Cerenia Injection (Canada)

This page contains information on Cerenia Injection for veterinary use.
The information provided typically includes the following:
  • Cerenia Injection Indications
  • Warnings and cautions for Cerenia Injection
  • Direction and dosage information for Cerenia Injection

Cerenia Injection

This treatment applies to the following species:
Manufacturer: Zoetis

maropitant citrate injection

Veterinary Use Only

sterile

antiemetic for dogs and cats

DIN 02299542

Description

Maropitant is a potent and selective neurokinin (NK1) receptor antagonist that blocks the pharmacological action of substance P in the CNS. Maropitant is the non-proprietary designation for a substituted quinuclidine. The chemical name is (2S,3S) - N - [[5 - (1,1 - dimethylethyl) - 2 - methoxyphenyl]methyl] - 2 - (diphenylmethyl) - 1 - azabicyclo[2.2.2]octan - 3 - amine 2-hydroxy-1,2,3- propanetricarboxylate monohydrate.

The chemical structure of maropitant citrate is:

Each mL of CERENIA® injection contains 10 mg of maropitant (as maropitant citrate) as the medicinal ingredient and 3.3 mg metacresol as a preservative.

Cerenia Injection Indications

DOGS: For the symptomatic treatment of acute vomiting (e.g. parvovirus infection, gastro-enteritis and pancreatitis) and the prevention of vomiting associated with chemotherapy.

CATS: For the symptomatic treatment of acute vomiting.

Dosage and Administration

The recommended dosage for subcutaneous administration of CERENIA injection in dogs and cats is 1 mg/kg equal to 1 mL/10 kg body weight.

DOGS: For the symptomatic treatment of acute vomiting in dogs 10 weeks of age and older, administer CERENIA injection once daily for up to 5 days.

CERENIA injection may be used interchangeably with CERENIA tablets for once daily dosing of the acutely vomiting dogs. The dose is different depending on the formulation.

For the prevention of vomiting associated with chemotherapy in dogs 16 weeks of age and older, the injection should be given 1 hour before chemotherapy.

CATS: For the symptomatic treatment of acute vomiting in cats 16 weeks of age and older, administer CERENIA injection once daily for up to 5 days.

CERENIA injection may be administered at room temperature (15-30°C) or refrigerated temperature (2-8°C). Injecting at refrigerated temperature may reduce the pain response associated with the injection.

CONTRAINDICATIONS: CERENIA injection is contraindicated in dogs and cats suspected of having a gastrointestinal obstruction or toxin ingestion. Immediate treatment should be directed at addressing the underlying cause not the sign of vomiting.

CAUTIONS: For subcutaneous injection only. Safety in dogs and cats used for breeding, pregnant, or lactating bitches and queens and puppies less than 10 weeks of age or kittens less than 16 weeks of age has not been established. See the Animal Safety section for complete information. Emesis may be associated with serious, severely debilitating conditions, and therefore appropriate diagnostic evaluations should be employed. Hypovolemia in combination with maropitant may increase the risk for hypotension; all dogs and cats with ongoing emesis should receive rehydration therapy. CERENIA injection should be used with caution in dogs and cats with bradycardia or underlying heart disease since maropitant may increase the risk of arrhythmias. Maropitant is metabolized in the liver and therefore should be used with caution in dogs and cats with hepatic disease. Maropitant is a highly protein bound drug; interactions of injectable maropitant with other drugs may result in increased concentrations of maropitant; interactions with maropitant injectable have not been thoroughly investigated in dogs and cats. Hypoproteinemic dogs and cats being treated with maropitant should be monitored closely; if adverse effects are seen, treatment should be discontinued. If maropitant therapy has not been effective after 3 days of use, alternative treatment to control vomiting should be pursued. The concurrent use of maropitant with other antiemetic agents has not been assessed in dogs and cats. Food consumption and weight gain of puppies being treated with CERENIA should be closely monitored. Anorexia and weight loss may occur. CERENIA causes dose related decreases in appetite and body weight. In puppies younger than 11 weeks of age, histological evidence of bone marrow hypocellularity was observed at higher frequency and greater severity in puppies treated with CERENIA compared to control puppies. In puppies, 16 weeks and older, bone marrow hypocellularity was not observed (see Animal Safety).

Warnings

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.

Adverse Reactions:

Dogs And Cats

Pain at injection site may occur. Administration of CERENIA injection at refrigerated temperatures may mitigate this response (see DOSAGE AND ADMINISTRATION).

