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The Clinician
The Outcome Resources Drug Information
Hospice Medication Utilization Trends: Part 2
Key Performance Indicators and Most Utilized Therapeutic Classes
Esther Liu, Pharm.D., MSIA
In our last issue of The Clinician, we identified sever al high-cost therapeutic classes using
average prescription claims data from our hospice client base. To extend the discussion, one of
the most utilized classes was selected for an in-depth cost analysis in this review, the opioid
analgesics . The cost analysis compared different medication options in order to identify the cost
-effective alternatives within the class. Some cost reduction strategy recommendations in terms
of medication selection are also provided in this review according to the cost analysis results
and the clinical nature of the therapeutic class. The cost per Rx presented in this review was
calculated based on the average cost of the actual claims data unless otherwise indicated. All
data collected for this review included medication claims processed from 01/01/2013 –
03/31/2013. The percentage, below, reflects the average aggregate cost for the opioid analgesic
category as a percentage of the total average drug cost for hospice clients of Outcome Resources:
In this issue
Hospice
1
Medication
Utilization Trends:
Part 2
C-diff. Treatment
in Hospice
Patients
Opioid Analgesics (29% of total average total hospice medication costs)
Opioid Analgesics
Opioid analgesics are the most utilized therapeutic class in hospice for pain control and terminal
shortness of breath. Opioid analgesic drugs are commonly categorized into short-acting and long
-acting products, and they can be used by themselves or more commonly in combination for
effective pain management. Most of the short-acting opioids that are commonly used in hospice
are cost-effective due to their generic availabilities, except for one product, oxycodone liquid
concentrate 20mg/ml. This product costs about $237/rx on an average prescription and it is
much more expensive than its sister alternatives, morphine concentrate ($29 per rx) and hydromorphone liquid ($44 per rx). On the other hand, most of the long-acting opioids are more expensive due to the lack of generic availabilities. The drug cost analysis for the long-acting opioids is presented in Table 1 and Graph 1. (page 2). Methadone was the most cost effective alternative ($11 per rx) among all long-acting opioids in our review. Methadone represented 26%
of the total prescription counts but only 4% of the total claim cost within the entire long-acting
opioid category. The second cost effective alternative identified was the morphine extended
release tablet ($49 per rx). Other products, such as fentanyl patch, Oxycontin and Opana ER
were all above $100 per rx for an average prescription. Although fentanyl patch has been generic for a while, this product is still quite expensive in comparison to methadone due to the high
cost associated with manufacturing a topical medication patch. As presented in Graph 1, the
utilization of methadone is comparable to the morphine ER tablet and fentanyl patch in terms of
prescription counts, which reflected the popularity of methadone use in the hospice setting for
pain control.
July 2013
Vol. 8
Issue: 3
3
Table 1 : Long acting Opioids Cost Analysis
Generic Drug Name
% Claim Cost
% Rx Count
Cost/Rx
Fentanyl Patch
54%
36%
$108
Oxycontin
22%
8%
$194
Morphine ER tablet
20%
30%
$49
Methadone
4%
26%
$11
Opana ER
0%
0%
$216
Graph 1: Long-acting Opioids Cost Analysis
Recommendations:

When selecting a short-acting opioid product, reserve oxycodone oral concentrate (20mg/ml) for those patients that cannot swallow tablets and are allergic or exhibit an intolerance to the cost-effective alternatives,
morphine and hydromorphone.

Consider methadone as the primary preferred long-acting opioid product due to its low cost and the comparable pain management outcomes for hospice patients. Methadone also comes in convenient dosage forms,
such as an oral concentrate (10mg/ml) that is still long-acting.

Reserve the expensive products, such as fentanyl patch, Oxycontin and Opana ER for those patients who
have experienced intolerable side effects or are allergic to the more cost-effective products, methadone and
morphine ER.
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The Clinician
Treatment of Clostridium difficile Infection in Hospice Patients
Julia Harder, Pharm.D., C.G.P.
Clostridium difficile (C. diff) infections are becoming more common and harder to treat, with a high risk of recurrence (25%
after the first episode and up to 65% after the second episode). Because C. diff infection most commonly affects older adults in hospitals or long-term care facilities, it is an illness that hospice care providers must be able to effectively manage.
