Antiemetic
(maropitant citrate)
CERENIA (maropitant citrate) Injectable Solution
is indicated for the prevention and treatment of acute vomiting in dogs.
DOSAGE AND ADMINISTRATION: Administer
CERENIA Injectable Solution subcutaneously at 1.0 mg/kg (0.45 mg/lb)
equal to 1.0 mL/10 kg (1.0 mL/22 lb) of body weight once daily for up to
5 consecutive days.
For subcutaneous injection in dogs only
CERENIA Injectable Solution is recommended for
use in dogs 16 weeks and older.
|
Dog body weight
|
Dose Volume (mL)
|
|
Pounds
|
Kilograms
|
|
2.2
|
1.0
|
0.10
|
|
2.3 - 4.4
|
1.1 - 2.0
|
0.20
|
|
4.5 - 6.6
|
2.1 - 3.0
|
0.30
|
|
6.7 - 8.8
|
3.1 - 4.0
|
0.40
|
|
8.9 - 11.0
|
4.1 - 5.0
|
0.50
|
|
11.1 - 16.5
|
5.1 - 7.5
|
0.75
|
|
16.6 - 22.0
|
7.6 - 10.0
|
1.00
|
|
22.1 - 33.0
|
10.1 - 15.0
|
1.50
|
|
33.1 - 44.0
|
15.1 - 20.0
|
2.00
|
|
44.1 - 66.0
|
20.1 - 30.0
|
3.00
|
|
66.1 - 88.0
|
30.1 - 40.0
|
4.00
|
|
88.1 - 110.0
|
40.1 - 50.0
|
5.00
|
|
110.1 - 132.0
|
50.1 - 60.0
|
6.00
|
CERENIA Injectable Solution may be used
interchangeably with CERENIA Tablets for once daily dosing for the
prevention of acute vomiting.
WARNINGS: Not for use in humans. Keep out
of reach of children. In case of accidental injection or exposure, seek
medical advice. Topical exposure may elicit localized allergic skin
reactions in some individuals. Repeated or prolonged exposure may lead
to skin sensitization. In case of accidental skin exposure, wash with
soap and water. CERENIA is also an ocular irritant. In case of
accidental eye exposure, flush with water for 15 minutes and seek
medical attention.
In puppies younger than 11 weeks of age,
histological evidence of bone marrow hypoplasia was seen at higher
frequency and greater severity in puppies treated with CERENIA than in
control puppies. In puppies 16 weeks and older, bone marrow hypoplasia
was not seen (See Animal Safety Section).
PRECAUTIONS: For subcutaneous injection
only. The safe use of CERENIA has not been evaluated in dogs used for
breeding, pregnant or lactating bitches, dogs with gastrointestinal
obstruction, or dogs that have ingested toxins. Use with caution in dogs
with hepatic dysfunction. Use with caution with other medications that
are highly protein bound. The concomitant use of CERENIA with other
protein bound drugs has not been studied in dogs. Commonly used protein
bound drugs include NSAIDs, cardiac, anticonvulsant and behavioral
medications. The influence of concomitant drugs that may inhibit
metabolism of CERENIA has not been evaluated. Drug compatibility should
be monitored in patients requiring adjunctive therapy.