- In cats, moderate to severe response to injection is very commonly observed (in approximately one third of cats).

In very rare cases, anaphylactic type reactions (allergic edema, urticaria, erythema, collapse, dyspnea, pale mucous membranes) may occur. Lethargy, anorexia and ataxia have been observed shortly after the use of the product and generally resolve within 24 hours without treatment or after the underlying cause for the vomiting is corrected.

Post Market Experience

The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse reactions are reported and it is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data. The following adverse reactions are listed in decreasing order of reporting frequency (by body system):

- Application site - injection site pain, injection site oedema

- Systemic -lethargy, anorexia

- Immune - allergic oedema, urticaria, anaphylaxis

- Neurological - ataxia, muscle tremor, convulsion

- Digestive tract - vomiting, hypersalivation, diarrhea

- Skin and appendages - erythema, pruritus

- Behavioural - vocalization, hyperactivity

The following adverse reactions have been observed in field studies:

DOGS: In a U.S. 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 injection 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

% occurrence

# dogs

% occurrence

Diarrhea

1

2.4

6

7.8

Anorexia

0

0

4

5.2

Injection site reaction (swelling pain upon injection)

0

0

3

4

Lethargy

1

2.4

2

2.6

The following adverse reactions were reported during the course of a U.S. field study for the prevention and treatment of acute vomiting in dogs treated with 1.0 mg/kg CERENIA injection subcutaneously and/or CERENIA tablets at 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

% occurrence

# dogs

% occurrence

Death during study

4

5.8

10

4.9

Euthanized during study

0

0

2

1

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

Hematuria

0

0

2

1

Excoriation

0

0

2

1

Lack of Efficacy

6

8.7

5

2.4

Other clinical signs were reported but were <0.5% of dogs.

CATS: The following adverse reactions were reported during the course of a U.S. field study for the treatment of vomiting in cats treated with 1.0 mg/kg CERENIA injection subcutaneously once daily for up to five consecutive days:

Frequency of Adverse Reactions by Treatment

Adverse Reaction

Placebo (n=62)

CERENIA (n=133)

# cats

% occurrence

# cats

% occurrence

Moderate Response to Injection1,2

1

1.6

30

22.6

Significant Response to Injection1,3

1

1.6

15

11.3

Fever/Pyrexia

2

3.2

2

1.5

Dehydration

0

0

3

2.3

Lethargy

0

0

2

1.5

Diarrhea

4

6.5

2

1.5

Conjunctivitis

0

0

2

1.5

1 The clinician observed and graded each cat’s response to injection.

2 Cat objected to the injection by retreating and vocalizing

3 Cat objected to the injection by retreating, hissing, scratching, and vocalization

The adverse events with occurrence of <1% include abdominal pain, anorexia, hematochezia, hematuria and hypersalivation

Clinical Pharmacology

Pharmacokinetics:

DOGS: In a series of studies undertaken to characterize the pharmacokinetics of maropitant in dogs following oral (PO) or subcutaneous (SC) administration, the absolute bioavailability of maropitant was much higher (90.7%) following subcutaneous injection than after oral administration (23.7% at the 2 mg/kg dose). Feeding status had no effect on oral bioavailability. Hepatic first-pass metabolism contributed to the relatively low bioavailability of maropitant following oral administration. Maximum plasma drug concentration (Cmax) occurred at 0.75 hour (tmax) after subcutaneous administration at 1 mg/kg, and at 1.9 hours (mean tmax values) after oral administration of a 2 mg/kg dose. The apparent elimination half-life of maropitant was 8.84 hours after dosing at 1 mg/kg (SC). The apparent elimination half-life of maropitant determined after one oral dose (2 mg/kg, PO) was 4.03 hours. After 5 days of dosing (2 mg/kg, PO) the elimination half-life increases. Systemic clearance of maropitant following intravenous (IV) administration was 970, 995, and 533 mL/h.kg at doses of 1, 2 and 8 mg/kg, respectively, thus confirming the non-linear disposition of maropitant within the 2-8 mg/kg dose range. Also, non-proportional kinetics of orally administered maropitant was established at doses ranging from 2 to 16 mg/kg. Dose linearity was demonstrated for maropitant following SC administration at 0.5x, 1x, and 2x the intended SC use dose (i.e., 0.5, 1 and 2 mg/kg). Following once-daily administration of maropitant for five consecutive days at 1 mg/kg (SC) or 2 mg/kg (PO), accumulation occurred with the mean AUC0-24h for the last dose ranging between 142% and 151% that of the first dose. Urinary recovery of maropitant and its major metabolite CJ-18,518 was minimal (<1%). The hepatic metabolism of maropitant involves two cytochrome P-450 isoenzymes: CYP2D15 and CYP3A12. The nonlinear kinetics observed at 2X the intended oral use dose is likely linked to saturation of the low capacity CYP2D15; however, as doses increase (20-50 mg/kg P.O.), involvement of the CYP3A12-mediated high capacity process tends to re-establish linearity. Plasma protein binding of maropitant was high (>99%). There were no clinically significant pharmacokinetic differences between sexes. Based on differences in trough plasma concentrations from a single study, the exposure of 10 week old puppies to maropitant may be lower than that observed in adult dogs, particularly after dosed with 1 or 2 mg/kg.

