scored and the calculated dosage should beprovided to the nearest half tablet increment.
Vetmedin should not be given
in cases of hypertrophic cardiomyopathy, aorticstenosis, or any other clinical condition where an
Federal law restricts this drug to use by
augmentation of cardiac output is inappropriate
or on the order of a licensed veterinarian.
for functional or anatomical reasons.
Vetmedin (pimobendan) is supplied as
Only for use in dogs with clinical
oblong half-scored chewable tablets containing
evidence of heart failure. At 3 and 5 times the
1.25 or 5 mg pimobendan per tablet. Pimobendan,
a benzimidazole-pyridazinone derivative, is a non-
6-month period of time, pimobendan caused
sympathomimetic, non-glycoside inotropic drug
an exaggerated hemodynamic response in the
with vasodilatative properties. Pimobendan exerts
normal dog heart, which was associated with
a stimulatory myocardial effect by a dual mechanism
cardiac pathology (See Animal Safety
of action consisting of an increase in calcium
Not for use in humans. Keep
sensitivity of cardiac myofilaments and inhibition
this and all medications out of reach of children.
of phosphodiesterase (Type III). Pimobendan exhibits
Consult a physician in case of accidental ingestion
vasodilating activity by inhibiting phosphodiesterase
III activity. The chemical name of pimobendan is 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-
The safety of Vetmedin has not been
established in dogs with asymptomatic heartdisease or in heart failure caused by etiologies
other than AVVI or DCM. The safe use of Vetmedinhas not been evaluated in dogs younger than6 months of age, dogs with congenital heartdefects, dogs with diabetes mellitus or otherserious metabolic diseases, dogs used forbreeding, or pregnant or lactating bitches.
Vetmedin (pimobendan) is indicated
reactions were recorded in a 56-day field study
of dogs with congestive heart failure (CHF) due
moderate, or severe (modified NYHA Class IIa,
to AVVI (256 dogs) or DCM (99 dogs). Dogs were
IIIb, or IVc) congestive heart failure in dogs due
treated with either Vetmedin (175 dogs) or the
to atrioventricular valvular insufficiency (AVVI)
active control enalapril maleate (180 dogs). Dogs
or dilated cardiomyopathy (DCM). Vetmedin is
in both treatment groups received additional
indicated for use with concurrent therapy for
background cardiac therapy (See Effectiveness
congestive heart failure (e.g., furosemide, etc.)
for details and the difference in digoxin
as appropriate on a case-by-case basis.
administration between treatment groups).
a A dog with modified New York Heart Association
The Vetmedin group had the following prevalence
(NYHA) Class II heart failure has fatigue, shortness
(percent of dogs with at least one occurrence)
of breath, coughing, etc. apparent when ordinary
of common adverse reactions/new clinical findings
(not present in a dog prior to beginning studytreatments): poor appetite (38%), lethargy (33%),
b A dog with modified NYHA Class III heart failure is
diarrhea (30%), dyspnea (29%), azotemia (14%),
comfortable at rest, but exercise capacity is minimal.
weakness and ataxia (13%), pleural effusion (10%),
c A dog with modified NYHA Class IV heart failure
syncope (9%), cough (7%), sudden death (6%),
has no capacity for exercise and disabling clinical
ascites (6%), and heart murmur (3%). Prevalence was
similar in the active control group. The prevalenceof renal failure was higher in the active control group
Dosage and Administration:
(4%) compared to the Vetmedin group (1%).
be administered orally at a total daily dose of0.23 mg/lb (0.5 mg/kg) body weight, using a
Adverse reactions/new clinical findings were seen in
suitable combination of whole or half tablets. The
both treatment groups and were potentially related
total daily dose should be divided into 2 portions
to CHF, the therapy of CHF, or both. The following
that are not necessarily equal, and the portions
adverse reactions/new clinical findings are listed
should be administered approximately 12 hours
according to body system and are not in order
apart (i.e., morning and evening). The tablets are
of prevalence: CHF death, sudden death, chordae
tendineae rupture, left atrial tear, arrhythmias
Pimobendan is oxidatively
overall, tachycardia, syncope, weak pulses, irregular
demethylated to a pharmacologically active
pulses, increased pulmonary edema, dyspnea,
metabolite which is then conjugated with sulfate
increased respiratory rate, coughing, gagging,
or glucuronic acid and excreted mainly via feces.
pleural effusion, ascites, hepatic congestion,
The mean extent of protein binding of pimobendan
decreased appetite, vomiting, diarrhea, melena,
and the active metabolite in dog plasma is >90%.
