PostScript A Newsletter from UniCare, Inc.

March 2005

UniCare Medical Record Department

Many of you already know that we have the ability to provide your facility with physician orders, MARs, treatment records, behavior documentation records,

pain management records and ADL records. Because we have a proprietary system, we can design these records to meet the needs of your facility. We pride ourselves on having a group of employees processing these records who are seasoned and knowledgeable.

If we are not currently processing your medical records and you would like for us to start, please contact Debbie Barnes.

If we are already processing your records, we want to remind you that we can process lists for you from your physician orders. Your facility can have six lists per month at

no charge. Additional lists can be obtained for a minimal cost.

If you have any questions regarding this service, please call Debbie Barnes at

1-800-243-6126 or (334) 365-6502. If you want to add, delete or change your lists, you can call our switchboard and give Dale or Lynda your facility name. They will put you through to your medical records representative.

Namenda – How to get approval by Alabama Medicaid

The prior approval office only requires that a patient score a 14 or less on a MMSE test and fill out the appropriate paperwork. That’s all. Namenda can be used:

for moderate to severe Alzheimer’s disease;

in combination with an ACHEI or as monotherapy; and

it has low potential for drug-drug interactions.

Please call your UniCare consultant pharmacist if you would like to schedule an in-service on Namenda or if you have any questions.

TITLE PAGE

Overactive Bladder

NEW DRUGS/FORMULARY INFO

Darifenacin (Enablex) and Solifenacin (Vesicare)

Darifenacin and solifenacin are M3 selective antimuscarinic medications that primarily affect the detrusor muscle in the bladder. They were recently FDA-approved for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Darifenacin (Enablex) was evaluated in three randomized, fixed-dose, placebo-controlled, multicenter double-blind 12-week trials that included adults up to age 93 years. Darifenacin decreased incontinence episodes per week, micturitions per day and volume of urine per void. In the elderly, darifenacin therapy should be started at a dose of 7.5 mg/day. For persons with moderate hepatic impairment or when co-administered with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin and nefazodone) the daily dose should not exceed 7.5 mg. The dose of darifenacin does not have to altered in persons with renal impairment.

The efficacy of solifenacin was evaluated in four 12-week, double-blind randomized placebo-controlled trials that included patients older than 65 years of age. The studies measured reductions in the number of micturitions/day, number of incontinence episodes/day and mean volume voided per micturition with solifenacin. The starting dose is 5 mg/day, which can be increased to 10 mg/day. For most elderly patients 5 mg should be the maximum daily dose as many elderly persons have creatinine clearance < 30 ml/min and/or moderate hepatic impairment. Solifenacin is metabolized by CYP3A4 and therefore should be used cautiously and at the 5 mg dose in patients receiving CYP3A4 inhibitors.

Both drugs should be swallowed whole and may be taken with or without food and are contraindicated in persons with urinary retention, gastric retention and uncontrolled narrow-angle glaucoma. Remember to check your state and local preferred drug lists before prescribing.

Geriatric Pharmaceutical Care Guidelines® 2005 Edition

Your Omnicare Pharmacy will be providing you with copy of the 2005 edition of the GPCG released this month. Once again, the GPCG was reviewed by over 100 external experts from practice and academic settings around the country, and a 12-member Pharmacy and Therapeutics Committee, chaired by Dr. Eric Tangalos, Professor of Medicine and Chair, Division of Community Internal Medicine, Mayo Clinic Rochester, MN. The drug monographs were prepared by the Geriatric Pharmacy Institute of the Philadelphia College of Pharmacy, at the University of the Sciences in Philadelphia before being reviewed and then endorsed by the American Geriatrics Society. There are several key features and improvements in the publication since last year.

q Nearly 700 pages of geriatric focused pharmaceutical information, rating drug therapies for clinical effectiveness and relative costs

q evidence tables, chapter text, algorithms, critical pathways, MDS-Med Guides and appendix

q Now 53 Chapters of Clinically Reviewed Drugs … including, in this edition, a long-awaited new feature…

q 35 of these chapters now include invaluable Dosage Adjustment Requirements tables … addressing age, renal impairment (both mild to moderate and moderate to severe) and hepatic impairment patient variables

q Has moved from an indication-specific format to an outcomes-based resource

q With cross-class comparisons and practice guidelines

q Health Management Algorithms … Now 23 in number … invaluable tools for geriatric practitioners

q Valuing Quality: Avoiding Overuse, Misuse and Underuse of Medications

q Completely Updated Opening Chapter … Addressing many of the concerns that have been raised with regard to the quality of drug therapy in older adults … an important, significantly referenced commentary.