Symptoms range from mild diarrhea to potentially life-threatening colonic inflammation. C. difficile is transmitted via the fecaloral route and is highly contagious. Universal precautions, including hand hygiene, barrier precautions (gloves), and environmental
cleaning are a must to prevent the spread of the organism. Antibacterial hand sanitizers do NOT kill C. diff spores.
C. diff infection is strongly associated with antimicrobial use. This is one reason why judicious use of antibiotics is important,
and why prophylactic antibiotics should be strongly considered for discontinuation when a patient is admitted to hospice. Antibiotics, especially broad-spectrum antibiotics, suppress the normal GI flora, which allows C. difficile to overgrow and cause infection.
Risk is increased by both longer exposure to antibiotics and exposure to multiple antibiotics simultaneously. Antibiotics most commonly implicated include clindamycin, penicillins, 2 nd and 3rd generation cephalosporins and fluoroquinolones – though just about
every antibiotic has been associated with C. diff. Importantly in hospice, chemotherapy (or other forms of immunosuppression) and
tube feeding also raise a patient’s risk of developing C. diff infection.
Treatment of C. diff infection is based upon whether the infection is the initial infection or a recurrence, and how severe the infection is. Guidelines from the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America
(IDSA/SHEA) grade severity based on three markers: age, peak white blood cell count and peak serum creatinine. According to the
guidelines, greater age has been consistently related to all adverse outcomes, probably due to a reduced immune response against C.
difficile and its toxins. However, the guidelines do not specify an age cut-off at which a patient should be considered as having a
severe or more complicated course versus a mild-to-moderate course. Leukocytosis (high white blood cell count) likely reflects the
severity of colonic inflammation; complications are more common among patients with a white blood cell count of 15,000 cells/
mcL or greater. An elevated serum creatinine (greater than or equal to 1.5 times the patient’s baseline) may indicate severe diarrhea
with subsequent dehydration or inadequate renal perfusion.
These guidelines may be useful for determining the severity of an infection in settings where labwork is routinely performed, such as in a hospital. But for hospice patients, in whom labwork is not routinely performed, we may need to rely on other
markers of severity, as recommended by the American College of Gatroenterology (ACG). These markers include:
Mild hypotension
Low-grade fever
Mental status changes
Abdominal tenderness
Evidence of declining renal function, such as lower-than-normal urine output
Patients with diarrhea and any of the above should be treated as having a severe infection. Patients with diarrhea and no other
signs or symptoms meeting the severe criteria listed above may be considered as having mild to moderate disease. For very severe
infections in which the patient will likely be admitted for intensive care (e.g., septic shock, ileus, toxic megacolon, renal failure),
treatment involves oral or rectal vancomycin in combination with IV metronidazole (this will not be covered further as this would
typically take place in a hospital setting).
First and foremost, the offending antibiotic suspected of causing C. diff infection should be discontinued right away. In
otherwise healthy individuals, simply discontinuing the offending antibiotic will resolve the diarrhea in up to 25% of patients. However, for hospice patients, who are of advanced age and not otherwise healthy, antibiotic discontinuation is not likely to result in
resolution and further treatment should be initiated.
Metronidazole and vancomycin are the long-standing agents of choice in the treatment of C. diff. Vancomycin is the only
agent with the FDA-approved indication of Clostridium difficile-associated diarrhea, and it has been shown in two studies to be
superior to metronidazole in the management of severe cases. However, the use of vancomycin for initial treatment of CDI markedly decreased following the 1995 Centers for Disease Control and Prevention’s recommendation that the use of vancomycin in hospitals be reduced, to decrease the selection pressure for the emergence of vancomycin-resistant enterococci. Vancomycin is also
more expensive than metronidazole. For these reasons, metronidazole is generally recommended as first-line therapy for C. diff
infection, with oral vancomycin being reserved for severe cases, patients who have had more than one recurrence, or patients in
whom metronidazole is ineffective, contraindicated or not well tolerated.
Prospective trials have not compared regimens with durations longer than 10 days. However, it is recognized that some
patients may respond slowly to treatment and may require a longer course (e.g., 14 days).
Recurrence (defined as another C. difficile infection within 8 weeks of completion of therapy) is common and can occur in
up to 25% of patients. In the case of the first recurrence, the same medication should be used as was used for the initial episode. For
patients who experience a second recurrence, vancomycin pulse therapy is recommended (metronidazole should not be used beyond
the first recurrence).
