Download Evaluation of the Most Frequently Prescribed Extemporaneously

FEATURE
V E TE R I N A RY
I
Evaluation of the Most Frequently Prescribed Extemporaneously
Compounded Veterinary Medications
AT A LARGE INDEPENDENT COMMUNITY PHARMACY
Adel H. Karara, BPharm, PhD
Ryan Hines, PharmD
Zehra Demir, PharmD
Bethran Nnorom, PharmD
Robert Horsey, RPh
Geoffrey Twigg, PharmD, BCACP, CDE
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The authors’ affiliations are: Adel H. Karara, Associate
Professor, Department of Pharmaceutical Sciences, School of
Pharmacy, University of Maryland Eastern Shore, Princess
Anne, Maryland; Ryan Hines, Pharmacist, Walgreens,
Salisbury, Maryland; Zehra Demir, Pharmacist-in-Charge,
CVS, Marlton, New Jersey; Bethran Nnorom, Staff Pharmacist,
Safeway Pharmacy, Crofton, Maryland; Robert Horsey,
Pharmacist, Apple Discount Drugs, Salisbury, Maryland;
Geoffrey Twigg, Clinical Pharmacist, Apple Discount Drugs,
Salisbury, Maryland.
Introduction
Although there has been
an increase in the number
of approved veterinary
products on the market,
it is still well recognized
that extemporaneous drug
formulation is essential to
provide optimal pharmaceutical care to veterinary
patients, especially when
medications are not available in the desired dosage
form for optimum efficacy.
Lack of commercially available products; drug dose
adjustment; high cost of
finished drug products,
especially those for certain
neoplastic and immunemediated diseases; ease
of administration; and
International Journal of Pharmaceutical Compounding
Vol. 20 No. 6 | November | December | 2016
461
Veterinary
The lack of recent literature data on the most commonly
prescribed veterinary preparations was the main reason
for this investigation. Thus, the primary objective of this
study was to explore the variety of veterinary
prescriptions requiring extemporaneous compounding
at an independent pharmacy with extensive
compounding abilities.
A
Abstract
Extemporaneous drug formulation is essential to provide optimal
pharmaceutical care to veterinary patients. The need for this is exacerbated
by the fact that commercially produced veterinary-specific products, without
a human indication, require specialty veterinary manufacturing facilities
and a new animal drug application process to gain marketing approval. This
study examined the prescription patterns of extemporaneously compounded
veterinary preparations in the compounding department at a large independent
community pharmacy. Data was obtained from a total of 1348 prescriptions
requiring extemporaneous compounding over the course of a two-year period
(2014–2015). A database was constructed and each compounded prescription
was allocated to a therapeutic category based on the American Hospital
Formulary Service Drug Information. Data analysis showed that the most
commonly prescribed preparations belonged to the central nervous system
(39%), anti-infective agents (21%), and hormones (12%) therapeutic categories.
Overall, suspensions were the most dispensed (47%), extemporaneously
compounded dosage forms followed by solutions (28%), and capsules (10%).
The majority (88%) of compounded preparations were administered by the
oral route. The top three drugs that are compounded for veterinary medicine
were (1) potassium bromide oral solution for canine epilepsy, (2) methimazole
solution used to treat hyperthyroidism in cats, and (3) metronidazole
suspension, an antibiotic for the treatment of diarrhea and other infections in
dogs and cats. Remarkably, our findings are in good agreement with previously
published survey data on the top drugs that are compounded for veterinary
medicine. In the era of personalized medicine, veterinary extemporaneous
compounding for specialized needs will continue to play an important role
providing optimum therapy for veterinary patients.
462
International Journal of Pharmaceutical Compounding
Vol. 20 No. 6 | November | December | 2016
flavor compounding to make
medication taste better and
enhance compliance are
typically the main drivers
for veterinary compounding.1 Thus, drug compounding has always been a part of
veterinary medicine.2 Very
little information is available
in the literature regarding the
most frequently compounded
veterinary drug preparations.
A literature search on the topic
of “top compounded veterinary
preparations” did not yield any
hits.3 A regional survey of the
subscribers of the International Journal of Pharmaceutical
Compounding in 1999 reported
on the top ten veterinary
compounded preparations,
which included potassium bromide capsules, metronidazole
suspensions, and methimazole
liquid.4 A study by Gargiulo et
al,5 based on a survey of 200
randomly selected veterinarians in New Zealand, showed
that preparations which were
commonly compounded
included cyclosporine eye
drops, methimazole gels, and
potassium bromide solutions.
