Compounded Analgesics Relieve Pain from Arthritis, Neuropathy, Postpolio Syndrome

182
International Journal of Pharmaceutical Compounding

Vol. 14 No. 3 | May/June 2010
www.IJPC.com
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Abstract
Pain caused by disorders of move-
ment is often chronic and severe and
may not be alleviated by commer-
cially available medications. In such
cases, the use of a compounded for-
mulation can provide relief, either as
sole therapy or as part of a combi-
nation treatment regimen. In this re-
port, we review the effects of com-
pounded analgesic preparations on
chronic severe pain like that pro-
duced by arthritis, neuropathy, or
postpolio syndrome. Case reports
are included, formulations are pre-
sented, and two patients (one of
whom, RFM III, is a coauthor of this
paper) with a painful movement dis-
order describe their response to cus-
tom compounded therapy.
v
e
ARTHRITIS,
NEUROPATHIC
PAIN, AND
POSTPOLIO
SYNDROME
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isorders of movement that result from
arthritis, neuropathy, or postpolio
syndrome (PPS) compromise quality
of life, limit activity, and engender
chronic and often severe pain that
in some patients is refractory to
conventional treatment. Arthritis is
a disorder of protean manifestations:
More than 100 rheumatic conditions,
including osteoarthritis, rheumatoid
arthritis, lupus, fibromyalgia, and
gout, are among its various forms.
1
A recent issue of the Morbid-
ity and Mortality Weekly Report summarizes the findings of an
analysis, by the Centers for Disease Control and Prevention (CDC)
and the U.S. Census Bureau, of the most recent data from the Survey
of Income and Program Participation, which indicated that among
U.S. adults in 2005, arthritis and rheumatism were among the three
most common causes of disability.
2
Arthritis, which afflicts all racial
and ethnic groups, is common in adults aged 65 years or older, but
almost two-thirds of individuals with that disorder are younger than
that age.
1
The most common form of arthritis in the U.S. is osteoar-
thritis.
1
According to the CDC, 37.2 million white adults, 4.6 million
black adults, 3.1 million Hispanic adults, and 1.6 million adults of
other races in the U.S. have clinically diagnosed arthritis; blacks
with arthritis have more activity limitation than do whites with that
disorder; blacks and Hispanics with arthritis have more work limita-
tion and severe joint pain than do whites with arthritis; the risk of
arthritis is more common among women than men; and an estimated
294,000 children younger than 18 years have some form of arthritic
or rheumatic condition.
3

Severe chronic neuropathic pain, which is usually caused by
damage to peripheral nerve tissue from various physical, thermal,
or chemical agents, is difficult to relieve.
4
Because damaged nerves
send pain-sensing fibers into an area of the spinal cord in which
there are no mu or kappa
receptors, endogenous
endorphins and opioids
provide inadequate pain
relief.
4
Compounded
preparations, however,
can be formulated to in-
clude multiple nonopioid
analgesic agents that,
when topically applied,
safely relieve pain with-
out systemic effects or
the risk of addiction.
PPS, which can develop
years after recovery from
an initial acute attack of
poliomyelitis, is charac-
terized by new weakening
in muscles affected by
poliovirus and in muscles
that seemed to have been
unaffected by that dis-
ease.
5
The symptoms of
PPS include unaccustomed fatigue (both generalized and muscular),
slowly progressive muscle weakness, muscle atrophy, and pain from
joint degeneration and progressive skeletal deformity.
5
According to
estimates from the National Center for Health Statistics, more than
440,000 polio survivors in the U.S. may be at risk for PPS.
5
For many individuals who live with the types of pain described
above, commercially manufactured analgesic agents are unavailable
in the combinations, doses, or dosage forms necessary to enable safe
and adequate therapy. In this report, we present and comment on
the cases of patients whose pain from arthritis, neuropathy, or PPS
is successfully managed with a compounded preparation customized
to meet individual medical needs. A patient with PPS describes the
outcome of his treatment with a variety of compounded medications,
and formulations for several analgesic preparations are provided.
Pain from Arthritis and
Postpolio Syndrome
Brian Erickson, MD
Center for Pain Medicine
Fletcher Allen Health Care
Burlington, Vermont
I am a psychiatrist and a specialist in pain management. In ad-
dition to treating the emotional challenges faced by patients with
severe chronic pain, I often prescribe opioids, other analgesic
medications, and physical therapy to combat the physical impair-
ment produced by unremitting pain. My patients range in age from
children to the elderly; some are employed, and others are disabled.