ADVERSE REACTIONS: In a US field study
for the prevention and treatment of vomiting associated with
administration of cisplatin for cancer chemotherapy, the following
adverse reactions were reported in 77 dogs treated with CERENIA
Injectable Solution at 1.0 mg/kg subcutaneously or 41 dogs treated with
placebo:
Frequency of Adverse Reactions by Treatment
|
Adverse Reaction
|
Placebo (n=41)
|
CERENIA (n=77)
|
|
# dogs
|
% occur
|
# dogs
|
% occur
|
|
Diarrhea
|
1
|
2.4
|
6
|
7.8
|
|
Anorexia
|
0
|
0
|
4
|
5.2
|
|
Injection site reaction (swelling, pain upon injection)
|
0
|
0
|
3
|
4.0
|
|
Lethargy
|
1
|
2.4
|
2
|
2.6
|
The following adverse reactions were reported
during the course of a US field study for the prevention and treatment
of acute vomiting in dogs treated with 1.0 mg/kg CERENIA Injectable
Solution subcutaneously and/or CERENIA Tablets at a minimum of 2 mg/kg
orally once daily for up to 5 consecutive days:
Frequency of Adverse
Reactions by Treatment
|
Adverse Reaction
|
Placebo (n=69)
|
CERENIA (n=206)
|
|
# dogs
|
% occur
|
# dogs
|
% occur
|
|
Death during study
|
4
|
5.8
|
10
|
4.9
|
|
Euthanized during study
|
0
|
0
|
2
|
1.0
|
|
Diarrhea
|
6
|
8.7
|
8
|
3.9
|
|
Hematochezia/bloody stool
|
5
|
7.2
|
4
|
1.9
|
|
Anorexia
|
2
|
2.9
|
3
|
1.5
|
|
Otitis/Otorrhea
|
0
|
0
|
3
|
1.5
|
|
Endotoxic Shock
|
1
|
1.4
|
2
|
1.0
|
|
Hematuria
|
0
|
0
|
2
|
1.0
|
|
Excoriation
|
0
|
0
|
2
|
1.0
|
Other clinical signs were reported but were
<0.5% of dogs.
Adverse reactions seen in a European field study
included ataxia, lethargy and injection site soreness in one dog treated
with CERENIA Injectable Solution.
CAUTION: Federal (USA) law restricts this
drug to use by or on the order of a licensed veterinarian.
DESCRIPTION: Maropitant is a neurokinin
(NK1) receptor antagonist that blocks the pharmacological
action of substance P in the central nervous system (CNS). Maropitant is
the non-proprietary designation for a substituted quinuclidine. The
empirical formula is C32H40N2O C6H8O7
H2O and the molecular weight 678.81. The chemical name is (2S,3S)-2-benzhydryl-N-(5-tert-butyl-2-methoxybenzyl)
quinuclidin-3-amine citrate monohydrate. Each mL of CERENIA Injectable
Solution contains 10 mg maropitant, 63 mg sulphobutylether-beta-cyclodextrin,
3.3 mg metacresol and water for injection.
Pharmacodynamics
Vomiting is a complex process coordinated
centrally by the emetic center which consists of several brainstem
nuclei (area postrema, nucleus tractus solitarius, dorsal motor nucleus
of the vagus) that receive and integrate sensory stimuli from central
and peripheral sources and chemical stimuli from the circulation and the
cerebro-spinal fluid. Maropitant is a neurokinin 1 (NK1)
receptor antagonist which acts by inhibiting the binding of substance P,
a neuropeptide of the tachykinin family. Substance P is found in
significant concentrations in the nuclei comprising the emetic center
and is considered the key neurotransmitter involved in emesis.1
By inhibiting the binding of substance P within the emetic center,
maropitant provides broad-spectrum effectiveness against neural
(central) and humoral (peripheral) causes of vomiting. In vivo
model studies in dogs have shown that maropitant has antiemetic
effectiveness against both central and peripheral emetogens including
apomorphine, cisplatin, and syrup of ipecac.
EFFECTIVENESS: In laboratory model
studies, CERENIA Injectable Solution administered at 1 mg/kg in Beagle
dogs reduced the number of emetic events associated with established
neural (central) and humoral (peripheral) stimuli. Following
administration of apomorphine (central emetic stimuli), vomiting was
observed in 16.7% (2 of 12) of dogs treated with CERENIA Injectable
Solution and 83.3% (10 of 12) of placebo-treated dogs. Following
administration of syrup of ipecac (peripheral emetic stimuli) vomiting
was observed in 25% (3 of 12) of dogs treated with CERENIA Injectable
Solution and in 100% (12 of 12) of dogs treated with placebo.
