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| .pct){width="0.99 | # **American Society of Consultant Pharmacists** |
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May 24, 2002

Dockets Management Branch

HFA-305

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

#### RE: Docket number 02N-0115

The American Society of Consultant Pharmacists is pleased to provide
input to the Food and Drug Administration on the important issue of risk
management for prescription drugs. The FDA is to be commended for
devoting attention to this issue and seeking ways to improve the current
structure and systems for managing risk associated with prescription
medications. Our comments will include a focus on risk management issues
as they relate to older adults and long-term care settings.

The American Society of Consultant Pharmacists (ASCP) is the
international professional association that provides leadership,
education, advocacy, and resources to advance the practice of senior
care pharmacy. Consultant pharmacists specializing in senior care
pharmacy practice are essential participants in the health care system,
recognized and valued for the practice of pharmaceutical care for the
senior population and people with chronic illness. In their role as
medication therapy experts, consultant pharmacists take responsibility
for their patients\' medication-related needs; ensure that their
patients\' medications are the most appropriate, the most effective, the
safest possible, and are used correctly; and identify, resolve, and
prevent medication-related problems that may interfere with the goals of
therapy. ASCP\'s 7,000 members manage and improve drug therapy and
improve the quality of life of geriatric patients and other individuals
residing in a variety of environments, including nursing facilities,
subacute care and assisted living facilities, psychiatric hospitals,
hospice programs, and in home and community-based care. Visit ASCP\'s
Web site at www.ascp.com.

To better achieve reduction of risk associated with prescription drug
use, ASCP supports increased funding for the Food and Drug
Administration, especially for the Office of Drug Safety and the
MedWatch Program. With more resources, the MedWatch Program could:

-   Increase marketing and awareness of the program among health
    professionals and consumers

-   Conduct more rapid data analysis and aggregation to quickly identify
    trends and patterns with regard to medication adverse effects

-   Provide timely feedback to health professionals, both to individuals
    who submit reports to MedWatch and aggregate reporting of adverse
    drug event trends and patterns in a manner. These aggregate reports
    could be in the form of a web site or periodic e-mail summaries.

Older adults are especially vulnerable to the risks of medication use.
They take more medications than other persons and are more likely to
have diminished ability to metabolize drugs due to declining kidney and
liver function. Adverse drug reactions are observed two to three times
more frequently in geriatric patients than in adult patients younger
than 30 years. It is also estimated that adverse drug effects are
responsible for up to 10% of hospital admissions in older patients.^1^

Older adults consumer 30-40% of all prescription drugs, yet few older
adults are typically included in clinical trials prior to marketing.
Once a medication is approved for marketing, manufacturers have less
incentive to conduct or sponsor trials in older adults. Research on drug
use is particularly lacking for use of medications in the frail elderly,
those age 85 and over, who often reside in long-term care settings.
Information on prescription drug risks in this population is difficult
to obtain. ASCP supports increased research on drug use in older adults
and the development of strategies to encourage funding of such research
by pharmaceutical manufacturers or federal agencies.

# Risk communication

In the past 30 years, the number of medications available for use by
physicians and other prescribers has grown substantially. In earlier
years, physicians could learn a few key medications in each therapeutic
category and gain experience and knowledge with those medications.
Today, the average prescriber confronts dozens of drug formularies from
the various health plans used by their patients. As a result,
prescribers today must be able to use virtually all of the available
drugs to treat the types of conditions or patients being managed.

At the same time, the amount of information available today is
exploding. Prescribers receive information by mail, FAX, e-mail, web
sites, personal contact, and other methods. Information comes from
medical journals, pharmaceutical companies, government agencies, and
many other sources.

One question on which FDA has requested input is: How can communication
with health care professionals be more effective? How can the FDA cut
through the information overload and background noise to ensure that
health professionals are not only aware of, but also apply important
information about risks of medications in their patient interactions?

## ASCP Suggestion on Risk Communication

In response to this question, we offer an idea for consideration. The
idea is based on a strategy that FDA currently uses when issuing notices
about recall of medications. A Class I recall is a situation in which
there is a reasonable probability that the use of or exposure to a
violative product will cause serious adverse health consequences or
death. A Class II recall is a situation in which use of or exposure to a
violative product may cause temporary or medically reversible adverse
health consequences or where the probability of serious adverse health
consequences is remote. A Class III recall is a situation in which use
of or exposure to a violative product is not likely to cause adverse
health consequences.

This system of prioritizing medication recalls enables health care
professionals to quickly identify situations where urgent action is
needed to avoid loss of life. The class of the recall provides guidance
to the practitioner on the urgency and importance of the issue.

Perhaps the FDA should consider developing a similar prioritized system
for issuing "Medication Safety Alerts". A Class I Medication Safety
Alert would involve a situation where patient lives may be lost or
serious adverse health consequences may occur if certain precautions or
actions are not taken with use of the designated medication. The
information about the need for liver monitoring with the use of
troglitazone, for example, might have fit into a Class I Medication
Safety Alert category. The drug recall framework might also be used to
establish guidelines for Class II and Class III Medication Safety
Alerts.