They are referred to me by other physicians when pain caused by a
rheumatologic disorder such as arthritis significantly impairs their
function. On a pain scale of 1 to 10 (where 10 represents the worst
possible pain), many of my patients pain scores range from 5 to 9
when they are first evaluated. Ineffectively treated pain of that in-
tensity produces significant depression and emotional stress. Patients
so afflicted experience a significantly diminished quality of life;
some lose their role in their family, and their ability to work is often
compromised.
Most of my patients with chronic pain have received prior treat-
ment with anesthetic injections or oral nonsteroidal anti-inflam-
matory medications, steroids, or opioids, all of which have proven
ineffective in providing relief. However, a compounded transdermal
form of a specific drug often provides effective analgesia for patients
in whom the oral drug produces adverse effects or the effective oral
analgesic dosage would be too high to permit safe therapy.
For more than 10 years, I have prescribed compounded medica-
tions to relieve pain. I rely greatly on compounding pharmacist Scott
Brown, who is extremely helpful in researching the literature and
developing innovative preparations to meet patients needs. He is an
excellent problem solver, and I enjoy collaborating with him very
much.
Among the factors that guide treatment for chronic pain are the
level of the patients functional impairment (for example, whether
Feature
Scott Brown, RPh
Custom Prescription Shoppe
South Burlington, Vermont
Brian Erickson, MD
Williston, Vermont
George Muller, RPh
Compounding Corner
Madisonville, Louisiana
Susan J. Bryant-Snure, MD
North Institute
Lacombe, Louisiana
Richard F. Mestayer III, MD
Stress Treatment Unit
Ochsner Clinic
New Orleans, Louisiana
D
184
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pain afects the enjoyment of hobbies or social activities) and whether he
or she can perform activities of daily living, move around the house, and
provide self-care. I often prescribe compounded transdermal gels or creams
to treat local inammation caused by rheumatoid arthritis or osteoarthritis
(the types of arthritides that are most common in my practice) and to obvi-
ate the need for oral systemic analgesics, which can cause adverse efects or
may not be as efective as a customized formulation. Typically, rheumatoid
arthritis, which is a systemic autoimmune disease, produces inammation
Preparation Details, Application, Mechanism of Action
Applied locally; after a month of initial therapy, the ketoprofen concentration can
be increased to 15%, and this preparation can be used long term. By reducing the
level of cyclooxygenase-2 enzymes, it relieves inammation and provides analgesia
without oral ingestion, which can result in ulcers and adversely affects the liver and
kidneys.
Antidepressants exert a direct effect on neuropathic pain and improve the effects of
other analgesic agents. It appears that oral amitriptyline inhibits upcoming pain sig-
nals in the descending pain pathway that travels from the brain down the spinal cord,
but many patients cannot tolerate the weight gain or the anticholinergic and antihis-
taminic effects associated with oral amitriptyline therapy. When applied in a cream to
areas of arthritic or neuropathic pain, amitriptyline is an extremely effective analgesic.
This preparation ameliorates chronic pain (especially that with a neuropathic compo-
nent) by improving peripheral nerve conduction up to the level of the spinal cord.
A preparation used to treat muscle spasms that develop in response to myofascial
pain.
This preparation can be used alone or in combination with other agents to relieve
chronic, sharp, burning neuropathic pain; trigeminal neuralgia; or temporomandibu-
lar joint pain (which is considered a type of arthritis) by affecting N-methyl-D-aspar-
tate (NMDA) receptors. Nasally applied ketamine can relieve the pain from migraine
headache.
A preparation used to treat the pain from muscle spasms or low back pain. Baclofen
suppositories are effective in relieving spasms of the pelvic oor.
Commercially available oral hydrocodone is usually combined with acetaminophen,
but hydrocodone without acetaminophen can be prepared in a compounded medica-
tion.
This drug can be added to opioids to minimize opioid-induced hyperalgia.
A preparation that can be formulated as a nasal spray that provides effective analge-
sia at a lower dose than that required for oral treatment.
This preparation can be used to treat pain from shingles, neuromas, arthritis, and
other forms of nerve damage.
This preparation can be used to prevent migraine headache.
Now considered a hormone, vitamin D is administered to patients who are decient
in that vitamin.Vitamin D is absorbed instantly when injected. Although its mecha-
nism of action is unclear, it positively affects pathways for both pain and depression.
The Framingham study showed that osteoarthritis of the knee progressed more rap-
idly in individuals with 25(OH)D levels lower than 36 ng/mL,
6
and Lane and colleagues
demonstrated that osteoarthritis of the hip progressed more rapidly in individuals
with 25(OH)D levels lower than 30 ng/mL.
7
Information about vitamin D that is of
interest to compounders can be found at these websites:
http://pain-topics.org/clinical_concepts/vitamind.php#VitDPPM
www.pharmwell.com/index.htm
http://grassrootshealth.net/
Oxytocin modulates the level of nitric oxide (a substance implicated in the elevation
of chronic pain levels), augments the positive effects and duration of opioids, reduces
emotional stress, and relieves depression.