In a study of veterinary cancer patients, dogs
were treated with CERENIA Injectable Solution or placebo either 1 hour
prior to cisplatin (prevention) or after the first vomiting episode
following cisplatin (treatment) and monitored for 5 hours. In the groups
evaluated for prevention of vomiting, 94.9% (37/39) of the dogs
administered CERENIA Injectable Solution and 4.9% (2/41) of the dogs
administered placebo did not vomit. In the groups evaluated for
treatment, 21% (8/38) of the dogs administered CERENIA Injectable
Solution and 5.1% (2/39) of the dogs administered placebo had no further
episodes of vomiting following treatment.
Frequency Distribution of Numbers of Vomiting
Episodes For Treatment: Number of Vomiting Episodes Post Injection.
For Prevention: Total Number of Vomiting
Episodes.
|
Number of Vomiting Episodes
|
Dogs with Vomiting Episodes* (% of Dogs)
|
|
Treatment of Vomiting
|
Prevention of Vomiting
|
|
Placebo (n = 39**)
|
CERENIA (n = 38**)
|
Placebo (n = 41)
|
CERENIA (n = 39)
|
|
0
|
2 (5.1)
|
8 (21.1)
|
2 (4.9)
|
37 (94.9)
|
|
1
|
3 (7.7)
|
7 (18.4)
|
2 (4.9)
|
1 (2.6)
|
|
2
|
4 (10.3)
|
6 (15.8)
|
3 (7.3)
|
1 (2.6)
|
|
3
|
3 (7.7)
|
6 (15.8)
|
4 (9.8)
|
0 (0)
|
|
4
|
4 (10.3)
|
4 (10.5)
|
3 (7.3)
|
0 (0)
|
|
5
|
2 (5.1)
|
5 (13.2)
|
4 (9.8)
|
0 (0)
|
|
6
|
14 (35.9)
|
1 (2.6)
|
1 (2.4)
|
0 (0)
|
|
7
|
2 (5.1)
|
1 (2.6)
|
12 (29.3)
|
0 (0)
|
|
8
|
2 (5.1)
|
0 (0)
|
5 (12.2)
|
0 (0)
|
|
9
|
2 (5.1)
|
0 (0)
|
2 (4.9)
|
0 (0)
|
|
10
|
0 (0)
|
0 (0)
|
2 (4.9)
|
0 (0)
|
|
11
|
1 (2.6)
|
0 (0)
|
0 (0)
|
0 (0)
|
|
12
|
NA
|
NA
|
1 (2.4)
|
0 (0)
|
*Dogs that exhibited an unacceptable level of
vomiting (6 events) were withdrawn from the study and treated with
another antiemetic.
**There were initially 41 and 42 dogs treated
with either placebo or CERENIA Injectable Solution, respectively.
However, if a dog did not vomit following cisplatin therapy, it did not
receive a post-cisplatin treatment with either placebo or CERENIA, and
hence it was not considered in the therapeutic evaluation.
In a study of 275 canine patients presented to
veterinary hospitals with a history of acute vomiting, dogs were
initially administered CERENIA Injectable Solution or placebo on Day 0.
Following the initial dose, dogs allocated to the CERENIA group were
treated with either CERENIA Tablets at a minimum of 2 mg/kg orally or
Injectable Solution at 1 mg/kg subcutaneously once daily at the
discretion of the clinician. Dogs allocated to the placebo group were
treated using either an injectable placebo solution or placebo tablets
once daily at the discretion of the clinician. Of the 199 dogs included
in the analysis for effectiveness, 27 of 54 dogs (50%) in the placebo
group displayed vomiting at some time during the study and 31 of 145
dogs (21.4%) in the CERENIA treated group displayed vomiting during the
study period.