CATS: The pharmacokinetic profile of maropitant when administered as a single subcutaneous dose of 1 mg/kg body weight to cats was characterized by a maximum concentration (Cmax) in plasma of approximately 165 ng/mL; this was achieved on average 0.32 hours (19 min) post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t1/2) of 16.8 hours and area under the curve (AUC0-∞) οf 3490 hr.ng/mL. There appears to be an age-related effect on the pharmacokinetics of maropitant in cats with kittens (16 weeks) having higher clearance than adults. The bioavailability of maropitant after subcutaneous administration in cats was 91.3%. The volume of distribution at steady-state (Vss) determined after intravenous administration at 0.25 mg/kg ranged from 2.27 to 3.80 L/kg. Maropitant displays linear kinetics when administered subcutaneously within the 0.25 - 3 mg/kg dose range. Following repeated subcutaneous administration of once-daily doses of 1 mg/kg bodyweight for five consecutive days, accumulation was 250%. Renal and fecal clearances are minor routes of elimination for maropitant, with less than 1% of a 1 mg/kg subcutaneous dose appearing in the urine or feces as maropitant. For the major metabolite 10.4% of the maropitant dose was recovered in urine and 9.3% in feces. Maropitant undergoes cytochrome P450 (CYP) metabolism in the liver. CYP1A and CYP3A-related enzymes were identified as the feline isoforms involved in the hepatic biotransformation of maropitant. Plasma protein binding of maropitant in cats was estimated to be 99.1%.

CERENIA injection is formulated using sulphobutylether-β-cyclodextrin (SBECD), which exhibits enhanced binding to maropitant at refrigerated temperatures. The enhanced binding affinity reverses rapidly upon warming. Therefore, although the initial rate of systemic drug absorption may vary as a function of injected product temperature, based upon product pharmacokinetics, these changes are not expected to influence product systemic safety or effectiveness.

Pharmacodynamics: Emesis 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. By inhibiting the binding of substance P within the emetic center, maropitant provides broad-spectrum efficacy against neural (central) and humoral (peripheral) causes of emesis. A variety of in vitro assays have demonstrated that maropitant displays potent and selective binding at the NK1 receptor with dose-dependent functional antagonism of substance P activity. In vivo model studies in dogs have shown that maropitant has potent antiemetic efficacy against central and peripheral emetogens including apomorphine, cisplatin and syrup of ipecac.

ANIMAL SAFETY: Laboratory studies and clinical field evaluations have demonstrated that CERENIA injection is well tolerated in dogs and cats after subcutaneous administration. Pain at injection site may occur.

DOGS: In laboratory studies, CERENIA injection was well tolerated when administered subcutaneously to healthy 16-week-old dogs for 15 days at up to 5 mg/kg. One dog in the 1 mg/kg group had a focal haemorrhage associated with the injection site, 4/8 dogs in the 3 mg/kg group had injection site reactions which included subcutaneous edema and haemorrhage and 6/8 dogs in the 5 mg/kg group had injection site reactions including haemorrhage and edema. 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 10 weeks of age were administered either placebo tablets for 2 days, CERENIA tablets at 8 mg/kg for 2 days, placebo (saline) subcutaneously (SC) for 5 days, CERENIA injectable Solution at 1 mg/kg SC for 5 days, or CERENIA tablets at 2 mg/kg for 5 days (8 dogs in each dose group). Mild pain associated with injection was noted in more dogs and lasted longer in dogs that received maropitant injections compared to saline. Males administered CERENIA at 8 mg/kg orally for 2 days had a decrease in food consumption. Body weight and food consumption were variable throughout the 4 week acclimatization period. Two dogs that received 8 mg/kg maropitant orally for 2 days were below the reference range for reticulocyte counts. Decreases in reticulocyte counts were also seen in 4 (of 8) placebo treated dogs (SC saline for 5 days). Hypocellular femoral bone marrow described as “minimal” was seen in 1 male that received 1 mg/kg maropitant SC for 5 days; reticulocyte counts were not available for this dog. In the 10 week old puppies, the food consumption and body weights were variable in many puppies throughout the study. Two puppies in the 2 mg/kg oral group had decreased food consumption; one puppy consumed 13% less food and the second puppy consumed 18% less food. The decreased food consumption was not associated with a decrease in body weight in either puppy.

