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HEALTHLINE
February 2005
NEW DRUGS/FORMULARY INFO
Pregabalin (Lyrica) for Neuropathic Pain
Pfizer Inc. received Food and Drug Administration approval for Lyrica (pregabalin capsules) for
the management of neuropathic pain associated with diabetic peripheral neuropathy and
postherpetic neuralgia (Shingles). Pregabalin is classified as a controlled substance. Pregabalin
was developed by Pfizer as a follow-up compound to gabapentin (Neurontin). It is a neurological
agent that is also under investigation for a variety of neurological and psychological disorders and
is believed to decrease pain by interfering with a subunit of calcium channels called alph-2delta
found on overexcited nerve cells.
The efficacy of pregabalin was established in six double-blind, placebo-controlled trials, three
involving patients with diabetic peripheral neuropathy and three involving patients with shingles.
Pregabalin provided rapid and clinically meaningful pain reduction in a significant portion of
patients, with pain relief beginning as early as the first week of treatment in some patients. Pain
relief was sustained in studies of up to 12-weeks duration at an average dose of 300 mg/day of
pregabalin. The most frequent adverse effects are somnolence, dizziness, peripheral edema,
headache and dry mouth. The product should become available in the next few months.
Sabatwoski R et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic
neuralgia: results of a randomized, placebo-controlled clinical trial. Pain 2004;109:26-35.
Rosenstock J, et al. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebocontrolled trial. Pain 2004;110:628-38.
DRUG INDICATIONS / WARNINGS
The Latest on COX-2 and NSAID Safety
Since the withdrawal of rofecoxib (Vioxx) from the U.S. market, three additional safety alerts have
been issued for cyclooxygenase selective (COX-2) and nonselective (NSAID) nonsteroidal antiinflammatory drugs – valdecoxib (Bextra), celecoxib (Celebrex) and naproxen (various otcs
Aleve™ and legend Anaprox, Naprosyn). The Food and Drug Administration (FDA) is evaluating
data submitted by the respective drug companies to determine the appropriate regulatory action.
Although these are important findings, at this point the FDA has seen only the preliminary results
of the studies.
In overall clinical studies the most common side effects are dyspepsia, diarrhea and abdominal
pain, which are generally mild to moderate. NSAIDs and COX-2 agents pose inherent safety
concerns in older persons due to the potential for gastrointestinal ulceration and bleeding, renal
failure, hypertension, and heart failure. NSAIDs and COX-2s should be used with caution in
patients with fluid retention, hypertension, or heart failure.
Recently, studies have noted new cardiovascular risk. In brief, the situations leading to potential
safety concerns include:
-
higher rate of serious cardiovascular thromboembolic events (e.g. heart attack, stroke
accident) in valdecoxib (Bextra) treated patients in two studies immediately following
coronary artery bypass graft surgery (CABG) (valdecoxib is not FDA-approved for post
surgical use following CABG);
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3.4 times greater risk of cardiovascular events (e.g. heart attack and stroke) compared to
placebo in a clinical trial of celecoxib (Celebrex®) to prevent colon polyps in patients
taking 800 mg/day; 2.5 times greater risk in patients taking celecoxib 400 mg/day.
Celecoxib in doses of less than or equal to 200 mg/day has not been associated with an
increased risk of heart-related complications, and;
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HEALTHLINE
February 2005
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50% or 0.5 times greater risk of cardiovascular events compared to placebo in a clinical
trial of naproxen being conducted to determine if naproxen or celecoxib would reduce the
risk of developing Alzheimer’s disease. Naproxen is a Beers drug and is not
recommended for use in the elderly because of its long half-life, associated edema and
gastrointestinal adverse effects.
Based on this information, it appears that celecoxib can be continued safely at doses of 200
mg/day or lower. Persons receiving celecoxib doses of greater than 200 mg/day should be
reevaluated for possible dosage reduction or selection of replacement therapy. As well, the risk to
benefit ratio of continued treatment with naproxen should be reevaluated in light of this new
information. As with all medications, the lowest possible dose of NSAIDs/COX-2s should be used
for the shortest possible period of time needed. Non-acetylated salicylates (Disalcid and Trilisate)
and acetaminophen are appropriate alternatives for the treatment of pain and inflammation in
older persons.
