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CERENIA™ INJECTABLE SOLUTION
Pfizer Animal Health
For subcutaneous injection in dogs only
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
The chemical structure of maropitant citrate is:
INDICATIONS: 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.
CERENIA Injectable Solution is recommended for use in dogs 16 weeks and older.
Dog body weight
Dose Volume (mL)
2.3 - 4.4
1.1 - 2.0
4.5 - 6.6
2.1 - 3.0
6.7 - 8.8
3.1 - 4.0
8.9 - 11.0
4.1 - 5.0
11.1 - 16.5
5.1 - 7.5
16.6 - 22.0
7.6 - 10.0
22.1 - 33.0
10.1 - 15.0
33.1 - 44.0
15.1 - 20.0
44.1 - 66.0
20.1 - 30.0
66.1 - 88.0
30.1 - 40.0
88.1 - 110.0
40.1 - 50.0
110.1 - 132.0
50.1 - 60.0
CERENIA Injectable Solution may be used interchangeably
with CERENIA Tablets for once daily dosing for the prevention of acute
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
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
Frequency of Adverse Reactions by Treatment
Injection site reaction (swelling, pain upon injection)
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:
Death during study
Euthanized during study
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.
For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Pfizer Animal Health at 1-800-366-5288.
The pharmacokinetic characterization associated with
maropitant after oral (PO) or subcutaneous (SC) administration in adult
Beagle dogs is provided in the table below.
Pharmacokinetic Parameters in Beagle Dogs (Mean ±SD or range)
SC at 1 mg/kg (n=6)
PO at 2 mg/kg (n=8)
PO at 8 mg/kg (n=8)
The absolute bioavailability of maropitant was much
higher following SC injection (91% at 1 mg/kg) than after PO
administration (24% at 2 mg/kg). Oral bioavailability may be
underestimated due to the presence of nonlinear kinetics and the
resulting longer T1/2 seen after
intravenous (IV) administration. Although hepatic first-pass metabolism
contributed to the relatively low bioavailability after an oral dose,
prandial status does not significantly affect the extent of oral
bioavailability. Greater than dose-proportional drug exposure can be
expected with an increase in dose (1-16 mg/kg PO). Systemic clearance
of maropitant following IV administration was 970, 995, and 533
mL/hr/kg at doses of 1, 2 and 8 mg/kg, respectively. An accumulation
ratio of 1.5 was observed following once-daily use of maropitant for
five consecutive days at 1 (SC) or 2 mg/kg (PO). Urinary recovery of
maropitant and its major metabolite was minimal (<1% each). The
hepatic metabolism of maropitant involves two cytochrome P-450
isoenzymes: CYP2D15 and CYP3A12. Based on in vitro
enzyme kinetics data, it is believed that the non-linear kinetics may
be partially associated with saturation of the low capacity enzyme
(CYP2D15). However as doses increase (20-50 mg/kg PO), dose
proportionality is re-established. Based upon in vitro
enzyme kinetics, involvement of a high capacity enzyme (CYP3A12) may
contribute to this return to dose linearity. Plasma protein binding of
maropitant was high (99.5%).
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.
1Diemunsch P, Grelot L. Potential of substance P antagonists as antiemetics. [Review] [60 refs]. Drugs. 2000;60:533-46.
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)
*Dogs that exhibited an unacceptable level of vomiting
(6 events) were withdrawn from the study and treated with another
**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
Percent of Vomiting for Each Study Day, Based Upon Treatment and Route of Administration.
*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.
US Patents: See US 6,222,038; US 6,255,320
NADA #141-263, Approved by FDA
Distributed by: Pfizer Animal Health, Div. of Pfizer Inc, NY, NY 10017
Made in France
88 1185 0
NAC No.: 36902390