Compounded Preparation
Ketoprofen 10% in Lipoderm
Amitriptyline 2% in Lipoderm
Gabapentin 6% to 10% in
Lipoderm
Magnesium chloride 10% in
an emollient cream
Ketamine 5% to 10% in
Lipoderm
Baclofen 2% in Lipoderm
Oral opioids in various
strengths
Low-dose oral naltrexone
Hydromorphone and other
opioids
Bupivacaine 1% to 4% in
Lipoderm
Lidocaine 4% in a nasal spray
Vitamin D 100,000 U for
injection
Oxytocin in a nasal spray or a
sublingual troche
Feature
TABLE. List of Transdermally or Nasally Applied Compounds for the Treatment of Pain and Motion Disorders.
185
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Rx
OXYTOCIN 5-U/0.1-ML NASAL SPRAY
For 30 mL
METHOD OF PREPARATION
1. Calculate the required quantity of each ingredient for the total
amount to be prepared.
2. Weigh and/or measure each ingredient accurately.
3. Combine the glycerin with 10 mL of preserved water in a precali-
brated beaker.
4. Spin the mixture from step 3 for 1 minute and then add the oxy-
tocin.
5. Spin the mixture from step 4 until the oxytocin aliquot has com-
pletely dissolved.
6. Package and dispense.

PACKAGING
This preparation should be dispensed in a 1-oz white opaque bottle
that has a metered nose-spray pump.
LABELING
One spray in one nostril 3 times daily. Keep refrigerated.
STABILITY
A beyond-use date of 90 days can be used for this preparation.

STORAGE
Store in a refrigerator.
USE
For the treatment of chronic pain.
Source: Scott W. Brown, RPh, Custom Prescription Shoppe, South Burlington,
Vermont
Glycerin 0.6 mL
Oxytocin aliquot 0.542 U/mg 2.802 g
Preserved water qs 30 mL
Feature
and deformation of the smaller joints, but osteoarthritis is a mechanical
disorder of motion in which either overuse or inadequate cartilage results
in wear and tear on weight-bearing joints over time.
I usually prescribe the transdermally or nasally applied compounds that
are listed in the accompanying Table, some of which can be formulated in
combination, to relieve pain from a variety of causes, including disorders
of motion.
Many insurance plans do not cover the cost of compounding the
preparations listed in the Table, which is unfortunate for patients who nd
commercially available treatment inefective. One of my patients, whose
therapy is described in more detail in the rst case report, experienced
severe chronic temporomandibular joint pain that was signicantly relieved
by a transdermal combination of ketoprofen, amitriptyline, and gabapentin.
Opioid therapy was contraindicated for that individual. The cost of the
analgesic compound was covered by her health insurance plan until her in-
surance benets were modied. Then, the only therapeutic option was that
of prescribing and eventually increasing the dosage of opioids (a relatively
more expensive treatment that resulted in adverse efects and negatively
afected this patients social situation).
The use of a transdermal analgesic preparation can reduce the need for
additional medications such as opioids and is of benet to patients who
cannot tolerate oral therapy. Transdermal preparations are also useful
in iontophoresis for the treatment of tendinitis and lateral epicondylitis.
There is no question that for the patient described in the rst case report
below, a transdermal compound proved safe, tolerable, and efective in
relieving severe chronic pain when no commercially manufactured product
provided adequate relief.
Case Report
: : NUMBER 1 : :
In 2005, a 35-year-old white female patient with temporomandibular
joint pain and posttraumatic stress disorder was referred by her dentist
to our pain management practice. At that time, her pain score was 9 on
a 10-point pain scale in which a score of 10 represents the worst pos-
sible pain. Her discomfort increased when she ate or spoke, and pain
profoundly and negatively afected her quality of life. At the time of
presentation to our clinic, she was unable to work because eating and
talking were excruciating, her chronic pain had become debilitating, and
her social life had been adversely afected. She was being treated with
oral duloxetine and high doses of oral oxycodone. That treatment was
efective but produced intolerable adverse efects. A prior trial of oral
gabapentin had proven inefective.
To treat this patients temporomandibular joint pain, I prescribed
a transdermal compound of ketoprofen 10%, amitriptyline 2%, and
gabapentin 4% in Pluronic lecithin organogel (PLO). Over time, the
concentration of ketoprofen was increased to 15%, and the efcacy of
the compound then improved. The patient was instructed to apply, while
wearing gloves, a sufcient amount of the cream over the afected area
and around her jaw 3 times daily. Within 2 weeks after the initiation
of that therapy, the pain had resolved to a manageable level. She was
reevaluated at 8-week intervals during the 2-year duration of treatment
with that preparation, which relieved her pain signicantlywithout
systemic afects or the risk of addictionand enabled her to address
other problems in her life. However, this patients insurance coverage
changed and disallowed reimbursement for that therapy. Because she no
longer has access to that compound, the likelihood of efectively manag-
ing her pain has diminished.
