic receptor modulator. As a partial
receptors and is described as a partial       be taken after a meal with a full glass of   agonist, it eliminates the reward sensa-
nicotine agonist and selective nicotinic      water. The recommended dose for              tions associated with smoking: smok-
receptor modulator. Varenicline works         varenicline is 1 mg twice daily following    ing satisfaction, psychological reward,
by blocking the ability of nicotine to        a one-week titration schedule: 0.5 mg        enjoyment of respiratory tract sensa-
activate α4β2 receptors. These receptors      daily for 3 days, then 0.5 mg twice daily    tions, and craving reduction upon
are responsible for the stimulation of the    for 3 days, and then 1 mg twice daily        smoking. Varenicline is especially
CNS mesolimbic dopamine system,               through treatment. Patients should be        advantageous over other smoking ces-
which is believed to be the neuronal          treated initially for 12 weeks. If smok-     sation products in its ability to sustain
mechanism behind the reinforcement            ing cessation is successful, an additional   abstinence long-term. Additional re-
and reward effects of smoking.2               12-week treatment period is recom-           search is needed to investigate the use
      According to the manufacturer           mended to encourage long-term absti-         of varenicline in combination with
(Monge T, Medical Information Special-        nence. If patients are not successful af-    other smoking cessation therapies.
ist, Pfizer, personal communication, May      ter the initial 12-week course, factors
19, 2006), the safety and efficacy of         contributing to the failure should be        By
varenicline has currently been deter-         identified and resolved before a subse-      Emily Starr, Pharm. D. Candidate
mined in five unpublished, randomized,        quent course of therapy is attempted.2
double-blind, placebo-controlled studies           The most commonly encountered           References:
involving a total of 3330 subjects who        adverse event with varenicline was mild      1. Foulds J, Burke M, Steinberg M,
smoked cigarettes and were motivated to       to moderate nausea, reported in 30% of          Williams JM, Ziedonis DM. Ad-
quit. Three of the studies included a         patients treated with the 1 mg twice daily      vances in pharmacotherapy for to-
comparative arm versus bupropion SR.          dose. Other reported adverse events             bacco dependence. Expert Opin
With regard to bupropion SR, the first        with the 1 mg twice daily dose included         Emerg Drugs 2004;9(1):39-53.
two comparative 12-week studies found         insomnia (18%), headache (15%), gas-         2. Chantix® [package insert]. New
that subjects receiving varenicline dem-      trointestinal symptoms (8%), abnormal           York (NY): Pfizer Labs; 2006 May.

Page 2                                                                                                                     DIS News
Literature Highlight:
Fluoxetine Use in Patients With Anorexia Nervosa After Weight
Anorexia nervosa is a serious psychiatric     ine and placebo were titrated up from 20      Summary: Compared to placebo,
illness with a high rate of relapse follow-   mg/day to 60 mg/day over one week. In         fluoxetine does not demonstrate a signifi-
ing initial treatment. Depression, obses-     the event of an adverse reaction, the dose    cant benefit in the time to illness relapse
sive-compulsive disorder, or other psy-       was decreased at the discretion of the        in women recovering from anorexia ner-
chiatric illnesses may occur in persons       psychiatrist, and if there was a clinical     vosa.
with anorexia nervosa. Antidepressants        decline, an increase to 80 mg/day could
are commonly used to treat psychiatric        be initiated. In addition to drug therapy,
illnesses despite the lack of effectiveness   patients received cognitive behavioral        Walsh BT, Kaplan AS, Attia E, et al.
primarily due to the patient’s weight.        therapy during the 12-month study.            Fluoxetine after weight restoration in
Therefore, the use of antidepressant ther-                                                  anorexia nervosa. JAMA
apy for the prevention of relapse in pa-      Baseline characteristics were similar at      2006;295:2605-2612.
tients with anorexia nervosa who have         the time of randomization; however,
undergone weight restoration treatment is     patients receiving placebo had a small
of interest. A multicenter, randomized,       but significantly higher BMI than the         By
double-blind, placebo-controlled trial        treatment group. The primary endpoint         Reanna Brown, Pharm. D. Candidate
was conducted to evaluate the efficacy of     of the study was time-to-relapse. Forty
fluoxetine in reducing the rate of relapse    women completed the trial. Meeting
and enhancing psychological and behav-        defined criteria for relapse, experiencing
ioral recovery following initial treatment    treatment dissatisfaction, failing to at-
for anorexia nervosa.                         tend a minimum number of cognitive
                                              behavioral therapy sessions, or not ad-
Women 16 to 45 years old diagnosed            hering to the medication regimen were
with anorexia nervosa who had success-        reasons for discontinuation. Of those
fully completed treatment at one of the       patients that completed the 12-month
study sites to achieve and maintain a         trial, no significant difference in psycho-
minimum body mass index (BMI) of 19           logical state or BMI was found between
kg/m2 for two weeks were included.            fluoxetine or placebo. Multiple analyses
Those with serious other medical illness,     were conducted using different defini-
at risk for suicide, or on other medica-      tions of relapse; however, there was no
tions were excluded. Ninety-three             difference in the time-to-relapse found
women with a mean age of 23 years at          between the two groups.
two clinical settings were randomly as-
signed to receive fluoxetine (n=49) or
placebo (n=44) for 12 months. Fluoxet-

 Volume 10, Issue 7                                                                                                          Page 3
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   Phone: 406-243-5254
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