Feature

( VE TER INA RY )

Compounded Pimobendan
for Canine Chronic Degenerative Mitral
Valve Disease and Pulmonary Hypertension

Scott R. Helms, DVM, Diplomate ABVP

Samantha Fox, BA, CPhT
William Mixon, RPh, MS, FIACP
Jane Vail

L eft
P u lmonary
A rtery

M itral
Valve

The authors’ affiliations are as follows: Scott R. Helms, Veterinary Referral Hospital of Hickory, Hickory, North Carolina; Samantha Fox and
William Mixon, The Compounding Pharmacy, Hickory, North Carolina; Jane Vail, St. Louis, Missouri.

International Journal of Pharmaceutical Compounding www.ijpc.com

34 Vol. 16 No. 1 | January/February 2012

Abstract
Pimobendan (Vetmedin) is an effective treatment for
canine chronic degenerative mitral valve disease and
dilated cardiomyopathy. In an off-label use, it may also
be of benefit for the treatment of pulmonary hyperten-
sion in dogs. In this report, we describe the effects of
a palatable customized oral form of pimobendan used
with both compounded and commercially manufac-
tured conventional drug therapy to treat degenera-
tive mitral valve disease and pulmonary hypertension
in two small dogs. For those patients, who resisted
many types of oral medication, the standard manufac-
tured dose of pimobendan was inappropriate. Formu-
lations of the preparations used to treat the patients
described in this report are provided for easy refer-
ence. It should be noted that at the time of this writ-
ing, Boehringer Ingelheim GmbH (Ingelheim am Rhein,
Germany), the manufacturer of pimobendan, has
expressed concern about the stability of that agent in
aqueous compounded form. To our knowledge, no cur-
rent data confirming the stability or bioequivalence of
compounded pimobendan exist.
The phosphodiesterase 3 inhibitor (PDE3) pimobendan
(Vetmedin) has proven to be an effective treatment for chronic
degenerative mitral valvular disease1-2 and pulmonary hyperten-
sion caused by degenerative mitral valve disease in dogs.3 The
standard dose of manufactured capsules of pimobendan, which
can be obtained from the United Kingdom, is often too high for
use in small dogs. At the time of this writing, pimobendan that
is available in the U.S. for canine patients is dispensed only in
chewable tablets, which are scored but friable (especially when
the tablets are split into quarters for smaller patients). Attempt-
ing to divide pimobendan tablets into doses appropriate for small
dogs can result in inconsistent, inaccurate, or inadequate dosing.
Thus those patients may benefit from a compounded liquid form
of that agent. In addition, some dogs refuse oral manufactured
pimobendan, even when it is provided in a treat or favorite food,
but a more palatable (flavored) dosage form can improve com-
pliance with treatment. It should be noted, however, that at the
time of this writing, Boehringer Ingelheim GmbH (Ingelheim
am Rhein, Germany), the manufacturer of pimobendan, has con-
cerns about the stability of that drug in an aqueous compounded
form. To our knowledge, no current data that support the stabil-
ity or bioequivalence of compounded pimobendan exist.
In this article, we describe the effects of a compounded oral
flavored suspension of pimobendan in fixed oil that was used in
addition to compounded conventional and manufactured phar-
macotherapy to treat degenerative mitral valve disease and pul-
monary hypertension in two small dogs. Those patients could not
tolerate the standard dose of pimobendan and resisted treatment
with the manufactured tablet form of that drug.
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Feature
Pimobendan: Mechanism of
Action
Intracellular concentrations of cyclic adenosine monophos-
phate (cAMP), a cellular second messenger, have an import role
in the regulation of cardiac muscle contraction. Activation of the
sympathetic nervous system releases the neurotransmitter norepi-
nephrine and increases circulating catecholamines (epinephrine
and norepinephrine). Those catecholamines bind primarily to
beta1-adrenoceptors that are coupled to Gs proteins, an action that
results in cAMP production. cAMP is broken down by an enzyme
called cAMP-dependent phosphodiesterase, the inhibition of which
results in an increased level of cAMP and a subsequent increase in
cardiac inotropy, chronotropy, and dromotropy. Cyclic guanosine
monophosphate (cGMP) is another cellular second messenger that
is regulated by phosphodiesterase enzymes. Both cGMP and cAMP
have important roles in the relaxation of vascular smooth muscle.
Several subtypes of phosphodiesterase inhibitors, which improve
cardiac contractility and cause vascular dilation, have been identi-
fied. Pimobendan, amrinone, and milrinone are phosphodiesterase
3 inhibitors that exert positive inotropic effects on the heart and