Beagle dogs approximately 8 weeks of age were administered CERENIA injection subcutaneously once daily for 15 days at 0, 1, 3 and 5 mg/kg using a protocol similar to the study in 16 week old dogs. The primary treatment-related findings were pain upon administration of injections and dose-dependent minimal to moderate injection site irritation and swelling. Weight gain was variable in individual dogs across all treatment groups, with some dogs experiencing a weight loss during the study. Bone marrow hypocellularity was observed histologically, affecting 1 to 3 of 8 dogs per dose group including placebo, and was highly correlated with weight loss or abnormally low weight gain. The severity of bone marrow hypocellularity was higher in CERENIA treatments than controls, but there were no correlating changes in peripheral hematology data. 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.

CERENIA was used in dogs receiving other frequently used veterinary products such as fluid and electrolyte replacement solutions, antimicrobial agents, vaccines, antacids, and antiparasitic agents. There were no notable differences in mean laboratory values between CERENIA-treated and placebo-treated dogs.

CATS: Thirty-two domestic short hair cats (16 males and 16 females) approximately 16 weeks of age were administered CERENIA injection subcutaneously once daily for 15 days at 0, 1, 3, and 5 mg/kg. There were 8 cats (4 males and 4 females) in each group. Treatment-related dose dependent findings were pain associated with administration of CERENIA injection, increased restraint during injections, and injection site heat, pain, redness and firmness. Pain on injection and increased restraint were observed in 5% of placebo-treated cats, 50% of CERENIA injection-treated cats at 1 mg/kg, and 75% of CERENIA injection-treated cats at 3 and 5 mg/kg. Injection site firmness > 10 mm in diameter at one or more of the injection sites on one or more days of the study was observed in 1 of 8 cats treated at 1 mg/kg, 7 of 8 cats treated at 3 mg/kg, and 7 of 8 cats treated at 5 mg/kg. There was a statistically significant reduction (p = 0.0171) in food intake at 5 mg/kg compared to placebo cats. One cat at 5 mg/kg was lethargic on days 12, 13 and 14 of the study. One cat at 3 mg/kg on days 10 and 11, and 1 cat at 3 mg/kg and 5 mg/kg on day 12 had increased skin turgor. At necropsy, there were no treatment related gross findings. Histopathologic evaluation of injection sites showed there was a dose dependent inflammatory response.

EFFICACY:

DOGS: In laboratory model studies, CERENIA injection significantly reduced the number of emetic events associated with established neural (central) and humoral (peripheral) stimuli.

In vivo studies in dogs demonstrated the antiemetic efficacy of maropitant against central and peripheral emetics including apomorphine, cisplatin and syrup of ipecac. Following administration of syrup of ipecac emesis was observed in 25% (3 of 12) of dogs treated with CERENIA and in 100% (12 of 12) of dogs treated with placebo. Following administration of apomorphine, emesis was observed in 16.7% (2 of 12) of dogs treated with CERENIA and 83.3% (10 of 12) of placebo-treated dogs.

In a study of veterinary cancer patients in the United States, dogs were treated with CERENIA injection or placebo was administered 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 injection and 4.9% (2/41) of the dogs administered placebo did not vomit. In the groups evaluated for treatment of vomiting, 21% (8/38) of the dogs administered CERENIA injection and 5.1% (2/39) of the dogs administered placebo had no further episodes of vomiting following treatment.