Scott Brown, RPh
Custom Prescription Shoppe
South Burlington, Vermont
Case Report
: : NUMBER 2 : :
C. S., a white male patient who is 65 years old at the time of this
writing, was aficted with polio when he was 6 years old. After his
recovery, his overall health was relatively good until he was in his early
50s. In 2006, at the age of 62, he was referred to our practice by Dr.
Brian Erickson to obtain an oxytocin nasal spray to treat depression and
compounded acetaminophen-free hydrocodone capsules for the treat-
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ment of severe chronic pain caused by PPS, rheumatoid arthritis, and
osteoarthritis. At that time, he was continuing to experience progressive
musculoskeletal and joint pain, fatigue, and loss of muscle strength of 10
years duration.
In addition to the compounded therapy described above, other
currently prescribed medications for this patient include bupropion,
buspirone, hydrocodone with acetaminophen (Vicodin) capsules,
intramuscular injections of testosterone, and oral sh oil and B vitamins.
Because C. S. is treated with Vicodin (which provides insufcient pain
relief when given as the sole analgesic agent), the 10-mg hydrocodone
capsules that we prepare for him do not include acetaminophen to en-
sure that his ingestion of that agent does not exceed the safe daily limit.
According to this patient, the compounded oxytocin nasal spray that we
prepare, which exerts more of an antidepressant than an analgesic efect,
is very efective in relieving the depression brought about by his chronic
pain. For C. S., we also compound a ketoprofen topical gel that provides
efective analgesia when hydrocodone provides insufcient pain relief or
a particular joint is very painful. In addition, we prepare quinine 325-mg
capsules to treat his diagnosed restless leg syndrome, and we carefully
monitor his treatment regimen to prevent the adverse efects of poly-
pharmacy. Because none of the medications that we prepare for C. S. is
available in a dosage or form that provides safe and sufcient analgesia in
his particular case, compounded medications provide the only alterna-
tive for long-term safe and efective pain relief.
Rx
HYDROCODONE 10-MG CAPSULES
For 100 capsules
3. Blend the powders geometrically.
4. Encapsulate the blended powders into size No. 1 capsules.
PACKAGING
Package the capsules in a light-resistant vial.
LABELING
May cause drowsiness. Avoid operating a motor vehicle after taking
this medication.
STABILITY
A beyond-use date of 180 days can be assigned to this preparation.
STORAGE
Store at room temperature.
USE
For the treatment of chronic pain.
Vermont
Hydrocodone bitartrate 1.0 g
Lactose monohydrate 36.6 g
Food color (powdered) 0.1 g
Rx
AMITRIPTYLINE 2%, GABAPENTIN 4%,
KETOPROFEN 10% IN LIPODERM
For 60 g
Amitriptyline 1.2 g
Gabapentin 2.4 g
Ketoprofen 6.0 g
Ethoxydiglycol 3 mL
Lipoderm qs 60 g
1. Calculate the required quantity of each ingredient for the
total amount to be prepared.
3. Tare an empty electric mortar and pestle jar on an electronic
balance.
4. Add the amitriptyline, gabapentin, and ketoprofen powders to
the tared electric mortar and pestle jar.
5. Wet the powders with sufficient ethoxydiglycol to make a
paste.
6. Add sufficient Lipoderm to the mixture from step 5 to reach
the final weight of the formulation.
7. Blend the mixture from step 6 with an electric mortar and
pestle.
8. Run the mixture from step 7 through an ointment mill 3 times.
9. Finish the preparation by mixing the mixture from step 7 with
an electric mortar and pestle.
PACKAGING
Package in an ointment jar or in topical syringes.
LABELING
For external use only.
STABILITY
A beyond-use date of 30 days can be assigned to this preparation.
STORAGE
USE
For the treatment of joint pain.
Vermont
Feature
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A Patients Testimony of Pain Relief
For more than 10 years, Ive experienced joint and muscle pain caused by a
combination of postpolio syndrome, osteoarthritis, and rheumatoid arthritis. I am
a woodworker. My pain is so severe that I couldnt stand living without effective
analgesic treatment because almost all physical activity would be impossible.