The report acknowledged the
importance of the role that
compounding plays in providing better therapy for the
veterinary patient.5 The lack
of recent literature data on the
most commonly prescribed
veterinary preparations was
the main reason for this investigation. Thus, the primary
objective of this study was to
explore the variety of veterinary prescriptions requiring
extemporaneous compounding
at an independent pharmacy
with extensive compounding
abilities, hereinafter referred
to as “the retail pharmacy.”
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Veterinary
Methods
The retail pharmacy has been in operation since 1971. They have
performed extemporaneous compounding on an as-needed basis
since that time. However, there was a substantial increase in the
number of patients serviced in the late 1980s. In 1992, the retail
pharmacy joined a professional compounding association (Professional Compounding Centers of America [PCCA]), built a dedicated
compounding lab, and was able to dedicate full-time pharmacists’
hours to extemporaneous compounding of medications due to the
need of this service in the local community. Today, multiple pharmacists and a full-time pharmacy technician staff the compounding lab
attached to the retail pharmacy. Aside from basic equipment, the lab
is stocked with a powder safe hood for weighing and manipulation of
powder chemicals. To maintain pharmaceutical elegance of creams,
ointments, and gels, the retail pharmacy uses an ointment mill and
Unguator mixing technology. The pharmacy is also equipped with
digital scales, tube sealers, and a convection oven.
The compounding records for veterinary preparations over the
time interval from January 2014 to December 2015 were entered into
a database that included:
For the purposes of this study, we evaluated the three most frequently prescribed therapeutic categories, and then listed the most
frequently compounded active pharmaceutical ingredient in these
individual categories. We were also interested in evaluating the
most commonly prescribed dosage forms, route of administration,
and animal species.
Results
Over the study time period, the pharmacy filled about 10,000
total extemporaneously compounded prescriptions when numbers
for all patients, human and animal, are considered. That number
included a total of 1,348 extemporaneously prepared veterinary
prescriptions, including refills, which were entered in the database and were grouped according to AHFS into 13 therapeutic
categories. The 1,348 prescriptions came from a total of 801 unique
prescriptions with the remainder being made up of ordered refills.
Most prescriptions were for canine (33%) and feline (32%) species.
Other animal species included:
• Guinea pigs
•Porcines
•Horses
• Dosage form
• Route of administration
• Dosing regimen
•Quantity
• Patient species
• Prescriber name
Each compounded prescription in the
database was allocated to a therapeutic category based on pharmacologic-therapeutic
classification in the American Hospital Formulary Service Drug Information (AHFS).6
The therapeutic categories classified by
the AHFS included:
•
•
•
•
•
Antihistamine drugs
Anti-inflammatory agents
Anti-infective agents
Autonomic drugs
Blood formation, coagulation, and
thrombosis
• Cardiovascular drugs
• Central nervous system (CNS)
agents
• Respiratory tract agents
• Gastrointestinal drugs
• Skin and mucous membrane agents
• Hormone and synthetic substitutes
•Vitamins
• Miscellaneous therapeutic agents
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• Rabbits
• Sugar gliders • Rodents
• Owls
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International Journal of Pharmaceutical Compounding
Vol. 20 No. 6 | November | December | 2016
463
Veterinary
FIGURE 1. Therapeutic categories of the most frequently prescribed
compounded preparations.
Blood Formation,
Coagulation, and Thrombosis
Antihistamines
1. CNS agents
2. Anti-infective agents
3. Hormone and synthetic substitutes
ANTI-INFECTIVE AGENTS
Medications belonging to the antiinfective category accounted for 17% of
all filled original prescriptions. Prescriptions containing metronidazole were
the most commonly prescribed medications, accounting for 6.4% of all filled
original prescriptions. This was followed
by doxycycline and itraconazole representing 4.2% and 1.9% of prescriptions,
respectively.
HORMONES AND
SYNTHETIC SUBSTITUTES
Medications belonging to this category accounted for 12% of all filled original
prescriptions. Prescriptions containing
methimazole were the most commonly
prescribed medications belonging to this
category accounting for 10.5% of all filled
original prescriptions. Diethylstilbestrol
accounted for 1.6% of prescriptions.
