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The Clinician
The Outcome Resources Drug Information Newsletter
Volume 2, Issue 3
Answers to frequently asked drug questions...
Jim Joyner, PharmD, CGP
My patient has a sulfa allergy; which drugs
should they avoid ? The word “sulfa” refers
to sulfonamides which are a specific class of
antibacterial drugs. Common sulfa antibacterial drugs include Bactrim and Septra. There
are also a limited number of other drugs
which contain a sulfonamide-like configuration within their molecular structure. The anti
-inflammatory drug, Celebrex, is one of
these. Patients with sulfa allergies should
avoid all sulfonamide antibacterial drugs and
certain other drugs which contain a sulfonamide-like configuration.
Do not confuse the term “sulfa” with the
element sulfur, or sulfates and sulfites.
Sulfur, sulfites, and sulfates are not closely
related to sulfonamides an are not likely to
cause any adverse effects in people with a
“sulfa allergy”. Many commonly used
drugs are compounds which contain a sulfate
or sulfite component. Sulfates and sulfites are
just counter-ions that consist of sulfur and
oxygen which are used to chemically balance
many cationic drugs. Morphine sulfate is one
of these drugs. Drugs like morphine sulfate
do not pose any increased risk of adverse reaction to a patient with a “sulfa” allergy.
The presence of a sulfate or sulfite in the
name of a drug does not pose an increased
risk for drug allergy in a patient with a sulfa
allergy.
In addition to the sulfonamide antibacterial
drugs, patients with sulfa allergy may need to
avoid specific drugs from other pharmacologic classes that contain a sulfonamidelike configuration within their structure.
These include a select few drugs from the
following categories: diuretics, oral hypoglycemics, NSAIDs, and antiepileptic drugs.
The following table lists these specific drugs
as well as the sulfonamide antibacterial drugs.
Drugs to Avoid in Sulfa Allergic Patients
In this issue:
Sulfonamide antibacterials:
Sulfamethoxazole/TMP (Bactrim, Septra)
Sulfisoxazole (Gantrisin, Pediazole)
Sulfacetamide (Sulamyd Ophthalmic)
Sulfadiazine (Silvadene Cream)
Frequently
asked drug
questions
1
New drug:
Relistor
4
Thiazide diuretics:
Hydrochlorothiazide (Dyazide, HCTZ)
Metolazone (Zaroxolyn)
Oral hypoglycemics:
Glyburide (Diabeta, Micronase)
Glipizide (Glucotrol)
Comprehensive 4
Drug Review
Required in new
COP’s
Antiepileptic drugs:
Zonisamide (Zonegran)
Non-steroidal Anti-inflammatory drug:
Celecoxib (Celebrex)
Can opioids be administered by nebulizer for shortness of breath ? Opioids
are the mainstay of treatment for management of severe dyspnea in late stage CHF
and COPD. The use of opioids in dyspnea
is supported by extensive experience as
well as clinical studies with the use of both
oral and parenteral opioids, specifically
morphine. The mechanism of action is
unclear and it is interesting that opioids can
alleviate dyspnea in many patients without
changing the respiratory rate or producing
any measurable changes in blood gas parameters. The rationale for considering
nebulized opioids centers on the belief that
dyspnea can be relieved while avoiding
October 2008
Volume 3
Issue 4
potential systemic side effects associated with oral or parenteral routes. The current medical literature does not
support this belief. A review article by Foral (1) and
colleagues in 2004 evaluated a number of clinical studies in
patients being treated for dyspnea with inhaled nebulized
opioids. The authors concluded that the evidence did not
support the use of nebulized morphine for the relief of
dyspnea. They also reported that in all cases opioid side
effects were present from mild to moderate degree. There
are several other options available for conventional opioid
administration routes including, oral, subcutaneous, intramuscular, intravenous, rectal, transmucosal, and sublingual.
(1)
Nebulized Opioids use in COPD. Chest 2004;125:363-365
In light of the potential for only modest benefits balanced
against the potential for medication side effects and the fact
that slowing the dementia-related decline may not be a desired
goal in many hospice patients; the use of these drugs may not
be appropriate for the majority of hospice patients.