q One Very Significant New Chapter … replacing and expanding upon the ANEMIA chapter of the prior edition - CHRONIC KIDNEY DISEASE

q Agents for Anemia, Hyperphosphatemia, Metabolic Acidosis, Renal Osteodystrophy, Restless Legs Syndrome, Uremic Bleeding, Uremic Pruritis and Vitamin Supplementation

q Three Vastly Expanded Chapters … a tribute to their significance in contemporary senior healthcare

q HYPERLIPIDEMIA – now includes National Kidney Foundation Guidelines, as well as the prior ATP III Guidelines

q PERIPHERAL ARTERIAL DISEASE – now includes a review of the lipid-lowering agents and antihypertensive agents for event reduction

q STROKE PREVENTION – now emphasizes the use of agents for stroke prevention in specific high-risk patients, along with an updated algorithm for stroke prevention

q New Reference Section … sure to be a frequently used GCPG feature by nursing personnel

q Drug Administration Recommendations Regarding Meals … an important, reliable, annually updated resource

DRUG INDICATIONS /WARNINGS

Name Confusion between Zyprexa and Zyrtec

There are 79 reports of antipsychotic drug olanzapine (Zyprexa) being incorrectly dispensed for the antihistamine cetirizine (Zyrtec) and vice versa. In addition to having similar brand names, both drugs are taken once daily and are available in similar doses. Eli Lilly, manufacturer of Zyprexa, said it plans to change the label for the 10 mg bottles of Zyprexa for easier identification.

Eli Lilly posted a health professional’s letter on the FDA web site indicating that these errors have led to adverse events in some instances and such mix-ups may lead to "potential relapse in patients suffering from schizophrenia or bipolar disorder." In the letter, Lilly also included recommendations from the Institute of Safe Medication Practices, which suggested that pharmacies should store the drugs in different locations and that prescribers should print both the brand and generic names for the drugs on prescriptions.

This information reminds us all to read labels carefully and double-check both the brand and generic drug name before dispensing or administering medications. The Eli Lilly letter is available at http://www.fda.gov/medwatch/SAFETY/2005/zyprexa.htm.

PATIENT CARE

Overactive Bladder

Many aging Americans suffer from symptoms of overactive bladder that curtail their participation in social activities and can lead to isolation, sleep disruption, and urinary incontinence. Typically people with overactive bladder complain of urinary urgency, urinary frequency (voiding > 8 times in a 24 hour period) and nocturia (awakening two or more times at night to void). The prevalence increases with age and affects 42% of men and 31% of women aged 75 or older.

The symptoms of overactive bladder are usually associated with involuntary contraction of the detrusor muscle. There are many conditions that contribute to symptoms of overactive bladder including lower urinary tract infection, obstruction, and impaired bladder contractility. In women estrogen deficiency and urinary sphincter weakness can precipitate urgency. In older men benign or malignant prostatic enlargement can contribute to detrusor overactivity. In addition, there are a number of neurological disorders including stroke, Alzheimer disease, multi-infarct dementia, Parkinson’s disease, multiple sclerosis, and diabetic neuropathy that cause or worsen symptoms of overactive bladder. Many chemicals (e.g. diuretics, caffeine, alcohol, theophylline) increase urinary urgency and frequency making overactive bladder worse and confusing the diagnosis. Constipation should be avoided in persons with overactive bladder to avoid straining upon defecation.

Many non-pharmacologic/behavioral interventions that have been found to improve symptoms of overactive bladder (such as pelvic exercises) are difficult to implement in the frail elderly. However, we can assure that residents have good bladder and bowel habits and avoid precipitants such as caffeine and alcohol. Table 1 lists medications that may contribute to symptoms of overactive bladder.

Table 1: Medications That May Contribute to Symptoms of Overactive Bladder

Class of Medication	Examples	Mechanism	Recommendations
Diuretics	Furosemide (Lasix) Bumetanide (Bumex) Torsemide (Demadex)	Cause a rapid increase in bladder volume which precipitates urgency	Consider changing the time of dose or consider different diuretic (thiazide) if feasible
Narcotic Analgesics	Codeine Morphine (MS Contin, Avinza) Fentanyl (Duragesic) Tramadol (Ultram)	Decrease bladder contractility and may cause urinary retention	Discontinue as soon as possible
Tricyclic antidepressants	Amitriptyline (Elavil) Nortriptyline (Pamelor) Desipramine (Norpramin)	May cause urinary retention and decrease bladder contractility	Consider changing to other antidepressants such as escitalopram (Lexapro) or sertraline (Zoloft)
Sedating antihistamines	Diphendydramine (Benadryl) Hydroxyzine (Atarax)	Cause sedation. May cause urinary retention and decrease bladder contractility	Discontinue as soon as possible Consider use of non-sedating antihistamines if needed for pruritis or allergic rhinitis
Benzodiazepines	Diazepam (Valium) Chlordiazepoxide (Librium) Lorazepam (Ativan) Alprazolam (Xanax) Flurazepam (Dalmane) Oxazepam (Serax)	Cause sedation. May cause urinary retention and decrease bladder contractility	Discontinue as soon as possible Consider non-pharmacologic intervention for insomnia

Drug Therapy Treatment of Overactive Bladder

Many classes of medication have been studied for the treatment of symptoms of overactive bladder. However, pitfalls limit the quality of existing studies in this area. Table 2 lists drugs with proven clinical evidence. Other agents (hyoscyamine, propantheline, vaginal estrogen preparations, and imipramine (Tofranil) lack scientific support and are not recommended for treatment of overactive bladder in the elderly. Alpha-adrenergic blockers such as alfuzosin (Uroxatral) and tamsulosin (Flomax) are indicated for benign prostatic hyperplasia and may help symptoms such as frequency and urinary retention in men with overactive bladder.