Percent of Vomiting for
Each Study Day, Based Upon Treatment and Route of Administration.
|
Days
|
Treatment
|
Route
|
# dogs
|
# vomited
|
% vomited
|
|
Day 0
|
Placebo (54)
|
SC
|
54
|
15
|
28%
|
|
CERENIA (145)
|
SC
|
145 (143*)
|
14
|
10%
|
|
Day 1
|
Placebo (45)
|
PO
|
22
|
3
|
14%
|
|
SC
|
23
|
16
|
70%
|
|
CERENIA (108)
|
PO
|
67
|
2
|
3%
|
|
SC
|
41
|
16
|
39%
|
|
Day 2
|
Placebo (16)
|
PO
|
7
|
2
|
29%
|
|
SC
|
9
|
6
|
67%
|
|
CERENIA (37)
|
PO
|
24
|
0
|
0%
|
|
SC
|
13
|
8
|
62%
|
|
Day 3
|
Placebo (6)
|
PO
|
2
|
0
|
0%
|
|
SC
|
4
|
1
|
25%
|
|
CERENIA (21)
|
PO
|
14
|
0
|
0%
|
|
SC
|
7
|
5
|
71%
|
|
Day 4
|
Placebo (2)
|
PO
|
1
|
0
|
0%
|
|
SC
|
1
|
1
|
100%
|
|
CERENIA (7)
|
PO
|
5
|
0
|
0%
|
|
SC
|
2
|
1
|
50%
|
|
Day 5
|
CERENIA (1)
|
SC
|
1
|
0
|
0%
|
*2 dogs administered CERENIA
were not observed on day 0. Their vomiting status was unknown. 143 was
used in the denominator for % vomited.
ANIMAL SAFETY: Laboratory and field
studies have demonstrated that CERENIA Injectable Solution is well
tolerated in dogs after subcutaneous administration.
Fifty six Beagle dogs (28 males and 28 females)
approximately 16 weeks of age were administered CERENIA Injectable
Solution subcutaneously once daily for 15 days at 0, 1, 3, and 5 mg/kg.
There were 8 dogs (4 males and 4 females) in the 1 mg/kg group and 16
dogs (8 males and 8 females) in all other groups. The primary
treatment-related findings were injection site reactions. Swelling,
thickened skin, or pain at one or more of the injection sites on one or
more days of the study was observed in 6 of 16 animals treated with 3
mg/kg/day and 5 of 16 animals treated with 5 mg/kg/day. Additionally,
the activated partial thromboplastin time (APTT) was prolonged (67.5
seconds, reference range 9-15 seconds) in one male dog in the 1 mg/kg
group on study day 15. Relationship of the prolonged APTT to drug
administration could not be determined.
Beagle dogs approximately 8 weeks of age were
administered CERENIA Injectable Solution subcutaneously once daily for
15 days at 0, 1, 3, and 5 mg/kg using a protocol similar to the previous
study. A dose dependent increase in frequency and severity of bone
marrow hypoplasia was observed histologically. One placebo treated dog
died on day 14 of the study and was diagnosed with suppurative
pancreatitis and esophagitis. Interpretation of the study results is
complicated by the health status of study animals. Dogs used in the
study were weaned early, minimally acclimated to the test facility, and
many of the dogs in the study tested positive for coccidia.
In US field studies in veterinary patients,
CERENIA Injectable Solution and Tablets were well tolerated in dogs
presenting with various clinical conditions including parvovirus,
gastroenteritis, and renal disease. There were no notable differences in
mean laboratory values between CERENIA-treated and placebo-treated
patients.
CERENIA Injectable Solution was used safely in
dogs receiving other frequently used veterinary products such as fluid
and electrolyte replacement solutions, antimicrobial agents, vaccines,
antacids, and antiparasitic agents.
STORAGE CONDITIONS: CERENIA Injectable
Solution should be stored at controlled room temperature 20-25°C
(68-77°F) with excursions between 15-30°C (59-86°F). Use within 28 days
of first vial puncture.
HOW SUPPLIED: CERENIA Injectable Solution
is supplied in 20 mL amber glass vials. Each mL contains 10 mg of
maropitant as maropitant citrate.
Manufacturer:
Pfizer Animal Health