(1) Current Pharmacologic Treatment of Dementia: A Clinical Practice Guide-
line from the American College of Physicians and the American Academy of
Family Physicians. Annals of Internal Medicine 2008; 148,5: 370-378
Estimated Cost of Dementia Drugs:
Aricept 10mg daily
Exelon 6mg BID
Are dementia treatment drugs such as Aricept appropriate for continuation in a hospice patient ? There are currently 4 drugs used for management of dementia in the US.
They are Aricept (donepezil), Exelon (ravagstimine),
Razadyne (galantamine), and Namenda (memantine). The
American College of Physicians and the American Academy
of Family Physicians recently developed a clinical practice
guideline (1) which helps to address this question. The
AAFP– ACP guideline panel reviewed the clinical trials in
the medical literature and found only “limited evidence regarding the effectiveness of these drugs” for these outcomes:
cognition, global function, behavior/mood, and quality of
life/activities of daily living. The panel found evidence of
statistically significant improvements on certain observational grading scales (MMSE, ADAS-Cog), however, those
“improvements” were often not clinically significant. “The
magnitude of improvement in clinical trials often was so
small that patients or their caregivers may not be interested in exposing the patient to the potential side effects
of the drug for such a modest benefit,” says panelist Kenneth Schellhase, MD, MPH.
Potential Side Effects: Dementia Drugs
•
Nausea
•
Weight loss
•
Vomiting
•
Anorexia
•
Diarrhea
•
Bradycardia
•
Exacerbation of asthma and COPD
Most studies reported on the statistical significance of
changes in scale scores, however, patients, caregivers, and
clinicians are concerned with clinically important improvement. The panel concluded that there is insufficient evidence to determine the optimal duration of therapy. A beneficial effect, if any, would generally be observed within
3months of the start of therapy based upon information in
the trials. This effect could be an improvement or stabilization. In advanced dementia, stabilization or slowing the
decline may not be a desired goal if the quality of life is
judged to be poor.
Page 2
$95.00
$108.00
Namenda 10mg BID
$87.00
Galantamine 12mg BID
$75.00
(generic Razadyne)
*15 day supply
What works for hiccups ? A hiccup is an involuntary reflex
involving the respiratory muscles of the chest and diaphragm,
mediated by the phrenic and vagus nerves and a central
(brainstem) reflex center. A single episode can last for a few
seconds to as long as several days. Persistent hiccups can last
for months. There are a wide range of possible causes for hiccups including; stress or excitement, esophageal or gastric distension, liver disease, CNS lesions, or cancer. Irritation of the
vagus nerve or the diaphragm is a common mechanism.
Many drug and non-drug treatments have been used, but
there is little evidence of any one superior approach to management; virtually all current data are anecdotal. When choosing a drug treatment strategy, consider the patient’s drug
allergy history, potential drug-disease state contraindications, current level of function, and potential adverse effects from any proposed drug therapy.
Chlorpromazine (Thorazine) is the only drug with an FDA
approved indication for treatment of hiccups. Haloperidol
(Haldol) is a useful alternative. Chlorpromazine and Haloperidol should not be used in patients with Parkinson’s disease
because they may exacerbate involuntary movements. Metoclopramide (Reglan) increases GI motility and may be especially useful if hiccups are related to esophageal or gastric distention. The muscle relaxant, Baclofen (Lioresal), is thought
to have a direct relaxation effect upon the diaphragm and may
be most useful in patients where an irritation of the diaphragm
is suspected. Dexamethasone (Decadron) may be appropriate
as an adjunct to one of the previously mentioned drugs if there
is hepatomegaly or tumor involvement. All of these drugs are
available as low cost generics, so the choice of therapy should
The Clinician
be based upon the suspected etiology behind the hiccups, the
patient’s drug allergy history, and other health conditions that
may predispose the patient to adverse drug effects.
Drugs for Hiccups (singultus)
Chlorpromazine (Thorazine) 25-50mg Q6h po,pr
Haloperidol (Haldol) 1– 2mg Q6h po
Metoclopramide (Reglan) 10-15mg Q6h po
Baclofen (Lioresal) 5 –10mg Q6h po
Dexamethasone (Decadron) 2-6mg daily po
Is Megace a good drug for appetite stimulation in a hospice patient ? Megace (megestrol acetate) is a progestin-type
hormonal drug that has been used for appetite stimulation. It
has an FDA approved indication for the treatment of anorexia, cachexia, and unexplained weight loss in patients with
AIDS. Despite the very narrow indication, it has been
widely used for the treatment of weight loss in cancer patients, frail nursing home residents, dementia patients, and
frail elderly patients in the community with non-cancerous
chronic health conditions.