positive vasodilatory effects in the systemic vasculature. Phospho-
diesterase 5 inhibitors (e.g., sildenafil), which are another important
phosphodiesterase-inhibitor subtype, increase the level of cGMP in
the corpus cavernosum of the penis and the vascular smooth muscle
of the pulmonary arteries. The action of phosphodiesterase 5 inhibi-
tors on the pulmonary arteries renders those drugs valuable phar-
macologic agents for the treatment of pulmonary hypertension. To
our knowledge, the only clinical application for sildenafil in animals
is the treatment of pulmonary hypertension.
Pimobendan, a PDE3, exhibits a dual mechanism of action in
increasing myocardial contractility: It increases calcium sensitivity
to troponin C in the myocardium, and it promotes systemic vaso-
dilation. The vasodilatory effects of that PDE3 inhibitor increase
organ perfusion by decreasing systemic vascular resistance. The
cardiopulmonary effects of phosphodiesterase inhibitors include an
increase in contractility, stroke volume, and ejection fraction.
Preload, the first determinant of cardiac contractility, is the mag-
nitude of the end-diastolic pressure that stretches the ventricles.
When cardiac output increases, preload decreases. Afterload, which
is the second determinant of cardiac contraction, is the force that
opposes muscle contraction. Afterload increases when intraven-
tricular pressure increases, but arterial dilation decreases afterload.
During systole, intraventricular pressure is usually the same as the
systolic systemic arterial blood pressure. The inotropic and vaso-
dilatory actions of the phosphodiesterase inhibitor pimobendan
decrease both preload and afterload, an effect that renders that drug
suitable for the treatment of heart failure.
PDE 3 inhibitors such as pimobendan may also have a role in
inhibiting platelet aggregation4 and in the regulation of hormones
associated with bone metabolism,5 follicle-stimulating hormone,6
lipolysis,7 and the effects of nitric oxide on renal vasculature.8
However, pimobendan is a fragile molecule that must be complexed
into a potassium citrate shell to ensure stability. The U.S. patent
information on oral pharmaceutical forms of pimobendan9 refers
to marked variability in the bioavailability of pimobendan that is
not complexed into a citrate shell. In the application for that patent,
International Journal of Pharmaceutical Compounding
Vol. 16 No. 1 | January/February 2012 35
Feature
Gruber and colleagues presented evidence that even complexed
pimobendan is rapidly disrupted in an aqueous environment.9 The
administration of pimobendan in an aqueous solution would likely
result in poor or no efficacy, and in other inappropriate prepara-
tions, pimobendan is significantly and rapidly degraded by oxida-
tion. However, to our knowledge, the long-term stability of pimo-
bendan in oil has not yet been evaluated. As with all compounded
preparations, the stability, potency, bioavailability, and clinical
efficacy of pimobendan should be established before the use of that
drug in customized formulations is accepted.
Rx Pimobendan 5-mg/mL Fixed-oil
Suspension
For 5 mL
Pimobendan (Vetmedin) 5-mg capsules 5 capsules
Silica gel 0.05 g
Flavor, grilled chicken, oil miscible
Almond oil qs
0.32
5
mL
mL
CAUTION: Only pimobendan (Vetmedin) in capsule form
(instead of chewable tablets) should be used in compounded for-
mulations of that drug. Pimobendan is a fragile molecule that
must be complexed into a potassium citrate shell to ensure stabil-
ity and bioavailability. That complex is rapidly disrupted in an
aqueous environment. Thus a compounded aqueous suspension
of pimobendan would provide poor or no efficacy due to the insta-
bility of the drug and the resultant lack of its bioavailability.9
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. Connect two Luer-Lok syringes (appropriate size) together with a Luer-
to-Luer connector after having removed the plunger from one syringe.
4. Add the flavor and 1 mL of almond oil to the open syringe.
5. Add the silica gel and the pimobendan from the capsules to the syringe.
6. Add 1 mL of almond oil to the syringe, replace the plunger, remove the air
from the syringe, and mix the contents.
7. Bring to volume with almond oil and mix well between the syringes.
PACKAGING
Package in white opaque polyethylene bottles with the appropriate measur-
ing devices.
LABELING
Shake well. No refrigeration needed.
STABILITY
A conservative beyond-use date of 90 days may be assigned to this
preparation.
USE
This preparation is used to alleviate the signs of heart failure in dogs by
increasing cardiac contractility and dilating blood vessels.
International Journal of Pharmaceutical Compounding