weight loss, lethargy, depression, weakness,
Following a single oral administration of 0.25 mg/kg
collapse, shaking, trembling, ataxia, seizures,
Vetmedin tablets the maximal mean (± 1 SD) plasma
restlessness, agitation, pruritus, increased water
concentrations (Cmax) of pimobendan and the
consumption, increased urination, urinary
active metabolite were 3.09 (0.76) ng/ml and
accidents, azotemia, dehydration, abnormal serum
3.66 (1.21) ng/ml, respectively. Individual dog Cmax
electrolyte, protein, and glucose values, mild
values for pimobendan and the active metabolite
increases in serum hepatic enzyme levels, and mildly
were observed 1 to 4 hours post-dose (mean: 2
and 3 hours, respectively). The total body clearanceof pimobendan was approximately 90 mL/min/kg,
See Table 1 for mortality due to CHF (including
and the terminal elimination half-lives of pimobendan
euthanasia, natural death, and sudden death) and
and the active metabolite were approximately
for the development of new arrhythmias (not
0.5 hours and 2 hours, respectively. Plasma levels
present in a dog prior to beginning study
of pimobendan and active metabolite were below
treatments) by treatment group and type of heart
quantifiable levels by 4 and 8 hours after oral
disease (AVVI or DCM) in the 56-day field study.
administration, respectively. The steady-state
Table 1: CHF Death and New Arrhythmias
volume of distribution of pimobendan is 2.6 L/kg,
in the 56-Day Field Study
indicating that the drug is readily distributed intotissues. Food decreased the bioavailability of an
Active Control Group
aqueous solution of pimobendan, but the effect
of food on the absorption of pimobendan from
In normal dogs instrumented with left ventricular
(LV) pressure transducers, pimobendan increased
LV dP/dtmax (a measure of contractility of the
heart) in a dose-dependent manner between 0.1 and
0.5 mg/kg orally. The effect was still present 8 hours
after dosing. There was a delay between peak bloodlevels of pimobendan and active metabolite and the
a New arrhythmias included supraventricular premature beats
maximum physiologic response (peak LV dP/dtmax).
and tachycardia, atrial fibrillation, atrioventricular block, sinus
Blood levels of pimobendan and active metabolite
bradycardia, ventricular premature beats and tachycardia,
began to drop before maximum contractility was
seen. Repeated oral administration of pimobendan
Following the 56-day masked field study, 137 dogs
did not result in evidence of tachyphylaxis
in the Vetmedin group were allowed to continue
(decreased positive inotropic effect) or drug
on Vetmedin in an open-label extended-use study
accumulation (increased positive inotropic effect).
without restrictions on concurrent therapy. The
Laboratory studies indicate that the positive
adverse reactions/new clinical findings in the
inotropic effect of pimobendan may be attenuated
extended-use study were consistent with those
by the concurrent use of a ß-adrenergic blocker
reported in the 56-day study, with the following
exception: One dog in the extended-use study
In a double-masked, multi-site,
developed acute cholestatic liver failure after
56-day field study, 355 dogs with modified NYHA
140 days on Vetmedin and furosemide.
Class II, III, or IV CHF due to AVVI or DCM wererandomly assigned to either the active control
In foreign post-approval drug experience reporting,
(enalapril maleate) or the Vetmedin (pimobendan)
the following additional suspected adverse reactions
treatment group. Of the 355 dogs, 52% were male
were reported in dogs treated with a capsule
and 48% were female; 72% were diagnosed with
formulation of pimobendan: hemorrhage, petechia,
AVVI and 28% were diagnosed with DCM; 34% had
anemia, hyperactivity, excited behavior, erythema,
Class II, 47% had Class III, and 19% had Class IV
rash, drooling, constipation, and diabetes mellitus.
CHF. Dogs ranged in age and weight from 1 to
To report suspected adverse reactions, to obtain
17 years and 3.3 to 191 lb, respectively. The most
a Material Safety Data Sheet, or for technical
Pinscher, Cocker Spaniel, Miniature/Toy Poodle,
At the end of the 56-day study, dogs in the Vetmedin
Maltese, Chihuahua, Miniature Schnauzer, Dachshund,
group were enrolled in an unmasked field study
and Cavalier King Charles Spaniel. The 180 dogs
to monitor safety under extended use, without
(130 AVVI, 50 DCM) in the active control group
restrictions on concurrent medications.
received enalapril maleate (0.5 mg/kg once or
Vetmedin was used safely in dogs concurrently
twice daily), and all but 2 received furosemide.
receiving furosemide, digoxin, enalapril, atenolol,
Per protocol, all dogs with DCM in the active
spironolactone, nitroglycerin, hydralazine, diltiazem,
control group received digoxin. The 175 dogs
antiparasitic products (including heartworm
prevention), antibiotics (metronidazole, cephalexin,
received pimobendan (0.5 mg/kg/day divided
amoxicillin-clavulanate, fluoroquinolones), topical
into 2 portions that were not necessarily equal,
ophthalmic and otic products, famotidine, theophylline,
and the portions were administered approximately
levothyroxine sodium, diphenhydramine, hydrocodone,
12 hours apart), and all but 4 received furosemide.
metoclopramide, and butorphanol, and in dogs on
Digoxin was optional for treating supraventricular
tachyarrhythmia in either treatment group, as wasthe addition of a ß-adrenergic blocker if digoxin
In a laboratory study, the palatability
was ineffective in controlling heart rate. After initial
of Vetmedin was evaluated in 20 adult female
treatment at the clinic on Day 1, dog owners were
Beagle dogs offered doses twice daily for 14 days.