464
Phenobarbital
Pain
Diethylstilbestrol
Autonomic Drugs
Fluoxetine
Miscellaneous
Therapeutic Agents
CENTRAL NERVOUS
SYSTEM AGENTS
Medications belonging to the CNS
category were by far the most commonly
prescribed agents, accounting for 34% of
all filled original prescriptions. Liquid
prescriptions containing potassium
bromide were the most commonly prescribed medication accounting for 20%
of all filled original prescriptions. This
was followed by diazepam and fluoxetine
representing 2.8% and 1.7% of all prescriptions, respectively.
Tramadol
Vitamins
Itraconazole
Ursodiol
Gastrointestinal Drugs
Zonisamide
Cardiovascular Drugs
Gabapentin
Anti-inflammatory Agents
Tacrolimus
Hormones and
Synthetic Substitutes
Atenolol
Anti-infectives
Diazepam
Central Nervous System Agents
Piroxicam
0
10
20
30
% Total Most Commonly Prescribed Rx
40
Doxycycline
Prednisolone
Metronidazole
Methimazole
DOSAGE FORMS
Medications belonging
to the CNS category
Transdermal
•Suspensions
were by far the most
Powder
•Syrups
Syrup
commonly prescribed
•Solutions
Ophthalmic
•Powders
agents, accounting for
•CapsulesEnema
• Ophthalmic
solutions
Cream
34% of all filled original
•Transdermals
Capsule
•Suppositories
prescriptions. Liquid
•EnemasSolution
Suspension
prescriptions containing
Overall, the majority of compounded
0
10
20
30
40
50
potassium
bromide
were
preparations (75%) were
liquid dosage
forms. Suspensions and solutions account- % Total Rx
the most commonly
ed for 47% and 28% of all dosage forms as
illustrated in Figure 2. The top 4 dosage
prescribed medication
forms compounded were:
accounting for 20% of all
1. Suspensions
2.Solutions
filled original
3. Capsules
prescriptions.
4.Creams
Potassium
The prescriptions in the database conSuppository
tained the following dosage forms:
International Journal of Pharmaceutical Compounding
Vol. 20 No. 6 | November | December | 2016
f Administration
A summary of percentage of the most
frequently dispensed extemporaneous
prescriptions as a function of main therapeutic categories is displayed in Figure 1.
The top three most frequently prescribed
products belonged to the following therapeutic categories:
Oral
Topical
Rectal
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0
P
Synthetic Substitutes
0
10
Atenolol
Anti-infectives
Diazepam
Central Nervous System Agents
Piroxicam
0
10
20
30
20
30
40
50
Veterinary
% Total Rx
Doxycycline
40
Prednisolone
% Total Most Commonly Prescribed Rx
Metronidazole
Methimazole
FIGURE 3.
Route of drug administration.
Potassium
Route of Administration
FIGURE 2. Most frequently prescribed dosage forms.
Suppository
Transdermal
Powder
Syrup
Ophthalmic
0
Oral
5
10
15
20
25
Topical
Rectal
Ocular
0
50
Enema
100
150
200
250
300
350
Number of Rx
Cream
Capsule
Solution
Discussion
Suspension
0
10
20
30
40
50
% Total Rx
ROUTE OF DRUG
ADMINISTRATION
Extemporaneous compounding is historically one of the original methods of the practice of pharmacy. In today’s practice of
medicine, most prescriptions can be dispensed from commercially
available products. Extemporaneous compounding is a niche role
that some pharmacies fulfill. However, with the needs of special
Route of Administration
Orally administered dosage forms
constituted the majority of compounded
prescriptions as depicted in Figure 3, with
topical, rectal, and ocular accounting for a
small fraction of Oral
total prescriptions.
Topical
Rectal
TOP COMPOUNDED
DRUG
AGENTS Ocular
The top three drug agents that were
0
50
100
150
compounded for veterinary medicine were:
ARL Bio Pharma, Inc.
200
Number of Rx
1. Potassium bromide oral solution to
treat canine epilepsy
2. Methimazole solution to treat hyperthyroidism in cats
3. Metronidazole suspension, an antibiotic for treatment of diarrhea and
other infections in dogs and cats as
seen in Figure 4
Table 1 shows a comparison of the top
10 veterinary compounded preparations
based on a survey conducted in 19994 and
our current data. Although almost fifteen
years separate the two surveys, examination of the data show remarkable similarities, especially in the top three veterinary
compounded preparations.