Ive found compounded preparations to be very effective in controlling my pain
level and safer than prescription drugs available from a retail pharmacy because
compounds can be customized. For example, every manufactured form of oral
hydrocodone contains other ingredients, such as acetaminophen, that would be
harmful in the daily intake required to manage my severe pain. Dr. Brian Erickson,
my pain management physician, has prescribed many commercially available
analgesics for me, but all of those products have one signicant drawback or
another, such as producing side effects like constipation or drowsiness, and they
are not as effective as the compounds I now use. My customized medications
allow me to be more comfortable day to day, and on a pain scale of 1 to 10, they
reduce my pain level from a denite 10 to about a 5. My current pain regimen,
which includes compounded preparations, enables me to enjoy activities that
are both pleasurable and possible, such as bicycling, and to live a normal life
without the limits that severe pain imposes. C. S.
Feature
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Pain from Degenerative Disc
Disease
Susan J. Bryant-Snure, MD
North Institute
Lacombe, Louisiana
Case Report
: : NUMBER 3 : :
P. D., a 42-year-old white male patient, sought my help for the
treatment of a disabling work-related lower back injury (an annulus
propulsus tear), the primary characteristics of which are low back
discomfort with limited range of motion, muscle spasm, and intractable
chronic pain. On a pain scale of 1 to 10 in which a score of 10 represents
the worst possible pain, his pain score was 8 at the time of presentation.
Comorbid conditions included hypertension, an abdominal hernia that
was also work related, and hiatal hernia. Prior treatment with a variety
of oral analgesic agents was inefective in alleviating this patients pain
and had produced adverse efects.
P. D. was experiencing myofascial pain caused by his disc injury and
characterized by muscle spasm and irritation of the dorsal spinal nerves
associated with the nerve roots near the injured disc. I often prescribe
a compounded topical preparation for patients who experience adverse
efects (gastroesophageal reux, excessive sedation) from treatment
with typical anti-inammatory medications or muscle relaxants, both of
which are helpful for this patient. A transdermal preparation of ketopro-
fen 10%, baclofen 10% in PLO was initially prescribed to be applied in
a dose of 1 mL twice daily. In October 2008, the concentration of both
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For most patients who have been treated with multiple failed pain-
treatment regimens, I suggest beginning customized therapy with a
combination of ketoprofen, lidocaine, gabapentin, and clonidine in
Rx
KETOPROFEN 5%, BACLOFEN 5% IN
PLURONIC LECITHIN ORGANOGEL
For 60 mL
Note: The Skin So Soft is a product of Avon Products, Inc., New York, New York.
3. Triturate the ketoprofen, baclofen, and NDMSO in a mortar.
4. Add the ethoxydiglycol to the mixture from step 3 and triturate to
a smooth paste.
5. Place the lecithin:isopropyl palmitate in the mortar containing
the mixture from step 4 and mix thoroughly. Add the Skin So Soft
to mask the odor of that mixture.
6. Add the Pluronic F-127 20% gel to the mixture from step 5 in
increments and mix well. A smooth, even gel should form.
7. Pass the mixture from step 6 through an ointment mill.
8. Dispense the preparation in an appropriate-size syringe with a
Luer-to-oral connector and several 1-mL topical syringes.
PACKAGING
Dispense this preparation in a 60-mL or two 30-mL syringes with a
Luer-to-oral adapter and several 1-mL topical syringes.
LABELING
To stimulate blood ow, use a towel to rub the area to be treated.
While wearing gloves, apply 1 mL topically twice daily as needed;
then wash hands. To enhance the penetration of the gel, cover the
treated area for 1 hour.
STABILITY
STORAGE
Store at room temperature. Do not store in the refrigerator or the
preparation may liquefy.
USE
To relieve the pain from degenerative spinal disc disease.
Source: George Muller, RPh, Compounding Corner, Madisonville, Louisiana
Ketoprofen 3 g
Baclofen 3 g
Decyl methyl sulfoxide (N) (NDMSO) 300 mg
Ethoxydiglycol 6 mL
Skin So Soft 10 drops
Lecithin:isopropyl palmitate solution 14 mL
Pluronic F-127 20% gel qs 60 mL
Feature
agents was reduced to 5%. That preparation continues to enhance the
results of concomitant treatment with the following therapy: metha-
done 10-mg tablets tid; oxycodone and acetaminophen (Percocet)
10/325 tid; a lidocaine patch 5% (Lidoderm) applied topically every
12 hours prn; promethazine (Phenergan) 25-mg tablets, one-half to 1
tablet daily prn only; and trigger point injections and steroid injec-
tions as needed (typically quarterly). The addition of a compounded
analgesic transdermal gel to the patients treatment regimen produced
rapid pain relief from muscle spasm and muscle pain, reduced the
frequency of necessary trigger point injections, produced fewer oral
drug interactions, and enabled a more potent dose of analgesics while
preventing adverse efects. At the time of this writing and with the
therapy described above, P. D.s pain level on a scale of 1 to 10, where
10 represented the worst possible pain, was about 3.