36 Vol. 16 No. 1 | January/February 2012
“....in dogs with congestive heart failure
caused by dilated cardiomyopathy or
chronic degenerative valvular disease,
pimobendan was safe and well tolerated.
Its use led to an enhanced quality of life
when it was administered in addition
to furosemide or another conventional
therapy such as an angiotensin-
converting enzyme inhibitor or digoxin.”
Pimobendan in Canine
Degenerative Mitral Valve Disease
The effectiveness of pimobendan in treating the effects of canine
degenerative mitral valve disease has been reported in the literature
and is well established. According to Atkins and colleagues, the
American College of Veterinary Internal Medicine recommends the
use of pimobendan to treat canine heart failure caused by chronic
degenerative mitral valve disease.1 In the prospective single-blinded
Quality of Life and Extension of Survival Time (QUEST) study,
Häggström and colleagues explored whether pimobendan, when
administered in addition to conventional therapy, would extend
time to sudden cardiac death, euthanasia for cardiac reasons, or
treatment failure when compared with benazepril plus conven-
tional therapy in dogs with congestive heart failure caused by
myxomatous mitral valve disease.2 In that study, 124 dogs with that
disorder were randomized to treatment with pimobendan plus con-
ventional therapy, and 128 received benazepril plus conventional
therapy. The primary endpoint was a composite of cardiac death,
euthanasia for heart failure, or treatment failure. One hundred
ninety dogs reached the primary endpoint, and the median time
was 188 days (267 days for the pimobendan group and 140 days for
the benazepril group; hazard ratio, 0.688; 95% confidence limits,
0.516 to 0.916; P = .0099). The benefit of pimobendan persisted after
adjustment for all baseline variables. A longer time to reach the
endpoint was also associated with the Cavalier King Charles spaniel
breed, a higher creatinine concentration, and requiring a lower furo-
semide dose. Increases in several indicators of cardiac enlargement
(the left atrial to aortic root ratio, the vertebral heart scale, a worse
tolerance for exercise, and the percentage of increase in the left ven-
tricular internal diameter in systole) were associated with a shorter
time to the endpoint.
In their review, Gordon and colleagues10 found that in dogs with
congestive heart failure caused by dilated cardiomyopathy or
chronic degenerative valvular disease, pimobendan was safe and
well tolerated. Its use led to an enhanced quality of life when it was
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administered in addition to furosemide or another conventional
therapy such as an angiotensin-converting enzyme (ACE) inhibitor
or digoxin. Those authors concluded that treatment with pimo-
bendan reduced mortality from canine congestive heart failure
associated with dilated cardiomyopathy. Fuentes and colleagues
also found that pimobendan produced favorable effects in dogs with
dilated cardiomyopathy.11 It must be noted, however, that pimoben-
dan should not be used as a monotherapy for heart failure. Instead,
it should be used with another drug therapy such as a diuretic agent
or an ACE inhibitor.
Pimobendan in Dogs with
Pulmonary Hypertension
Although at this time pimobendan is not thought to exert appre-
ciable phosphodiesterase 5 inhibition activity, it may be beneficial
in the treatment of canine pulmonary hypertension. In a study by
Atkinson and colleagues, pimobendan was shown to be of benefit in
the treatment of pulmonary hypertension caused by degenerative
mitral valve disease in dogs.3 The study results revealed that pimo-
bendan lowered the severity of measurable pulmonary hypertension,
improved quality-of-life scores, and decreased N-terminal probrain
natriuretic peptide concentrations and peak tricuspid regurgitant
flow velocity. The reduction in peak tricuspid regurgitant flow veloc-
ity persisted. However, at day 91 of the study, both pulmonary artery
acceleration and ejection times had increased significantly.
Studies in Progress
In research that is ongoing at the time of this writing, the effec-
tiveness of pimobendan is being evaluated in the treatment of
canine chronic degenerative mitral valve disease and dilated cardio-
myopathy before the onset of heart failure. The Evaluation of Pimo-
bendan in Dogs with Cardiomegaly Caused By Preclinical Mitral
Valve Disease (EPIC) study12 is assessing the effects of that drug in
dogs with chronic degenerative mitral valve disease. It has been our
experience that pimobendan, when administered with traditional
therapy, improves quality of life and extends survival in canine
patients with chronic degenerative mitral valve disease or dilated