PATIENT CARE INFORMATION
Cranberries and UTI Prevention
Ingestion of cranberry juice has been shown to be effective in decreasing bacteriuria with pyuria,
but not bacteriuria alone or symptomatic urinary tract infection (UTI), in an elderly population.
When combined with lingonberry, cranberry juice was demonstrated to reduce the rate of
recurrent UTI in younger women. A randomized trial compared placebo, cranberry juice, and
cranberry tablets (1:30 parts concentrated juice) for the prevention of UTIs in sexually active
women aged 21 to 72 years. In this study, the women taking cranberry juice or tablets
experienced significantly fewer symptomatic UTI over a period of 1 year. 1 Thus, although the
efficacy of cranberry juice for the prevention of UTI needs further evaluation, there is mounting
evidence that it may be effective in young, otherwise healthy women. 2 There was a 50% of the
number of symptomatic UTIs per year and a 50% decrease in annual antibiotic consumption. A
limitation of the cranberry juice concentrate is the taste. Most trials have used cranberry juice
concentrate doses of 250 – 300 ml three times a day. If sweetened juice concentrate is used,
blood sugars need to be monitored carefully in diabetic patients due to the high caloric load
associated with adequately effective doses of cranberry.
1. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as
prophylaxis against urinary tract infection in women. Can J Urol 9:1558, 2002.
2. Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev
(1):CD0013213, 2004.]
Glaucoma
Loss of vision in the elderly can profoundly affect their quality of life, and, can result in an
increased incidence of falls, as well as a decline in activities of daily living. Long-term care
residents with vision impairments may require more nursing care, exhibit frustration-inducing
agitation and withdraw from activities.
There are several common causes of visual loss but this article focuses on glaucoma. This is an
area that depending on the transfer of medical information and the follow-up of eye care
specialists to your nursing facility, can be underdiagnosed, undertreated or treated with less than
optimal medication.
The Centers for Medicare and Medicaid also elevated the importance of identifying and treating
glaucoma through The Benefits Improvement and Protection Act of 2000 (BIPA). This act
provides coverage for annual glaucoma screening for eligible Medicare beneficiaries. These
beneficiaries are eligible for this benefit if they 1) have family history of glaucoma, 2) are diabetic,
3) or are African-American over the age of 50.
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February 2005
Glaucoma is a slow progressive optic neuropathy. It is caused by poor drainage of aqueous
humor from the eye, resulting in an increased intraocular pressure (IOP) outside the normal range
of 10-20 mm/Hg, degeneration of the optic nerve head and a restricted visual field. The
significance of consistent reduction of IOP was demonstrated in the Advanced Glaucoma
Intervention Study (AGIS-7) study funded by the National Eye Institute in 2000. This study also
concluded that IOPs should be consistently below 14 and that decreasing diurnal variations in
IOP slow the progression of visual field loss.
All drugs for treating glaucoma either reduce the rate of aqueous humor production or increase
the drainage from the eye. Agent selection is based on efficacy and compliance with safety
obviously being considered. Because eye drops are absorbed through the mucous membrane,
they may have considerable systemic effect and side effects can be profound. As an example,
Betoptic-S® has 2.5% ocular absorption. Therefore, both oral therapies and eye drops must be
considered in assuring against drug related problems. Ideally the best treatment is an effective
agent administered once a day, with comfortable drop size and feel and lack of side effects.