Studies in patients with cancer and AIDS have shown
Megace to be an effective appetite stimulant that is associated
with weight gain. Alternatively, studies in geriatric patients
including mostly nursing home residents have failed to demonstrate similar consistent benefits. Reports on the clinical
significance of Megace induced weight gain vary considerably. Some clinicians believe that the weight gains that have
been achieved with Megace are not related to reversing the
catabolic state of advanced disease, but reflect only increased
body fat or water retention.
The high cost of this drug coupled with the high volume of
use in non-approved applications stimulated numerous clinical
reviews and research reports regarding its effectiveness for treatment of weight loss and its adverse effects potential during the
past few years. The majority of these studies have been conducted in geriatric patients. To date, the reports in the medical
literature indicate only modest benefits at best and a potential for
serious adverse events. (1) A recent retrospective study by
Bodenner, et al. in The American Journal of Geriatric Pharmacology (June 2007), concluded that megestrol acetate was
associated with an increase in death among elderly nursing
home residents being treated for weight loss. A statistical
analysis by the authors demonstrated that the survival time of
those patients receiving Megace was on average 7.3 months less
than case matched cohorts who did not receive Megace and this
was determined to be highly significant. Furthermore their results found no significant increase in weight for their study population of 709 nursing home residents.
Volume 2, Issue 3
Deep venous thrombosis (DVT) is another potentially devastating adverse effect that has been associated with the use of
Megace for treatment of weight loss in elderly patients. A
2003 article by Kropsky, et al, reported a 5% incidence of
DVT in elderly nursing home residents receiving Megace for
treatment of weight loss.(2) DVT has been identified as a
significant risk of Megace therapy in geriatric patients by
other researchers as early as 2000 in the Journal of the
American Medical Directors Association and again in a 2003
review of cases by Marshall, et al (3,4).
There is sufficient evidence to formulate some guidelines
about which patients are at high-risk for potentially serious
adverse effects. Megace probably should not be used in the
following types of patients due to serious risks outweighing
potential benefits:
•
History of thromboembolic disease
•
Bed-bound, or otherwise immobile
•
Heart failure
•
Elderly patients
Estimated Cost of Megace for 15 days
Megace ES 625mg/5ml; 5ml once daily
$300.00
Megace has been shown to increase the appetite and induce
weight gain in non-geriatric adult patients with cancer or
AIDS, however, the weight gain may be due to increased fat
production or water retention, not lean muscle mass. Given
the current information, Megace would appear to have a very
limited role as an appetite stimulant in hospice patients.
Alternative drugs for appetite stimulation and treatment of
weight loss have included various agents from different pharmacologic classes: the steroid dexamethasone (Decadron);
the antidepressant mirtazapine (Remeron); and the antihistamine cyproheptadine (Periactin). All of these drugs have
potential side effects of varying significance, however, none
have been associated with an increased risk of death in the
elderly or increased risk of DVT. In addition these alternatives are all available as low-cost generics.
1. Bodenner, et al. The American Journal of Geriatric Pharmacology
2007;5(2):137-146
2. Kropsky, eta al. Journal of the American Medical Directors Association
2003;4:255-256
3. Bolen, et al Jouranal of the American Medical Directors Association
2000;48:248-52
4. Marshall, LL The Consultant Pharmacist 2003;18:764-63
Page 3
President & CEO: Martin McDonough, PharmD, CGP, DAAPM
Director of Operations: Ann McLaughlin
Director of Clinical Operations, Editor: Jim Joyner, PharmD, CGP
National Director of Business Development: Autumn Spence
Director of Client Services: Mary Davies
2217 Plaza Dr. Suite 200
Rocklin, Ca. 95765
Phone: 866-877-2053
Fax:
888-500-9023
Estimated Cost Comparison:
Xopenex vs Albuterol
Cost:
Nebulizer solution:
Is there a less expensive alternative for
the respiratory drug, Xopenex ?