Table 2: Recommended Drugs with Proven Efficacy in the Treatment of Overactive Bladder

Antimuscarinic Medication	Usual Adult Dose	Comments
Oxybutynin long-acting (Ditropan XL)	5 – 30 mg daily orally 3.9 mg over a 96-hr period (transdermal)	Avoid short-acting oxybutynin due to side effects. Transdermal patch can cause irritation
Tolterodine long-acting (Detrol LA, Oxytrol)	4 mg daily orally	Avoid short-acting tolterodine due to side effects
Trospium (Sanctura)	20 mg twice daily orally	Purported to have fewer CNS effects than other antimuscarinics; but not shown in clinical studies
Solifenacin (Vesicare)	5 – 10 mg daily orally	Dosing reduction needed in renal and hepatic impairment. Potential for significant drug interactions.
Darifenacin (Enablex)	7.5 – 15 mg daily orally	Dosing reduction needed in hepatic impairment. Potential for significant drug interactions.

Well-conducted studies comparing long-acting forms oxybutynin (Ditropan XL) and tolterodine (Detrol LA) have shown that the drugs have similar efficacy and effectiveness alone and when combined with various types of behavioral intervention. Long-acting forms of oxybutynin and tolterodine are equal in efficacy and effectiveness to short-acting forms of the drugs but have the advantage of producing fewer CNS and cardiovascular side effects.

Trospium (Sanctura) has been compared to short-acting oxybutynin and found to have fewer side effects. However, trospium has not been compared to long-acting forms of antimuscarinic medications. Despite the fact that trospium is a quaternary ammonium compound and should NOT cross the blood-brain barrier, the drug exhibits some CNS side effects and may not offer an advantage over long-acting forms of oxybutynin or tolterodine.

Darifenacin (Enablex) and solifenacin (Vesicare) are antimuscarinic drugs with selective M3-receptor antagonist actions and theoretically fewer anticholinergic side effects than other antimuscarinic drugs. However, the theory has not been tested in clinical trials. No conclusions can be drawn about the relative safety of these newer agents compared to Detrol LA or Ditropan XL.

Clinical Effects of Antimuscarinic Medications

Clinically significant improvement in symptoms of overactive bladder is defined as a reduction in incontinence episodes by more than 50%. Many studies look at other endpoints as well, including reduction of urinary frequency (i.e. voids/day) and reduction of nocturia. However, unless incontinence episodes can be reduced, the clinical value of treatment is difficult to justify given the inherent adverse effect profile of antimuscarinic medications.

When used in therapeutic doses antimuscarinic medications have been shown to reduce nocturnal awakenings, incontinence episodes, micturition frequency, urge frequency and urge severity. Pharmacologic treatment improves symptoms but does not eradicate the problem.

Adverse Effects

All antimuscarinic medications have some degree of anticholinergic side effects. Although dry mouth is the most common, constipation, gastroesophageal reflux, blurryed vision, urinary retention, and cognitive side effects can also occur. Since various forms of dementia are routinely treated with cholinesterase inhibitors (Donepezil (Aricept), Rivastigmine (Exelon), or Galantamine (Reminyl)) in our population, the concern about adverse cognitive effects and delirium due to antimuscarinic drugs is significant. Data suggest that oxybutynin has more central nervous system effects than tolterodine or trospium. Many of the systemic anticholinergic side effects are reduced with the use of long-acting formulations of these medications. However, all elderly persons treated with antimuscarinic medications should be monitored for anticholinergic side effects, as well as drug interactions.

Central anticholinergic side effects are believed to be mediated by M1 muscarinic receptors. Tolterodine and oxybuytinin are non-selective antimuscarinic agents that antagonize M1, M2 (cardiovascular) and M3 (detrusor muscle) receptors. Darifenacin (Enablex) and solifenacin (Vesicare) are selective M3 muscarinic receptor antagonists that have been shown to cause central nervous system effects similar to placebo, however these newer drugs have not been compared to long acting oxybutynin and tolterodine in clinical trials. All older persons receiving medications with antimuscarinic (anticholinergic) properties should be evaluated on an ongoing basis for changes in cognitive function including confusion due to delirium.

Summary

It has been estimated that 33 million Americans experience the symptoms of overactive bladder. There are new treatments that look promising in the management of symptoms in elderly persons but head-to-head clinical trials are needed to conclude that they have superior efficacy or safety over existing therapy.

Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: Report from the standarisation sub-committee of the international continence society. Urology 2003:61;37-49.

Ouslander JG. Management of overactive bladder. N Engl J Med 2004;350:786-799.

Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry 2001;62(Suppl 21):11-14.