These Medication Safety Alerts should be provided in a consistent format
and should emphasize information in four key areas:

-   DESCRIPTION of the safety issue or problem

-   Strategies to PREVENT the adverse effect (e.g. avoid use of drug in
    patients with heart failure, or conduct a baseline EKG to rule out
    abnormalities prior to initiation of therapy)

-   Strategies to promptly DETECT or identify the problem (e.g. monthly
    liver panels, or education of the patient about early signs or
    symptoms of the problem)

-   Strategies for RESPONDING to the adverse event when it occurs

# Existing tools for risk management

In recent years, a number of medications have been identified which
present significant risk of harm if not used appropriately. The
safeguards inherent with the use of prescription medications in the
United States have been found to be inadequate for safe use of these
particular medications. In some cases, medications have been withdrawn
from the market. In other cases, special risk management programs have
been established in an effort to better manage the risks from the
medication.

### Withdrawal from the market

When useful medications are withdrawn from the market, patients who
could benefit from them are deprived of the benefits. The withdrawal of
cisapride heightened ASCP's interest in the medication risk management
issue. Cisapride was a medication used to increase motility of the upper
gastrointestinal tract, and of value in managing a common complication
of diabetes called diabetic gastroparesis. Without cisapride,
therapeutic options are now more limited.

Metoclopramide can be used, but in older adults, metoclopramide
frequently causes movement disorders including extrapyramidal symptoms
and tardive dyskinesia. These symptoms are similar in appearance to
Parkinson's disease and are sometimes irreversible even when the
medication is discontinued.

One recent study found that prescribers frequently confuse the
drug-induced side effects of metoclopramide with the onset of true
Parkinson's disease. In fact, older adults who take metoclopramide are
three times more likely to be placed on a medication for Parkinson's
disease.^2^ As a result, these patients are exposed to the risks of
unneeded drug therapy.

Erythromycin is another treatment approach.^3^ It does increase upper
gastrointestinal motility and is used for this purpose. But erythromycin
is an antibiotic. In this era of increasing concern about antibiotic
resistance, the fact that clinicians are using this approach is a clear
indication of the need for additional therapeutic options.

Cisapride is a prime example of a medication that was lost to clinicians
because of the weaknesses in the current system for safe use of
medications. It could be brought back onto the market with appropriate
safeguards to provide an additional therapeutic option where few are now
available.

### Multiple risk management programs are confusing

The various medication risk management programs currently used have each
been developed individually and separately. Each program is administered
separately, with different telephone numbers to call and requirements
for participation. The logistical challenges in obtaining the needed
information and authorization to prescribe, dispense or use these
medications present a significant barrier to access for these
medications in patients who could benefit from them.

### Restricting the source of supply for the drug product

Some of the tools and strategies used in existing risk management
programs have serious limitations and drawbacks. When patients are
required to obtain the restricted medication from only an exclusive
pharmacy provider, this segregates that particular medication from the
patient's usual source of supply for other needed medications. As a
result, any drug interactions involving the restricted medication will
be difficult to detect. The designated provider for the high risk
medication may attempt to collect information about other drugs in use
by the patient, but if the patient later needs a new medication, the
usual pharmacy provider may not detect the interaction with the
restricted medication.

Removing the local pharmacist from the loop with the restricted
medication also keeps the pharmacist from being able to assist the
patient with identification of possible adverse effects from the
restricted medication, or additive side effects with other medications
the patient may be taking.

Residents of nursing homes and assisted living facilities are usually
served by specialized long-term care pharmacies that provide needed
services such as specialized packaging, drug delivery, 24-hour emergency
service, and others. When special distribution programs exclude these
pharmacies from participation, these needed services, especially the
special packaging, are usually not available from the exclusive pharmacy
distributors. This creates significant logistical problems for the
long-term care facilities and increases the risk of medication errors.

### Prescriber restrictions

Restricting a medication to use only by physician specialists also
presents significant challenges for the patient. In some cases, patients
may have to wait for weeks or months to get an appointment with the
specialist to begin drug therapy. The specialist may also be
geographically distant from the patient, requiring substantial time and
effort to make the trip to the specialist. Finally, one assumption with
this approach is that the specialist will be knowledgeable about the
designated medication and strategies to minimize risk. Although this
assumption may generally be valid, this represents a potential hole in
the safety net.

Requiring prescribers to complete educational programs before
prescribing the medication may impose a significant burden on the
physician. If physicians choose not to prescribe the drug, this reduces
access to the medication by the patient, and forces the patient to go to
a different prescriber just for this specific medication.