cardiomyopathy and may also be of benefit in dogs with pulmonary
hypertension.
Compounded medications can often enable the safe and effective
treatment of dogs for which standard doses of manufactured drugs
are not appropriate. Smaller dogs frequently cannot tolerate the
standard dose of manufactured pimobendan, and for those patients,
a customized medication renders effective treatment possible. As
we stated previously, Boehringer Ingelheim GmbH (Ingelheim am
Rhein, Germany), the manufacturer of pimobendan, has concerns
that this drug is unstable in aqueous solutions. To our knowledge,
no current data that support the stability of compounded pimo-
bendan exist, and we could not clinically determine whether the
documented improvements in the health of the patients described
in this report were due to a response to a compounded oil suspen-
sion of pimobendan or to the conventional medication that they
also received. Studies determining the stability of compounded
pimobendan must be conducted, and due diligence regarding its
use in dogs must be performed. In the case reports presented in this
report, we describe the effects of pimobendan compounded in an
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Feature
oil suspension that was used in addition to other pharmacotherapy
to treat degenerative mitral valve disease and pulmonary hyperten-
sion in a Maltese dog and degenerative mitral valve disease in a
Chihuahua. We recommend that only pimobendan in capsule form
(as opposed to chewable tablets) be used in compounded formula-
tions of that drug.
Conclusion
The oral inodilator compound pimobendan, which is used in the
treatment of canine heart failure secondary to degenerative mitral
valve disease and dilated cardiomyopathy, exerts a dual effect in
increasing myocardial contractility; it increases calcium sensitivity
to troponin C in the myocardium, and it promotes systemic vaso-
dilation. The vasodilatory action of pimobendan increases organ
perfusion by decreasing systemic vascular resistance. In addition,
pimobendan appears to be effective in treating canine pulmonary
hypertension secondary to degenerative mitral valve disease. How-
ever, pimobendan is often prescribed with another agent (a diuretic
medication, an ACE inhibitor) used to treat canine heart failure.
Although the manufacturer of pimobendan has expressed con-
cern about the stability of that agent in compounded aqueous solu-
tions, the small dogs described in this report, whose size rendered
the standard doses of manufactured pimobendan inappropriate,
demonstrated benefit from treatment with compounded pimoben-
dan in a fixed-oil suspension that was administered in addition to
a standard drug regimen for degenerative mitral valve disease and
pulmonary hypertension.
References
1. Atkins C, Bonagura J, Ettinger S et al. Guidelines for the diagnosis
and treatment of canine chronic valvular heart disease. J Vet Intern
Med 2009; 23(6): 1142–1150.
2. Häggström J, Boswood A, O'Grady M et al. Effect of pimobendan
or benazepril hydrochloride on survival times in dogs with conges-
tive heart failure caused by naturally occurring myxomatous mitral
valve disease: The QUEST study. J Vet Intern Med 2008; 22(5):
1124–1135.
3. Atkinson KJ, Fine DM, Thombs LA et al. Evaluation of pimobendan
and N-terminal probrain natriuretic peptide in the treatment of
pulmonary hypertension secondary to degenerative mitral valve
disease in dogs. J Vet Intern Med 2009; 23(6): 1190–1196.
4. Shakur Y, Holst LS, Landstrom TR et al. Regulation and function of
the cyclic nucleotide phosphodiesterase (PDE3) gene family. Prog
Nucleic Acid Res Mol Biol 2001; 66: 241–277.
5. Ahlström M, Pekkinen M, Huttunen M et al. Cyclic nucleotide
phosphodiesterases (PDEs) in human osteoblastic cells; the effect
of PDE inhibition on cAMP accumulation. Cell Mol Biol Lett 2005;
10(2): 305–319.
6. Sasseville M, Albuz FK, Côté N et al. Characterization of novel
phosphodiesterases in the bovine ovarian follicle. Biol Reprod 2009;
81(2): 415–425.
7. Reinhardt RR, Chin E, Zhou J et al. Distinctive anatomical patterns
of gene expression for cGMP-inhibited cyclic nucleotide phospho-
diesterases. J Clin Invest 1995; 95(4):1528–1538. Erratum in: J Clin
Invest. 1997; 99(3): 551.
8. Sandner P, Kornfeld M, Ruan X et al. Nitric oxide/cAMP interac-
tions in the control of rat renal vascular resistance. Circ Res 1999;
84(2): 186–192.
International Journal of Pharmaceutical Compounding
Vol. 16 No. 1 | January/February 2012 37
Feature
9. Gruber P, Roth W, Schepky G, inventors; Dr. Karl Thomae, GmbH, assignee. Oral pharmaceu-
tical forms of pimobendan. US patent application 5,364, 646. November 25, 1994.
10. Gordon SG, Miller MW, Saunders AB. Pimobendan in heart failure therapy—a silver bullet? J