Available medications include:
Class
Miotics
Medications
Pilocarpine,
epinephrine and
in combination
Beta-Blockers
Carbonic
Anhydrase
Inhibitors
(CAI)
Alpha2
Agonists
CAI/timolol
combination
Prostaglandin
Analogues
Betoptic-S®
(Cardioselective)
Betagan®,
timolol
(Timoptic®)
Trusopt® and
Azopt®
Iopidine®
Brimonidine
Alphagan-P®
Cosopt®
Usual Dosing
Four times daily
Twice daily
Two or three
times daily
Two or three
times daily
Twice daily
Travatan®
Once daily
Xalatan®
Lumigan®
*Refer to the literature for complete product information
Side effects
Tearing, reduced
night vision,
headache
Stinging, burning,
blurred vision
Decreased heart
rate and BP
Bronchospasm
Insomnia
Burning, tearing
Dry mouth
Lethargy
GI upset
Conjunctival
hyperemia
Lethargy in elderly
Burning and tearing
Dry mouth
Lethargy
Decreased heart
rate and BP
Bronchospasm
Insomnia
Hyperemia
Iris color change
Eyelash changes
Contraindication
Acute iritis
History of retinal
detachment
Highly myopic eye
Coexisting cardiovascular
or respiratory disease
Allergy
Allergy
Allergy
Allergy
Coexisting cardiovascular
or respiratory disease
Allergy
Timolol, a non-selective beta blocker had been the most frequently prescribed first-line therapy
through the 1990’s. With concern for using timolol in residents with coexisting cardiovascular or
respiratory disease, the introduction of prostaglandin analogues (e.g. Travatan) has allowed
these agents to be used more frequently as first-line or adjunctive therapy.
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distributed by PBM Plus, Inc.
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HEALTHLINE
February 2005
Challenges in administration also include the residents’ tolerance, compliance with regulatory
issues and efficacy surrounding the use of multiple eye drops. Monotherapy is cost effective,
saves considerable administration time and improves medication adherence along with outcome.
As is the case with many disease, monotherapy is the most desirable treatment regimen however
optimal IOP lowering may require appropriate combination therapy.
Areas that should receive scrutiny include:
- Residents that carry a diagnosis of glaucoma and have no treatment
- Residents that are receiving pilocarpine or other therapies that require administration two,
three or four times a day
- Residents receiving oral and topical agents that increase the potential for drug related
problems
- Residents receiving beta-blockers that have cardiopulmonary contraindications such as
asthma or Sick Sinus Syndrome
- Residents receiving multiple eye drops that might be changed to monotherapy to reduce
administration time and assure efficacy through proper absorption
Proper administration techniques should be reviewed periodically with the nursing staff. The
bottles should be kept tightly closed and the expiration dates should be checked regularly. When
dosed appropriately, the individual bottle should only last through the expected administration
period. If more than one topical ophthalmic drug is administered, drops should be instilled 5-10
minutes apart to assure proper absorption.
Eye drop medications without proper documentation and follow-up can lead to an incomplete
medical history that may occur unless residents or their caregivers are queried about all
medications they are taking. As we are concerned about the implications of polypharmacy, we
must be aware of all forms of medications as well as those taken over-the-counter.
Falls and fractures are a devastating occurrence and blindness is a frightening prospect. Given
the level of attention to this disease, no person should become blind because of underdiagnosed,
untreated or suboptimally treated glaucoma. Glaucoma is another condition that is predisposed to
medication misuse, overuse and underuse.
The Omnicare Geriatric Pharmaceutical Care Guidelines 2004; 279-285
Novack, Gary. New Glaucoma Medications in the Geriatric Population: Efficacy and Safety. JAGS 2002 50:956-962
Lord, Stephen. Visual Risk Factors for Falls in Older People. JAGS 2001 49:508-515
Fiscella, Richard. Pharmacological Considerations in the Treatment of Glaucoma. Managed Care Supplement 16-20.
The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS-7) The relationship between control of
intraocular pressure and visual field deterioration. Am J Ophthal 2000;130:429-40.
Editorial Board
Karen Burton, R. Ph., GCP, FASCP
Mark Coggins, Pharm. D., GCP, FASCP
Kelly Hollenack, Pharm. D. CGP
Philip King, Pharm. D., GCP, FASCP
Susan Kleim, B.S., Pharm., GCP, FASCP
Terry O’Shea, Pharm. D., GCP, FASCP
Elmer Schmidt, Pharm. D., GCP, FASCP
Barbara J. Zarowitz, Pharm. D., GCP, FASCP
Copyright 2005
All Rights Reserved
Published by Omnicare, Inc.
distributed by PBM Plus, Inc.
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