This patient is reevaluated at 3-month intervals if his condition
remains stable, and the ketoprofen-baclofen gel remains an essential
component of his treatment regimen. His long-term prognosis depends
on the benet of surgical intervention, but the use of a customized
analgesic gel is an efective tool in the armamentarium for providing
pain relief.
George Muller, RPh
Compounding Corner
Madisonville, Louisiana
Case Report
: : NUMBER 3 CONTI NUED : :
In May 2004, we rst compounded a transdermal analgesic gel (keto-
profen 10%, baclofen 10% in PLO) to relieve the pain from degenera-
tive disc disease for P. D., an adult male patient of Dr. Susan Bryant-
Snure. In October 2008, the concentrations of those compounded
agents were reduced to ketoprofen 5%, baclofen 5%, and that formula-
tion has remained unchanged because the patient continues to nd this
treatment very efective. However, the ketoprofen-baclofen formulation
that we prepare for P. D. can be modied to include clonidine (a central
alpha-agonist), gabapentin (a gamma-aminobutyric acid [GABA] ana-
logue), and/or amitriptyline.
Unlike opioids, the combination of ketoprofen and baclofen relieves
the burning or lancinating sensation that is characteristic of chronic
neuropathic pain, some causes of which are injury, surgery, ischemia,
cancer, an adverse reaction to a drug, compression, chemotherapy,
alcoholism, inammation, or various diseases such as diabetes, multiple
sclerosis, and infection with the human immunodeciency virus. The
pathway for acute pain perception has been described in detail by
McNulty.
8

Analgesic transdermal preparations must be compounded in a vehi-
cle that is a penetration enhancer, such as a lecithin:isopropyl palmitate
solution (Lipoil, motor oil), to ensure that they are efective. Most
transdermal analgesics penetrate the area of treatment and provide
relief within 20 minutes after they have been applied. Cream vehicles,
which are water soluble, are usually not used for such preparations,
with the exception of a capsaicin-containing formulation. Typically, the
agents in transdermal analgesics are efective in lower concentrations
than those required for oral therapy.
189
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Feature
Compounders must be vigilant in conrming the concentrations of
the analgesics prescribed. We suggest that patients try a prescribed an-
algesic compound for 30 days to determine its efcacy, and we counsel
them about the treatment regimen and remain available to answer ques-
tions or contact the prescriber if a modication of the formula seems
necessary.
Customized transdermal gels provide great variability in the
combinations of agents that can be administered in a single applica-
tion, and they prevent the adverse systemic efects often caused by oral
analgesic therapy. We have found repeatedly that for patients with pain
(particularly localized pain) that does not respond to treatment with
conventional drug regimens, a compounded transdermal preparation
will provide needed relief.
Rx
LECITHIN:ISOPROPYL PALMITATE
SOLUTION
For 220 mL
Sorbic acid 0.66 g
Lecithin soya (granules) 100 g
Isopropyl palmitate 117 mL
3. Disperse the lecithin and the sorbic acid in the isopropyl
palmitate.
4. Allow the mixture to stand overnight.
PACKAGING
Store in a tightly closed amber stock bottle.
LABELING
STABILITY
A beyond-use date of 180 days is recommended for this preparation.
STORAGE
USE
Pharmaceutical necessity.
Rx
PLURONIC
20% GEL WITH 5% UREA
For 100 mL
Urea 5 g
Pluronic F-127 granules 20 g
Potassium sorbate 0.3 g
Water, puried qs 100 mL
Note: Pluronic F-127 is poloxamer 407.
3. Dissolve the urea in the previously refrigerated puried water.
Use an amount of puried water that is approximately 75% of
the nal volume.
4. Add the potassium sorbate and the poloxamer 407 to the mixture
from step 3.
5. Bring the mixture from step 4 to the nal volume by adding the
refrigerated puried water. Refrigerate after all the poloxamer
407 granules have been wetted. Note: Complete dissolution may
require 24 hours or more under refrigeration.
PACKAGING
Store in an amber container in the refrigerator. This preparation
will solidify at room temperature.
LABELING
Keep refrigerated.
STABILITY
A beyond-use date of 6 months can be assigned to this preparation.
USE
PLO. We have found the following concentrations of those agents to be
efective: ketoprofen, 20%; lidocaine, 6%; gabapentin, 10%; and cloni-
dine, 0.2%. We recommend limiting the concentration of clonidine to
0.2% and that of lidocaine to no more than 10%. This combination
compound exerts a sodium-channel stabilizing efect by blocking the
transfer of sodium through the -amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid (AMPA) receptor gate, a process that down-
regulates pain. The pain of patients with chronic back or joint pain,
posttherapeutic neuralgia, complex regional pain syndrome, or diabetic
neuropathy responds particularly well to this preparation because each
of those disorders is perpetuated by NMDA and/or AMPA receptor
action.