Am Anim Hosp Assoc 2006; 42(2): 90–93.
11. Fuentes VL, Corcoran B, French A et al. A double-blind, randomized, placebo-controlled
study of pimobendan in dogs with dilated cardiomyopathy. J Vet Intern Med 2002; 16(3):
255–261.
12. Boswood A, Smith S, Patteson M. Evaluation of pimobendan in dogs with cardiomegaly
caused by preclinical mitral valve disease. Vet Rec 2011; 168(8): 222.
Case Reports
Case 1
In early March 2010, an 11-year-old
spayed female Maltese dog was referred to
the Veterinary Referral Hospital of Hick-
ory in Hickory, North Carolina, after hav-
ing exhibited persistent lethargy and inap-
petence as well as repeated bouts of cough-
ing. Physical examination, radiographic
studies, a cardiac evaluation, and the
results of blood chemistry analyses yielded
a diagnosis of cardiomegaly, degenerative
mitral valve disease, and severe pulmonary
hypertension. The results of the patient’s
laboratory analyses were within limits
with the exception of mild leukocytosis.
The patient was admitted to the Veterinary
Referral Hospital for overnight oxygen
therapy, which improved her ability to
breathe. Sildenafil (Viagra) is often used
off label to treat pulmonary hypertension
in dogs. However, the manufactured form
of sildenafil is available only in a dose too
high for this patient. This dog was dis-
charged to home the next day with a pre-
scription for a flavored compounded oral
International Journal of Pharmaceutical Compounding
38 Vol. 16 No. 1 | January/February 2012
aqueous suspen-
sion of sildenafil
(2 mg every 12
hours for 30 days
with 1 refill) and
ten 2.5-mg manu-
factured tablets
of enalapril (one-
half tablet to be
administered each
morning and one-
half tablet each
evening until gone).
At-home oxygen
therapy was recom-
mended, but the
owner declined.
The dog’s prognosis
was stated to be guarded to poor.
Approximately 1 week later, this patient
was reexamined, and at that time the owner
reported that the dog’s food and water
intake and overall condition had improved
at home (no further bouts of coughing
had occurred). The heart murmur was
unchanged, and no pulmonary edema was
detected. To ensure compliance and correct
dosing, a compounded oral-flavored aque-
ous suspension of enalapril (1.25 mg every
12 hours for 60 days) was prescribed with
1 refill, and treatment with the previously
prescribed compounded oral suspension of
sildenafil (2 mg every 12 hours for 60 days)
was continued.
Approximately 1 month later, this dog
was reexamined. She had exhibited mini-
mal coughing at home, and her food and
water intake (as well as her activity level)
were reported to be normal. Radiographs
revealed that her marked cardiomegaly was
unchanged from that noted in prior imag-
ing, and no pulmonary edema was found.
The patient exhibited significant exertional
cyanosis but did well when she was not
exerting herself. No changes in therapy
were recommended.
Recommended
Reading
• Atkinson KJ, Fine DM, Thombs LA et al.
Evaluation of pimobendan and N-termi-
nal probrain natriuretic peptide in the
treatment of pulmonary hypertension
secondary to degenerative mitral valve
disease in dogs. J Vet Intern Med 2009;
23(6): 1190–1196.
• Boswood A. Current use of pimobendan
in canine patients with heart disease. Vet
Clin North Am Small Anim Pract 2010;
40(4): 571–580.
• Boswood A, Smith S, Patteson M. Evalu-
ation of pimobendan in dogs with car-
diomegaly caused by preclinical mitral
valve disease. Vet Rec 2011; 168(8): 222.
• Chetboul V, Lefebvre HP, Sampedrano
CC et al. Comparative adverse cardiac
effects of pimobendan and benazepril
monotherapy in dogs with mild degen-
erative mitral valve disease: A prospec-
tive, controlled, blinded, and randomized
study. J Vet Intern Med 2007; 21(4):
742–753.
• Grady MR, Minors SL, O'Sullivan ML et
al. Effect of pimobendan on case fatality
rate in doberman pinschers with con-
gestive heart failure caused by dilated
cardiomyopathy. J Vet Intern Med 2008;
22(4): 897–904.
• Häggström J, Boswood A, O'Grady M et
al. Effect of pimobendan or benazepril
hydrochloride on survival times in dogs
with congestive heart failure caused by
naturally occurring myxomatous mitral
valve disease: The QUEST study. J Vet
Intern Med 2008; 22(5): 1124–1135.
• Martin MW, Stafford Johnson MJ,
Strehlau G et al. Canine dilated cardio-
myopathy: A retrospective study of prog-
nostic findings in 367 clinical cases. J
Small Anim Pract 2010; 51(8): 428–436.
• Ouellet M, Bélanger MC, Difruscia R et
al. Effect of pimobendan on echocardio-
graphic values in dogs with asymptom-
atic mitral valve disease. J Vet Intern
Med 2009; 23(2): 258–263.
For additional information, contact Jane
Vail at janevail@sbcglobal.net.
www.ijpc.com
 Feature