Xopenex (levalbuterol) is a beta-agonist
type bronchodilator. Xopenex is very
similar to, and is in fact an isomer of the
earlier beta-agonist bronchodilator
albuterol. Albuterol and Xopenex are
both beta-2 selective agonist bronchodilators indicated for asthma and COPD.
Xopenex is more potent than Albuterol
on a milligram per milligram basis, so
theoretically Xopenex may have an advantage by having less risk of side effects
since less drug is required for therapeutic
effects. This theoretical advantage is not
proven out by the clinical studies which
have demonstrated comparable efficacy
and safety between Albuterol and Xopenex in both short-term and long-term
studies.
The safety and efficacy of levalbuterol
inhalation solution was evaluated in a 4week, multi-center, randomized, doubleblind, placebo-controlled study in 362
adult and adolescent patients 12 years of
age and older, with mild-to-moderate
asthma. Efficacy was measured by the
mean percent change from baseline in
FEV1. A dose of 0.63 mg of levalbuterol
and 2.5 mg of albuterol sulfate produced
a clinically comparable mean percent
change from baseline in FEV1 on both
day 1 and day 29. (1). No significant
difference in side effects was demonstrated as measured by heart rate, blood
pressure, and tremor. (1)
Albuterol is a more cost-effective
alternative to Xopenex which appears
to have very similar efficacy and a
similar safety profile. Xopenex should
be reserved only for those patients which
exhibit intolerable adverse effects to
albuterol, specifically: increased heart
rate, elevated blood pressure, and/or
tremor.
(1) Xopenex [package insert]. Marlborough, MA:
Sepracor Inc.; 2003.
(100 doses )
Xopenex
$370.00
Albuterol
$95.00
Metered-dose inhaler
Cost:
100 doses (2 inhalations)
Xopenex HFA
$54.00
Albuterol HFA
$36.00
Comprehensive Drug Review is Part of
the New Federal Hospice Conditions for
Participation: Extensive new federal Hospice Conditions for Participation (COP’s)
were published in the Federal Register June
5, 2008. These regulations will become effective on December 2, 2008. A documented
comprehensive assessment of each patient is
required which must identify patient needs
across the entire spectrum of hospice related
care. Part of this assessment entails a review
of each patient’s drugs both prescription and
OTC drugs, including herbal remedies. The
review should address at least the following:
1) Effectiveness of drug therapy
2) Drug side effects
3) Actual or potential drug interactions
4) Duplicate drug therapy
5) Drug therapy currently associated with
lab monitoring
With regard to the drug regimen review, the
hospice is required to ensure that the interdisciplinary group confers with an individual
with education and training in drug therapy
management . This individual may be an
employee of the hospice or under contract
with the hospice to ensure that drugs and
biologicals meet the patient’s individual
needs. In most cases this individual would
be a clinical pharmacist.
Relistor: New Drug for of Opioid
Induced Constipation.
Clinicians now have a unique new
medication for management of
opioid induced constipation. Relistor (methylnaltrexone) is an opioid
antagonist which acts peripherally
to block the effects of opioid drugs
on the GI tract resulting in a decrease in the constipating effects of
opioids. Due to the fact that
methylnaltrexone is a quaternary
amine, it is not absorbed across the
blood-brain barrier and does not
have any impact on the opioid mediated analgesic effects.
Results of a double-blind, placebo controlled clinical study of
154 patients showed that 60% of
the Relistor treated patients had
laxation within 4 hours of a single
dose compared with only 14% of
patients that received a placebo.
In clinical trials, 30% of patients
who received Relistor reported
laxation in as little at 30 minutes.
Possible side effects include: nausea, vomiting, diarrhea, abdominal
pain, and dizziness.
The usual dosage is 8 to 12mg
by subcutaneous injection every
other day as needed. The drug is
not available for oral use. Currently it is only available in a
12mg/0.6ml single use vial. If a
dose of less than 12 mg is used, the
remaining drug left in the vial is
supposed to be discarded. The approximate cost to the hospice for a
2 week supply is $320.00 assuming
that the drug is administered at a
dose of 12mg on every other day.
Relistor is not a first-line drug for
treatment of constipation in hospice
patients, however, it may be appropriate for the patient with severe
opioid induced constipation who
has not responded to traditional
laxative therapy and who also has
constipation that failed to improve
with rotation to different opioids.