We have found that localized pain usually resolves more quickly
after treatment with a transdermal compound as opposed to an oral
systemic analgesic medication. A transdermal gel can be applied
directly over the spinal cord if the afected area is covered by nerves
originating in a particular area (dorsal, lumber, or cervical) of the spinal
cord. If systemic circulation is the intended outcome, then the gel can
be applied to the inner wrist and (preferably) covered with an occlu-
sive dressing. The compounder must be aware, however, that adverse
systemic efects can occur if the wrist application site is used.
191
www.IJPC.com
Rx
PLURONIC 35% GEL WITH 5% UREA
For 100 mL
Urea 5 g
Pluronic F-127 granules 35 g
Potassium sorbate 0.3 g
Water, puried qs 100 mL
Note: Pluronic F-127 is poloxamer 407.
3. Dissolve the urea in the previously refrigerated puried water.
Use an amount of puried water that is approximately 75% of the
nal volume.
4. Add the potassium sorbate and the poloxamer 407 to the mixture
from step 3.
5. Bring the mixture from step 4 to the nal volume with the re-
frigerated puried water. Refrigerate after all the poloxamer 407
granules have been wetted. Note: Complete dissolution may require 24
hours or more under refrigeration.
PACKAGING
Store in an amber container in the refrigerator. This preparation will
solidify at room temperature.
LABELING
Keep refrigerated.
STABILITY
A beyond-use date of 6 months can be assigned to this preparation.
USE

Rx
KETOPROFEN 20%/GABAPENTIN 10%/
CLONIDINE 0.2%/LIDOCAINE 6% IN
PLURONIC LECITHIN ORGANOGEL
For 100 g
Ketoprofen 20 g
Gabapentin 10 g
Clonidine hydrochloride 0.22 g
Lidocaine 6 g
Ethoxydiglycol 4 mL
Krisgel 100 4 mL
Lecithin:isopropyl palmitate solution 22 mL
Pluronic F-127 gel 35% qs 100 g
Note: In the formulation above, clonidine hydrochloride 1.1 mg yields clonidine
1 mg and Pluronic F-127 is poloxamer 407.
3. Warm the ethoxydiglycol and add the ketoprofen gradually so that
a thick liquid solution results. Do not allow the mixture to change
colors; warm it at low heat.
4. Triturate the clonidine, gabapentin, and lidocaine together. Add
the liquid from step 3 to the powders with mixing. The result is a
suspension.
5. Add the lecithin:isopropyl palmitate to the mixture from step 4
and mix until a smacking sound occurs.
6. Add the Pluronic F-127 gel in small increments. Note: The amount
of lidocaine in this formulation tends to break the gel, which can be avoided
by adding Krisgel 100 as a thickening agent.
7. Add the Krisgel to the mixture from step 6.
8. Pass the resultant mixture through an ointment mill.
PACKAGING
Dispense this preparation in an appropriate-size syringe or syringes
with a Luer-to-oral adapter and several 1-mL topical syringes.
LABELING
Apply 1 mL topically to the afected area up to 4 times daily.
STABILITY
STORAGE
Store at room temperature. Do not store in a refrigerator or the
preparation may liquefy.
USE
To relieve neuropathic pain.
Pain after Spinal Fusion
Richard F. Mestayer III, MD
Medical Director Emeritus
Stress Treatment Unit
Ochsner Clinic
New Orleans, Louisiana
Case Report
: : NUMBER 4 : :
I am a psychiatrist and pain management specialist, and I also treat
patients for addiction and substance abuse. Despite having undergone
Feature
192
www.IJPC.com
of vitamin D to progression of osteoarthri-
tis of the knee among participants in the
Framingham Study. Ann Intern Med 1996;
125(5): 353359.
7. Lane NE, Gore LR, Cummings SR et
al. Serum vitamin D levels and incident
changes of radiographic hip osteoarthritis:
A longitudinal study. Study of Osteoporo-
tic Fractures Research Group. Arthritis
Rheum 1999; 42(5): 854860.
8. McNulty JP. Levorphanol for the treat-
ment of severe chronic pain. IJPC 2007;
11(3): 202211.
For additional information, contact Scott W. Brown,
RPh, Custom Prescription Shoppe, 42 Timber Lane,
South Burlington, VT 05403, E-mail: scott@
customrxshop.com; Brian Erickson, MD, 4185
St. George Rd, Williston, VT 05495, E-mail:
beatoca@aol.com; Susan J. Bryant-Snure, MD,
29301 Dixie Ranch Rd, Lacombe, LA 70445; George
Muller, RPh, Compounding Corner, 2098 Covington
St, Madisonville, LA 70447, E-mail: compound-
ingcorner614@yahoo.com; or Richard F.