During the first week of July, this patient was reexamined. She
had been feeling well at home and her food and water intake were
normal, but her breathing was labored. Palpable hepatomegaly
was noted, and mild azotemia was identified. No changes in phar-
macotherapy were recommended.
At a follow-up examination in early October, the patient’s
owner reported that this dog had been feeling relatively well at
home and was eating normally but that her breathing remained
labored and she was less active. Radiographs revealed that the
cardiac silhouette and the caudal lobar pulmonary arteries had
enlarged, and the patient was found to have deteriorated clini-
cally. Recommended treatment consisted of continuing the
administration of the compounded formulations of enalapril and
sildenafil as previously prescribed and adding a compounded
flavored fixed-oil suspension of pimobendan (0.5 mg every 12
hours for 30 days with 1 refill) to that regimen. At-home oxygen
therapy was again recommended, but the owner again declined
that treatment. An examination approximately 10 days later
revealed that the patient’s overall condition had improved since
compounded pimobendan was added to her treatment regimen.
She was eating and drinking normally, although she had been
coughing and her breathing was labored. No changes to her cur-
rent therapy were recommended.
In February 2011, the patient was reexamined. She had been
feeling well at home, although she exhibited a nonproductive
cough after drinking. Her labored breathing persisted but had
not worsened since her last visit. The nonproductive cough was
likely due to underlying lung pathology, to marked cardiomegaly