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250
300
30
Percent of Most Frequently Compounded Drug Agents
350
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International Journal of Pharmaceutical Compounding
Vol. 20 No. 6 | November | December | 2016
465
Veterinary
Blood
Formation, such as hospice, pediatrics, and veterinary patients,
populations
oagulation, and Thrombosis
along with the prescribers desire to tailor medication regimens to
Antihistamines
specific
patient needs, extemporaneous compounding fills a major
gap inVitamins
the care of these patients.7 Extemporaneous compounding
is emerging
as a specialized area of pharmacy practice with the
Pain
emphasis on personalized and patient-centered health care. Sherr
Autonomic Drugs
and Karara have noted that it would be important for compounding
Miscellaneous to explore opportunities for marketing their services
pharmacies
Therapeutic Agents
to veterinary clinics in order to provide optimum care for the
Gastrointestinal
Drugs
veterinary
patient.8
In theDrugs
present study, the total number of veterinary prescripCardiovascular
tions (1348) provided enough volume to examine the prescription
Anti-inflammatory Agents
patterns of extemporaneously compounded veterinary medications
Hormones
at
a largeand
independent community pharmacy. Remarkably, our
Synthetic Substitutes
findings are in agreement with previously published survey data
Anti-infectives
on
the top drugs that are compounded for veterinary medicine.4
that the top three drugs that were compounded for
tral Nervous Davis
System reported
Agents
veterinary medicine were4:
0
10
20
30
1. Potassium bromide
% Total Most Commonly Prescribed Rx
2. Metronidazole suspension
3. Methimazole oral liquid
40
FIGURE 4. Most frequently compounded drug agents.
Tramadol
Phenobarbital
Diethylstilbestrol
Fluoxetine
Itraconazole
Ursodiol
Zonisamide
Gabapentin
Tacrolimus
Atenolol
Diazepam
Piroxicam
Doxycycline
Prednisolone
Metronidazole
Methimazole
This is in agreement with our data. It was interesting to note the
similarities as well as the differences in the older survey and our
data. There was very little change in the majority of the commonly
Suppository
prescribed drugs. The top three drugs in both lists contained:
Potassium
0
5
10
15
20
25
30
Percent of Most Frequently Compounded Drug Agents
Transdermal
1. Potassium bromide (for seizure prevention)
2. Methimazole (for hyperthyroidism)
Syrup
3. Metronidazole (for bacterial infections)
Powder
has gone up along with concerns of bone marrow suppression,
and hepatic monitoring requirement has caused this medication
to be a last-line therapy. It is also interesting to note that no pain
medications made the 1999 list, but two medications for pain—gabapentin and piroxicam—were included in our results. Piroxicam
also has an added indication in canine patients for bladder cancer.
Ophthalmic
Route of Administration
The use of diethylstilbestrol, commonly used for urinary
Enema
incontinence in spayed dogs, is no longer prescribed as often as
Cream
it had been; the amount of side effects and blood-work monitorCapsule
ing required has caused the drug to fall out of favor. Cyclosporine
used as an eye drop can no
Solution
longer be compounded due to
Suspension
TABLE 1. Comparison of the Top Ten Veterinary Compounded Preparations.
a usage patent. Since the Davis
4
publication,
this 10
chemical is
0
20
40 DATA PROVIDED
50
30
IN DAVIS J. COMPOUNDING FOR DATA FROM THIS 2014now available commercially. % Total Rx
RANKING CREATURES: WHAT WORKS. IJPC 1999; 3(3): 182–185 2015 STUDY*
The price of the commercial
1
Potassium bromide capsules Potassium bromide
product and the lack of pre2
Metronidazole suspension (various strengths)
Methimazole
scription insurance for most
3
Methimazole 5-, 10-, 100-mg/mL oral liquid Metronidazole
animals make this an impracti4
Diethylstilbestrol 0.5-mg, 1-mg, 2-mg, 3-mg, 5-mg capsules
Prednisolone
cal option for many pet owners.
5
Potassium bromide solution Doxycycline
In place of cyclosporine, we
6
Cyclosporine 2% ophthalmic solution Piroxicam
now typically use tacrolimus.