to administer the assigned product and concurrent
Ninety percent (18 of 20 dogs) voluntarily consumed
more than 70% of the 28 tablets offered. Includingtwo dogs that consumed only 4 and 7% of the
The determination of effectiveness (treatment
tablets offered, the average voluntary consumption
success) for each case was based on improvement
in at least 2 of the 3 following primary variables:modified NYHA classification, pulmonary edema
In a laboratory study, Vetmedin
score by a masked veterinary radiologist, and the
chewable tablets were administered to 6 healthy
investigator’s overall clinical effectiveness score
Beagles per treatment group at 0 (control), 1, 3,
(based on physical examination, radiography,
and 5 times the recommended dosage for 6 months.
electrocardiography, and clinical pathology).
See Table 3 for cardiac pathology results. The cardiac
Attitude, pleural effusion, coughing, activity level,
pathology/histopathology noted in the 3X and 5X
furosemide dosage change, cardiac size, body
dose groups is typical of positive inotropic and
weight, survival, and owner observations were
vasodilator drug toxicity in normal dog hearts,
secondary evaluations contributing information
and is associated with exaggerated hemodynamic
supportive to product effectiveness and safety.
responses to these drugs. None of the dogs developed
Based on protocol compliance and individual
signs of heart failure and there was no mortality.
case integrity, 265 cases (134 Vetmedin, 131 active
Table 3: Incidence of Cardiac Pathology/
control) were evaluated for treatment success
Histopathology in the Six-month Safety Study
on Day 29. See Table 2 for effectiveness results.
Table 2: Effectiveness Results for the 56-Day
Severe left ventricular hypertrophy with
One 3X and
multifocal subendocardial ischemic lesions
two 5X dogsa
Moderate to marked myxomatous
Three 5X dogs
Active Control Group
thickening of the mitral valves
Myxomatous thickening of the
One 3X and
two 5X dogs
Endocardial thickening of the left
One 1X, two 3X,
ventricular outflow tract
and two 5X dogs
Left atrial endocardial thickening (jet
One 3X and
lesions) in 2 of the dogs that developed
one 5X dog
murmurs of mitral valve insufficiency
Granulomatous inflammatory lesion in the
One 3X dog
right atrial myocardium
a Most of the gross and histopathologic findings occurred in these
Murmurs of mitral valve insufficiency were
detected in one 3X (Day 65) and two 5X dogs
(Days 135 and 163). These murmurs (grades II-III
of VI) were not associated with clinical signs.
Indirect blood pressure was unaffected by
Boehringer Ingelheim Vetmedica, Inc.
Vetmedin at the label dose (1X). Mean diastolic
blood pressure was decreased in the 3X group
(82 mmHg). Mean systolic blood pressure was
decreased in the 5X group (117 mmHg) compared
licensed to Boehringer Ingelheim Vetmedica, Inc.
to the control group (124 mmHg). None of thedogs had clinical signs of hypotension.
2008 Boehringer Ingelheim Vetmedica, Inc.
On 24-hour Holter monitoring, mean heart rate
was increased in the 5X group (101 beats/min)
compared to the control group (94 beats/min).
Not counting escape beats, the 3X and 5X groupshad slightly higher numbers of isolated ventricularectopic complexes (VEs). The maximum numberof non-escape VEs recorded either at baselineor in a control group dog was 4 VEs/24 hours.
At either Week 4 or Week 20, three 3X group dogshad maximums of 33, 13, and 10 VEs/24 hours,and two 5X group dogs had maximums of 22 and9 VEs/24 hours. One 1X group dog with no VEs atbaseline had 6 VEs/24 hours at Week 4 and againat Week 20. Second-degree atrioventricular heartblock was recorded in one 3X group dog at Weeks4 and 20, and in one dog from each of the 1Xand 5X groups at Week 20. None of the dogshad clinical signs associated with theseelectrocardiogram changes.
Treatment was associated with small differencesin mean platelet counts (decreased in the 3X and1X groups), potassium (increased in the 5X group),glucose (decreased in the 1X and 3X groups),and maximum blood glucose in glucose curves(increased in the 5X group). All individual valuesfor these variables were within the normal range.
Three 1X and one 5X group dogs had mild elevationsof alkaline phosphatase (less than two timesnormal). Loose stools and vomiting wereinfrequent and self-limiting.
Store at controlled room
temperature 59-86°F (15-30°C).
Vetmedin® (pimobendan) Chewable Tablets:
Available as 1.25 or 5 mg oblong half-scored
chewable tablets — 50 tablets per bottle.
Beximco Pharmaceuticals Ltd. ( Beximco Pharma) belongs to Beximco Group, the largest privat va e sector industr ial conglomerat e in Bangladesh. The company is a leading man uf u act urer of pharmaceut icals - bot h finished formulat ions and Act ive Pharmaceut ical I ngredient s ( APIs). The st at e-of-t he-art man uf u act uring facilit ili ies of t he comp
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