Mestayer III, MD, 32900 Pitcher Road, Springeld,
LA 70462.
a 3-level spinal fusion involving a pelvic
autograft in 1992, when I was 43 years of age,
I still experience moderately severe, aching,
chronic back pain from degenerative disc
disease. It is my overall strategy, for my patients
and my own treatment, to avoid systemically
active analgesics to treat pain. For the past 15
years, compounding pharmacist George Muller
has prepared a transdermal gel containing
ketoprofen, lidocaine, clonidine, and gaba-
pentin that I apply topically once or twice
weekly to break my pain cycle, although that
compound can be applied as often as every 4
hours. I have never taken oral pain medications
other than anti-inammatory agents. Some of
those drugs, like rofecoxib, have been removed
from the U.S. market; others, like celecoxib, I
avoid because of their efects on the kidneys.
Opioids such as oxycodone (OxyContin) or
acetaminophen and hydrocodone (Vicodin),
which may efectively relieve acute pain, tend
to alter the opiate receptor and lower the pain
threshold. Because opioids are inefective in
relieving chronic pain, many patients treated
with those agents attempt to achieve relief by
increasing the dose. In doing so, they lower
their pain threshold (thus increasing their
sensitivity to pain) and risk addiction. For those
reasons, treatment with anti-inammatory
drugs and/or alternative methods, such as cold
laser therapy, is preferable. Topically applied
compounded gels are always worth trying, and
there is no commercially available equivalent to
those formulations. In my case, treatment with
the combination of the analgesic transdermal
gel compounded by George Muller, cold laser
treatment, ibuprofen, and rest provides about
3 days of pain relief (a reduction in pain and
swelling) or reduces my pain level by about
70%. To treat breakthrough pain, I apply the
gel, which is administered in a 1-mL syringe,
every 4 hours once or twice weekly to the
painful area. Applying the preparation after
having taken a hot shower enhances its efect. I
continue to use and prescribe that compound
because its efect is localized, the source of
the pain is treated directly, there is no risk of
addiction, and adverse systemic efects are pre-
vented. George Muller is an extremely creative
and knowledgeable compounder, and he is very
easy to work with. He is an excellent resource
for pain management, and my patients and I
continue to benet from his expertise.
Conclusion
Pain caused by disorders of movement,
which is often refractory to treatment with
Feature
commercially available analgesic agents, can
greatly compromise quality of life. Patients
who experience severe chronic
pain often benet from a
compounded medica-
tion that is cus-
tomized to meet
their specic
medical needs and
provides needed
relief without the
risk of addiction
or adverse systemic
afects. For those
individuals, the skill of
a compounding pharma-
cist who is knowledgeable
about the mechanisms of pain and appropriate
combinations of analgesic agents can be the
key to nding safe and efective treatment.
References
1. Department of Health and Human Ser-
vices. Centers for Disease Control and
Prevention. Chronic Disease Prevention
and Health Promotion. Arthritis. Meeting the
Challenge. At a Glance 2009. Atlanta, Geor-
gia: Centers for Disease Control and Pre-
vention 2008. [CDC Website.] Available
at: www.cdc.gov/nccdphp/publications/
aag/arthritis.htm. Accessed September 14,
2009.
Prevention. MMWR Morb Mortal Wkly Rep
2009; 58(16): 421. [CDC Website.] Avail-
able at: www.arthritis.org/media/mmwr-
disability-study-05-2009.pdf. Accessed
September 15, 2009.
Prevention. Chronic Disease Prevention and
Health Promotion. Quick stats on arthritis.
[CDC Website.] Available at: www.cdc.
gov/arthritis/pressroom/index.htm. Ac-
cessed September 16, 2009.
4. McNulty JP, Muller G. Update on manag-
ing neuropathic pain. IJPC 2009; 13(3):
182190.
5. National Institutes of Health. National
Institute of Neurological Diseases and
Stroke. [NIH Website.] Available at: www.
ninds.nih.gov/disorders/post_polio/de-
tail_post_polio.htm#107183172. Accessed
September 18, 2009.
6. McAlindon TE, Felson DT, Zhang Y et al.
Relation of dietary intake and serum levels

Compounded Analgesics Relieve Pain from Arthritis, Neuropathy, Postpolio Syndrome

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Compounded Analgesics Relieve Pain from Arthritis, Neuropathy, Postpolio Syndrome

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International Journal of Pharmaceutical Compounding

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