7
Prednisone
0.5-,
1-,
5-,
10-mg/mL
oral
liquid
Diazepam
Chloramphenicol, an inexpen8
Amitriptyline
5to
100-mg/mL
oral
liquid
Atenolol
sive broad spectrum antibiotic,
9
Chloramphenicol 150-mg/mL oral suspension
Tacrolimus
is not used as often as it was
Oral
10
Protamine zinc insulin, 10 to 100 units/mL
Gabapentin
back in 1999. Since that study,4
the rate Topical
of antibiotic resistance
*Active ingredients in different dosage forms and strengths.
466
Rectal
Ocular
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250
300
350
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Veterinary
A report by an
independent pharmacy shows that
top compounded
medications for
companion animals
were: aminopentamide, cisapride,
cyclosporine,
diethylstilbestrol,
methimazole,
metronidazole,
tacrolimus and
trilostane.9
Due to the
limitations in data
collections, not all
prescriptions contained the species
of the animal that
was being treated.
When this information was available, canines and felines made up the majority of
the animals. Some of the other animals that were serviced by the
pharmacy were:
• Guinea pigs
• Sugar gliders
•Birds
• Chinchillas
• Rodents
Limitations to the findings of our study related to the fact that it
was conducted at one site. While study findings are similar to that
of the cited 1999 study,4 it may not be representative of prescribing
habits in other locations. Also, the pharmacy where the study was
conducted has invested considerable resources on the infrastructure
of the compounding lab and on educating the public and prescribers
on the use and availability of extemporaneous-prepared formulations. This may not be typical for other community pharmacies that
provide compounded drug formulations to patients. We are hopeful
that this report would stimulate more research into the unmet compounding needs in the area of veterinary drug compounding.
Conclusions
Veterinary prescriptions belonging to the therapeutic categories
of CNS agents, anti-infective agents, and hormone and synthetic
substitutes were the three most commonly prepared extemporaneous medications. Overall, the most dispensed extemporaneously
compounded dosage forms were suspensions, solutions, and
capsules. Canine and feline patients were the most treated patients
seen by the pharmacy. Overall, veterinary compounding is a large
part of the compounding pharmacy’s workflow, making up approximately 15% of all the compounding prescriptions dispensed.
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Acknowledgment
The authors would like to acknowledge
Ms. Emanga Ekinde and Ms. Mineille
Gakuu both Student Pharmacists of the
Class of 2016 for their help with the prescription database.
References
SUGAR GLIDER
1.Karara AH. (2016). FDA draft guidance on
compounding animal drugs from bulk drug
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3. PubMed Literature Search. National Center for
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Veterinary Preparations. [NCBI Website.] Available at: www.ncbi.nlm.nih.gov/pubmed/?ter
m=Top+compounded+veterinary+preparations
accessed. Accessed on February 5, 2016.
4. Davis J. Compounding for creatures: What
works. IJPC 1999; 3(3): 182–185.
5. Gargiulo DA, Chemal C, Joda L et al. Extemporaneous compounding in veterinary practice: A
New Zealand prespective. N Z Vet J 2013; 61(6):
311–315.
6. McEvoy GK, ed. AHFS Pharmacologic—Therapeutic Classification. In: American Hospital
Formulary Service Drug Information. Bethesda,
MD: ASHP; 2007.
7. Nahata MC, Allen LV Jr. Extemporaneous drug
formulations. Clin Ther 2008; 30(11): 2112–2119.
8. Sherr Z, Karara AH. Evaluation of the most
frequently prescribed extemporaneously ccompounded medications in a rural setting: A case
study from the Delmarva Peninsula. IJPC 2014;
18(6): 462–468.
9. Scully P. Wedgewood Pharmacy. Top 15
Compounded Veterinary Medications for
Companion Animals and Horses: Veterinary
Compounded Medications that May be Prescribed for Companion Animals. [Wedgewood
Pharmacy Website.] June 27, 2011. Available
at: www.wedgewoodpetrx.com/blog/posts/
top-15-compounded-veterinary-medications-forcompanion-animals-and-horses.html. Accessed
February 5, 2016.
Address correspondence to Adel H. Karara,
B Pharm, PhD, Associate Professor, Department of Pharmaceutical Sciences, School of
Pharmacy, University of Maryland Eastern
Shore, 11868 Academic Oval, Princess Anne,
MD 21853. E-mail: [email protected]
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