Rx
and displacement of the trachea, or (less likely) to sensory
dysfunction in the pharyngeal area. No changes to therapy
Enalapril 1.25-mg/mL Suspension
were recommended.

For 60 mL

Enalapril maleate
Glycerin
Flavor, chicken slurry vehicle
0.075
2
30
g
mL
mL
Rx Sildenafil Citrate 4 mg/mL

For 100 mL
Suspension vehicle w/xanthan gum qs 60 mL

Sildenafil citrate (100-mg Viagra tablets) 4 Tablets

Note: Chicken slurry vehicle, which contains one 10-ounce can of
canned chicken, 1 packet of Herb-Ox (Hormel Foods Corporation,
Austin, Minnesota) sodium-free chicken bouillon, and 600 mL of a
suspension vehicle with xanthan gum, must be stored frozen until
needed.
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. Triturate the enalapril in a mortar with the glycerin to make a smooth
paste.
4. Add the flavor and mix well.
5. Check the pH of the formulation. Adjust the pH to 3 to 5 by using citric acid
10% W/V/water. Note: Check the pH after each addition.
6. Bring to volume with the suspension vehicle and recheck the pH.
PACKAGING
Package in white opaque polyethylene bottles with the appropriate measuring
devices.
LABELING
Shake well. Refrigerate and protect from light.
Bitter drug base 2.6 g
Flavor, beef, water miscible 3 mL
Water, purified 5 mL
Suspension vehicle with xanthan gum qs 100 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. Reduce the sildenafil citrate (Viagra) tablets to a fine powder. Note: The
coating on the Viagra tablets can be removed before comminution by wiping
the tablets with a 50:50 mixture of alcohol and acetone.
4. Add the bitter drug base and triturate until the mixture is uniform.
5. Add the distilled water.
6. Triturate the mixture until a smooth creamy paste results.
7. Add the flavor and the suspension vehicle by using geometric dilution until
the mixture is pourable.
8. Bring to final volume with the suspension vehicle with xantham gum.
PACKAGING
Package in white opaque polyethylene bottles with the appropriate measuring
devices.

STABILITY LABELING
A conservative beyond-use date of 45 days may be assigned to this prepara- Shake well. Store at room temperature.
tion.
STABILITY
STORAGE A conservative beyond-use date of 90 days may be assigned to this prepara-
Refrigerate. tion.

USE USE
This preparation is used for the treatment of heart failure, hypertension, and This preparation is used for the treatment of pulmonary hypertension in
chronic renal failure in dogs. animals.

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Vol. 16 No. 1 | January/February 2012 39
Feature
In early April, this dog became acutely paraplegic, but that state
resolved on the same day. Later that day, however, painful para-
paresis and diarrhea developed without evidence of spinal hyper-
esthesia. Because this patient was clearly uncomfortable and her
clinical condition was worsening, the owner requested that her dog
be euthanized.
This small dog could not tolerate the doses of enalapril, sildenafil,
and pimobendan that are commercially available, but compound-
ing those drugs into a palatable form of the correct dose produced a
temporary clinical improvement in her disease and prolonged her
quality of life. The addition of compounded pimobendan to a stan-
dard treatment regimen proved especially helpful in relieving her
symptoms of pulmonary hypertension and cardiac disease.
Case 2
In late November 2010, an 11-year-old spayed female Chihuahua
was referred to the Veterinary Referral Hospital of Hickory in
Hickory, North Carolina, for the treatment of renal insufficiency
and repeated episodes of weakness and collapse. The weakness
persisted for only a few minutes, and this patient appeared normal
soon after each episode. Shortly before her visit to the Veteri-
nary Referral Hospital, she had also begun to exhibit episodes of
labored breathing as well as inappetence and decreased water
intake. The results of physical examination, chest radiographs, an
echocardiogram, and blood chemistry analyses performed at the
Referral Hospital revealed advanced myxomatous degeneration
of the mitral valve, marked mitral valve regurgitation, pulmonary
edema, and mild azotemia. The bouts of weakness were thought to
result from vasovagal episodes.
Pimobendan and furosemide are established pharmacotherapy
for heart failure secondary to chronic degenerative mitral valve
disease in dogs. Initially, this patient was treated with commer-
cially available pimobendan, but a compounded medication was
considered because compliance became a problem. Treatment
with a 10-day course of a compounded flavored oral fixed-oil
suspension of pimobendan (5 mg/mL, 1.25 mg [0.25 mL] every
12 hours) and a compounded flavored aqueous suspension of
furosemide (25 mg/mL, 6.25 mg [0.25 mL] every 12 hours) was
then initiated.
At a follow-up examination 1 week later, the patient was feeling
well. She had experienced no additional syncopal episodes. Tho-
racic imaging revealed a marked radiographic improvement and
resolution of the pulmonary edema. No changes in the prescribed
therapeutic regimen were made. In February 2011, however, this
dog began to refuse food and water and again experienced dif-
ficulty in breathing. She was admitted to the Veterinary Referral
Hospital emergency service for treatment, at which time she was
dyspneic and her respiratory rate was elevated. Thoracic aus-
cultation revealed bilateral crackles. The character of the heart
murmur was unchanged. Thoracic radiographs showed pulmonary
edema. Oxygen and intravenous furosemide were administered,
and the patient’s respiratory rate and dyspnea decreased. She was
discharged to home with the recommendation to continue treat-
ment as previously prescribed with compounded pimobendan and
furosemide in addition to an oral appetite stimulant (mirtazapine,
International Journal of Pharmaceutical Compounding
40 Vol. 16 No. 1 | January/February 2012
1.875 mg [one-eighth of a 15-mg commercially manufactured tab-
let] once daily as needed).
A radiographic reexamination performed in March 2011 showed
that the patient’s heart had significantly enlarged. Both hypo-
kalemia and azotemia were noted, but there was no pulmonary
edema. This dog had been feeling well at home, despite occasional
bouts of coughing. She had been receiving pimobendan in a fixed-
oil suspension, but because of concerns about the stability of
compounded pimobendan in aqueous suspensions that had been
expressed by the manufacturer of that drug (and the lack of studies
confirming or refuting the stability of compounded pimobendan),
commercially available pimobendan was again prescribed at a dos-
age of one 1.25-mg tablet in the morning and one 1.25-mg tablet
in the evening instead of the compounded form. Treatment with
a commercially available oral potassium gluconate supplement
(1 mEq every 12 hours) was also prescribed.
On reexamination 2 weeks later, the patient exhibited somewhat
labored breathing, increasing hypokalemia, and a very elevated
heart rate. No pulmonary edema was identified on thoracic
Rx
Furosemide 25-mg/mL Suspension
For 60 mL
Furosemide 1.5 g
Glycerin 2 mL
Flavor, chicken slurry vehicle qs 60 mL
Note: Chicken slurry vehicle, which contains one 10-ounce can of canned
chicken, 1 packet of Herb-Ox (Hormel Foods Corporation) sodium-free chicken
bouillon, and 600 mL of a suspension vehicle with xanthan gum, should be
stored frozen until needed.
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. Triturate the furosemide in a mortar with the glycerin to make a smooth
paste.
4. Add the flavoring and mix well.
5. Check the pH. Adjust the pH to 8 to 9.5 by using a hydrochloric acid 10%
W/V/water solution or a sodium hydroxide 20% solution. Note: Check the
pH after each addition.
6. Bring to volume with the flavored chicken slurry vehicle and recheck the pH.
PACKAGING
Package in white opaque polyethylene bottle with the appropriate measuring
devices.
LABELING
Shake well. Refrigerate. Protect from light.
STABILITY
A conservative 45-day beyond-use date may be assigned to this preparation.
USE
This preparation is used as a loop diuretic.
www.ijpc.com