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Various vancomycin pulse therapy regimens have been used; IDSA/SHEA guidelines recommend: after the usual dosage of 125 mg
4 times per day for 10–14 days, vancomycin is administered at 125 mg 2 times per day for a week, 125 mg once per day for a week,
and then 125 mg every 2 or 3 days for 2–8 weeks. The rationale behind pulse therapy is that, while normal GI flora are being restored,
germinating C. difficile spores will be kept in check, and recurrence will hopefully be prevented. For a third recurrence after a pulsed
vancomycin regimen, fecal transplant should be considered, in which an infusion of stool from a healthy donor is given rectally. While
this may sound off-putting to patients and donors, it does seem to work quite well.
This chart summarizes the above recommendations and can be used to determine the most appropriate treatment for your patient:
Infection Characteristics
Treatment Regimen
Initial Occurrence
Mild to moderate infection
Severe Infection
First Recurrence
Second Recurrence
Third Recurrence
Metronidazole 500 mg PO TID for 10-14 days
If no improvement after 5-7 days of metronidazole therapy, switch to oral
vancomycin (125 mg PO four times daily for 10-14 days)
Vancomycin 125 mg PO four times daily for 10-14 days
Follow the same guidelines as for the initial occurrence (if metronidazole
was initially ineffective, go straight to vancomycin)
Oral vancomycin pulse regimen
IDSA/SHEA Regimen:
125 mg PO four times daily for 10-14 days,
Then 125 mg PO BID x 1 week,
Then 125 mg PO daily x 1 week,
Then 125 mg PO every 2-3 days for 2-8 weeks
ACG Regimen:
125 mg PO four times daily for 10-14 days,
Then 125 mg PO three times a week for 10 doses
Consider fecal transplant
Oral vancomcyin is commercially available in capsule form (125 mg and 250 mg strengths). However, the capsule form is very
expensive (average wholesale price (AWP) of approximately $31 per 125 mg capsule – that’s $1240 for a 10-day treatment course). A
less expensive and equally effective option that many institutions employ is to use the solution for injection, given orally. To prepare
the solution for injection for oral use, vials of vancomycin should be reconstituted using sterile water and then refrigerated with a 14day expiration. The patient then drinks the prescribed dose/amount. For example, a 1000 mg powder vial can be reconstituted with 20
mL of sterile water, and a dose of 2.5 mL (125 mg) given orally four times daily. Each 1000 mg vial will last 8 doses, or 2 days. Using
this approach reduces the cost substantially… the AWP for a 1,000 mg vial for reconstitution is about $5, which adds up to $25 for a 10
-day regimen (5 vials), or $35 for a 14-day regimen (7 vials). By comparison, the AWP for a 10-day course of metronidazole is about
$21; a 14-day course about $30.
Antidiarrheals such as loperamide (Imodium) and diphenoxylate/atropine (Lomotil) should NOT be used to treat C. difficileassociated diarrhea. Use of these agents can actually worsen the patient’s course. These agents treat diarrhea by slowing gastrointestinal
motility, which can prevent toxin elimination and worsen the intestinal damage caused by the C. diff toxins. Anion exchange resins,
such as cholestyramine (Questran)and colestipol (Colestid) can be used in combination with metronidazole, but should not be used in
combination with vancomycin, as they will bind to oral vancomycin and reduce its efficacy.
Probiotics are often given with antibiotics to treat or prevent C. diff, but there’s not enough evidence yet to prove that they
help. There is moderate evidence that two specific probiotics -- lactobacillus (Culturelle) and saccharomyces boulardii (Florastor) –
reduce the incidence of nonspecific antibiotic-associated diarrhea, but their role in the specific prevention of C. diff infection is not
clearly defined. For this reason, ISDA/SHEA guidelines do not currently recommend the use of probiotics as a preventative measure
against C. diff infection. There is only weak evidence supporting the use of saccharomyces boulardii in the treatment of C. diff infection, and neither set of guidelines (ISDA/SHEA or ACG) recommend probiotics for treatment of active C. diff infection. If probiotics
are used, keep in mind that they should be taken 2 hours AFTER an antibiotic to prevent interference with the antibiotic’s activity.
To read the guidelines:
IDSA/SHEA: http://www.jstor.org/stable/10.1086/651706
ACG: http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/
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