In a U.S. study of 275 canine patients presented to veterinary hospitals with a history of acute vomiting, dogs were initially administered CERENIA injection 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 with CERENIA injection 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 252 dogs included in the analysis for effectiveness, 32 of 64 dogs (50%) in the placebo group displayed vomiting at some time during the study and 41 of 188 dogs (21.8%) 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 (63)

SC

63

18

29%

CERENIA (182)

SC

182

18

10%

Day 1

Placebo (64)

PO

26

4

15%

SC

27

17

63%

CERENIA (182)

PO

96

3

3%

SC

46

17

37%

Day 2

Placebo (63)

PO

13

2

15%

SC

9

6

67%

CERENIA (170)

PO

40

0

0%

SC

14

9

64%

Day 3

Placebo (55)

PO

2

0

0%

SC

5

1

20%

CERENIA (165)

PO

16

0

0%

SC

6

4

67%

Day 4

Placebo (19)

PO

1

0

0%

SC

1

1

100%

CERENIA (73)

PO

7

1

14%

SC

2

1

50%

In this study, CERENIA injection and tablets were well tolerated in dogs presenting with various clinical conditions.

Number of Dogs with Emesis Due to Various Clinical Conditions Treated in U.S. Clinical Veterinary Patient Study with CERENIA tablets and injection

 

CERENIA® (n = 206)

Placebo (n = 69)

Parvoviral enteritis

50

22

Gastroenteritis and related1

93

24

Acute pancreatitis

20

8

Renal disease2

4

4

Hepatic disease3

6

0

1 This medical condition included dietary gastritis, dietary indiscretion, digestive tract bacterial and viral infections, enteritis, gastritis, gastroenteritis, and haemorrhagic, parasitic and viral gastroenteritis

2 This medical condition included acute renal failure, decompensated chronic renal failure, miscellaneous renal disorder NOS and pyelonephritis

3 This medical condition included hepatic disease and hepatitis

CATS: In a laboratory model study, CERENIA injection administered to cats at a dosage of 1.0 mg/kg, prevented vomiting for a full 24-hour period. Following administration of the emetogen xylazine 23 hours after antiemetic treatment, 33% (4 of 12) of CERENIA injection-treated cats vomited once each while 100% (12/12) of placebo-treated cats each vomited from 1-3 times.

In a U.S. field study of 195 feline patients diagnosed with gastroenteritis, pancreatitis, inflammatory bowel disease, neoplastic disease and hepatic lipidosis presented to veterinary hospitals with a history of acute vomiting, cats were treated with CERENIA injection or placebo (in a ratio of 2:1) and observed in the veterinary hospital for 24 hours for the presence of an emetic event(s) defined as the observation of the act of vomiting or the presence of vomitus. Cats could continue antiemetic treatment every 24 hours for up to five consecutive days at the discretion of the clinician. Of 182 cats included in the analysis for effectiveness, in the first 24 hours post treatment, two CERENIA injection-treated cats (1.6%) vomited one time each and 12 placebo-treated cats (20.3%) vomited a combined total of 20 times.

Percent of Cats Vomiting for Each Study Day by Treatment

Study Day

Treatment

# cats

# vomited

% vomited

Day 0

Placebo

59

12

20.3

CERENIA injection

123

2

1.6

Day 1

Placebo

21

5

23.8

CERENIA injection

35

1

2.9

Day 2

Placebo

9

2

22.2

CERENIA injection

10

0

0.0

Day 3

Placebo

5

0

0.0

CERENIA injection

6

0

0.0

Day 4

Placebo

3

0

0.0

CERENIA injection

2

0

0.0

Storage

Store at controlled room temperature 20-25°C with excursions between 15-30°C. After first vial puncture, CERENIA injection should be stored at refrigerated temperature 2-8°C. Use within 90 days of first vial puncture. Stopper may be punctured a maximum of 25 times.

PRESENTATION: CERENIA injection is available in 20 mL amber glass vials.

® Registered Trade-mark of Pfizer Products Inc.; Pfizer Canada Inc., licensee.

© Pfizer Canada Inc.

Pfizer Animal Health, Pfizer Canada Inc., Kirkland QC H9J 2M5

Nov 15, 2012

NAC No.: 11983423

ZOETIS CANADA
16,740 TRANS-CANADA HIGHWAY, KIRKLAND, QC, H9H 4M7
Order Desk:   800-663-8888
Technical Services Canada:   800-461-0917
Technical Services USA:   800-366-5288
Website:   www.zoetis.ca
Every effort has been made to ensure the accuracy of the Cerenia Injection information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.

Copyright © 2014 North American Compendiums. Updated: 2014-09-05

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