radiographs. Her azotemia had slightly
worsened. Her dose of compounded furo-
semide was reduced to 5 mg orally every
12 hours (0.2 mL of a 25-mg/mL suspen-
sion), and her dose of potassium gluconate
was increased to 2 mEq every 12 hours.
One week later, the owner stated that the
patient had been more active at home and
had not experienced additional episodes of
labored breathing. Treatment was contin-
ued as prescribed.
At a follow-up examination 1 week later,
the owner reported that the dog was feel-
ing well at home most days, despite occa-
sional vomiting; that she was more active;
and that she was eating and drinking well.
At that time, the dog’s heart rate was 148
beats per minute, and her respiratory rate
was 28 breaths per minute. Her potas-
sium level was within the normal range,
and her femoral pulses were strong and
synchronous. The heart murmur was
unchanged. Treatment was to be contin-
ued as last prescribed.
It should be remembered that this
patient was initially treated with com-
mercially available pimobendan, but when
compliance became an issue her treatment
www.ijpc.com
Feature
was changed to a compounded form of that
drug. When her condition deteriorated
clinically during therapy with the com-
pounded drug, her treatment was changed
back to commercially available pimoben-
dan because of concerns about whether
pimobendan would be stable even in a
fixed-oil preparation. However, no signifi-
cant further clinical improvement was
noted after the patient’s treatment had
been changed back to commercially avail-
able pimobendan. Although this dog died
at home in mid-April 2011, treatment with
customized medications improved compli-
ance, ensured that accurate doses were
administered, and temporarily prolonged
both the quality of her life and her survival.
International Journal of Pharmaceutical Compounding
Vol. 16 No. 1 | January/February 2012 41