### Prescription stickers

The strategy of having the prescriber place a special sticker on the
prescription to show that certain risk-management steps have been taken
has a number of problems. In the long-term care setting, traditional
prescription forms are seldom used. Prescribers may write prescription
orders in the medical record at the nursing facility, or telephone
orders from their office. Nursing homes have about 1.6 million
residents, and an additional 1-2 million persons reside in assisted
living or board and care homes. Any risk management approach must
consider the unique needs and requirements of these long-term care
settings. ASCP would be pleased to offer assistance to FDA in developing
or revising risk-management strategies to consider the special needs of
patients in these long-term care settings.

# New Risk Management Tools: Involving the Pharmacist

The existing menu of options used in risk management of medications has
failed to employ a key resource: the community pharmacist. In some
cases, the community pharmacy is bypassed altogether through exclusive
distribution arrangements with a single mail order pharmacy or a highly
restricted distribution network.

Involving the pharmacist as a key player in medication risk management
is highly desirable for several reasons. Pharmacists have, in fact,
always had an important role in managing risk of medications. Evaluation
of the appropriateness of the prescription by the pharmacist is the last
safety check before the medication reaches the patient. If the
pharmacist believes the medication dose may be too high or the
medication may interact with another drug the patient is already taking,
the prescriber will be alerted to ensure that the patient is not
inadvertently harmed.

Why not strengthen this structure and provide the pharmacist with tools
and resources to assist with managing risk of designated medications?
Existing risk management programs focus heavily on prescribers. The
United States has about 676,000 practicing physicians, plus many more
mid-level prescribers such as nurse practitioners and physician
assistants. Does it make more sense to focus resources and attention on
the nearly 1,000,000 prescribers or the 55,000 pharmacies where the
medications are obtained?

ASCP suggests that a voluntary network of participating pharmacies could
form the basis for a comprehensive medication risk management system.
This network would include any pharmacy willing to meet the program
guidelines. The pharmacist who dispenses the medication to the patient
would be responsible for ensuring that specific risk management
strategies are implemented. Education would be provided to the
pharmacist and documented to ensure adequate knowledge and skills for
performing the tasks.

Pharmacy-based risk management strategies could include:

-   Confirmation that drug interactions and contraindications to the
    medication do not exist. This would be conducted using standardized
    checklists and forms developed by a group of stakeholders, including
    the FDA, pharmaceutical manufacturer, prescribers, pharmacists, and
    other relevant parties.

-   Patient education, counseling, and/or training

-   Verification that needed laboratory tests have been conducted on
    schedule

-   Monitoring of the patient and reporting of adverse drug reactions to
    the prescriber, FDA and manufacturer

Long-term care pharmacies must be included in any pharmacy-based risk
management approach to ensure that the 3 to 4 million residents of
long-term care facilities have access to these medications when needed.

Pharmacy-based risk management is not the total answer to the issue, but
can be an important tool in a comprehensive risk management program.
Pharmacy-based risk management strategies may be adequate for some
medications. In other cases, additional strategies may be needed.

The advantages of the pharmacy-based approach are:

-   Prescriber restrictions can be eliminated or minimized, reducing the
    burden on prescribers

-   Consumers will have better access to the medication

-   The pharmacist, who has regular contact with the patient anyway, is
    enrolled in the effort to minimize risk from the targeted
    medications

-   A voluntary, but closed, network of pharmacies permits better
    oversight and accountability for use of high-risk medications

-   Allows concentration of limited resources on a smaller "target",
    since the number of pharmacies is relatively small compared to the
    number of prescribers

-   A pharmacy network can provide an infrastructure and starting point
    for management of high-risk medications. A common telephone number
    and web site could be developed for access to information about all
    the designated medications, reducing confusion and barriers to
    access to these medications.

The American Society of Consultant Pharmacists is pleased to have this
opportunity to provide input on medication risk management. We welcome
the opportunity to continue to discuss these issues with the FDA and
collaborate in the development or refinement of medication risk
management strategies.

For additional information, or questions about these comments, please
contact me or Thomas R. Clark, RPh, MHS, ASCP Director of Professional
Affairs; Telephone: 703-739-1316 x123; E-mail: tclark@ascp.com.

Thank you.

Sincerely,

![](media/image2.pct){width="2.748611111111111in" height="0.75625in"}

R. Tim Webster, ScD

Executive Director

# References

1\. Turnheim K. Drug treatment in the elderly: pharmacokinetic and
pharmacodynamic considerations. In: Mallarkey G. Drug treatment
considerations in the elderly. Auckland, New Zealand: Adis Books; 1999.

2\. Avorn J, Gurwitz JH, Bohn RL et al. Increased incidence of levodopa
therapy following metoclopramide use. JAMA 1995;274:1780-2.

3\. Janssens J, Peeters TL, Vantrappen G et al. Improvement of gastric
emptying in diabetic gastroparesis by erythromycin. N Engl J Med
1990;322:1028-31.