Summary of medicine characteristics - Cerenia
-
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active substance:
Each tablet contains 16 mg, 24 mg, 60 mg or 160 mg maropitant as maropitant citrate monohydrate.
Excipients:
Each tablet contains 0.075% w/w Sunset Yellow (E110) as a colorant.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Pale orange tablet.
The tablets have a score line allowing the tablet to be halved, with the letters “MPT” and figures denoting the quantity of maropitant on one side, the reverse side is blank.
4. CLINICAL PARTICULARS4.1 Target species
Dogs.
-
4.2 Indications for use, specifying the target species
- • For the prevention of nausea induced by chemotherapy.
- • For the prevention of vomiting induced by motion sickness.
- • For the prevention and treatment of vomiting, in conjunction with Cerenia solution for injection and in combination with other supportive measures.
4.3 Contraindications
None.
-
4.4 Special warnings for each target species
Vomiting can be associated with serious, severely debilitating conditions including gastrointestinal obstructions; therefore, appropriate diagnostic evaluations should be employed.
Cerenia tablets have been shown to be effective in the treatment of emesis, however where the frequency of vomiting is high, orally administered Cerenia may not be absorbed before the next vomiting event occurs. It is therefore recommended to initiate the treatment of emesis with Cerenia solution for injection.
Good veterinary practice indicates that antiemetics should be used in conjunction with other veterinary and supportive measures, such as dietary control and fluid replacement therapy while addressing the underlying causes of the vomiting. The safety of maropitant during treatment beyond 5 days has not been explored in the target population (i.e. young dogs suffering from viral enteritis). In case treatment for a longer period than 5 days is regarded as necessary, careful monitoring of potential adverse events should be implemented.
-
4.5 Special precautions for use
Special precautions for use in animals
The safety of the veterinary medicinal product has not been established in dogs less than 16 weeks of age for the 8 mg/kg dose (motion sickness), and in dogs less than 8 weeks of age for the 2 mg/kg dose (vomiting) as well as in pregnant or lactating bitches. Use only according to the benefit-risk assessment by the responsible veterinarian.
Maropitant is metabolised in the liver and therefore should be used with caution in patients with hepatic disease. As maropitant is accumulated in the body during a 14-day treatment period due to metabolic saturation, careful monitoring of liver function in addition to any adverse events should be implemented during long term treatment.
Cerenia should be used with caution in animals suffering from or with predisposition for cardiac diseases as maropitant has affinity to Ca- and K-ion channels. Increases of approximately 10% in the QT interval of the ECG were observed in a study on healthy beagle dogs administered 8 mg/kg orally; however, such an increase is unlikely to be of clinical significance.
Special precautions to be taken by the person administering the veterinary medicinal product to animals
People with known hypersensitivity to maropitant should administer the veterinary medicinal product with caution.
Wash hands after use. In case of accidental ingestion seek medical advice immediately and show the package leaflet or the label to the physician.
-
4.6 Adverse reactions (frequency and seriousness)
Incidents of pre-travel vomiting, usually within two hours post-dosing were commonly reported after administration of the 8 mg/kg dose.
Lethargy has been reported in very rare cases, based on post-marketing safety experience.
The frequency of adverse reactions is defined using the following convention:
-
– very common (more than 1 in 10 animals treated displaying adverse reaction(s))
-
– common (more than 1 but less than 10 animals in 100 animals treated)
-
– uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
-
– rare (more than 1 but less than 10 animals in 10,000 animals treated)
-
– very rare (less than 1 animal in 10,000 animals treated, including isolated reports).
-
4.7 Use during pregnancy, lactation or lay
Use only according to the benefit-risk assessment by the responsible veterinarian, because conclusive reproductive toxicity studies have not been conducted in any animal species.
4.8 Interaction with other medicinal products and other forms of interaction
Cerenia should not be used concomitantly with Ca-channel antagonists as maropitant has affinity to Ca-channels.
Maropitant is highly bound to plasma proteins and may compete with other highly bound drugs.
-
4.9 Amounts to be administered and administration route
For oral use.
For motion sickness, a light meal or snack before dosing is recommended; prolonged fasting before administration should be avoided. However, Cerenia tablets should not be administered wrapped or encapsulated in food as this may delay dissolution of the tablet and consequently the onset of efficacy.
Dogs should be carefully observed following administration to ensure that each tablet is swallowed.
For the prevention of nausea induced by chemotherapy and treatment and prevention of vomiting (except motion sickness), (only for dogs 8 weeks of age or older).
To treat or prevent vomiting, Cerenia tablets should be administered once daily, at a dose of 2 mg maropitant per kg bodyweight, using the number of tablets given in the table below. Tablets are breakable along the score line on the tablet.
To prevent vomiting, tablets should be given more than 1 hour in advance. The duration of the effect is approximately 24 hours and, therefore, tablets can be given the night before administration of an agent that may cause emesis (e.g. chemotherapy).
Cerenia can be used to treat or prevent vomiting either as tablets or as solution for injection administered once daily. Cerenia solution for injection may be administered for up to five days and Cerenia tablets for up to fourteen days.
| Prevention of nausea induced by chemotherapy Treatment and prevention of vomiting (except motion sickness) | |
| Dog body weight | Number of tablets |
| (kg) | 16 mg | 24 mg | 60 mg |
| 3.0–4.0* | 72 |
| 4.1–8.0 | 1 |
| 8.1–12.0 | 1 |
| 12.1–24.0 | 2 |
| 24.1–30.0 | 1 |
| 30.1–60.0 | 1 2 |
* Correct dose for dogs of less than 3 kg cannot be accurately achieved.
For prevention of vomiting induced by motion sickness, (only for dogs 16 weeks of age or older)
To prevent vomiting induced by motion sickness, Cerenia tablets should be administered once daily, at a dose of 8 mg maropitant per kg bodyweight, using the numbers of tablets given in the table below. Tablets are breakable along the score line on the tablet.
Tablets should be administered at least one hour before starting the journey. The anti-emetic effect persists for at least 12 hours, which for convenience may allow administration the night before early morning travel. Treatment may be repeated for a maximum of two consecutive days.
| Prevention of motion sickness | ||||
| Dog body weight (kg) | Number of tablets | |||
| 16 mg | 24 mg 1 | 60 mg | I 160 mg | |
| 1.0–1.5 | / | |||
| 1.6–2.0 | 1 | |||
| 2.1–3.0 | 1 | |||
| 3.1–4.0 | 2 | |||
| 4.1–6.0 | 2 | |||
| 6.1–7.5 | 1 | |||
| 7.6–10.0 | / | |||
| 10.1–15.0 | 2 | |||
| 15.1–20.0 | 1 | |||
| 20.1–30.0 | 1/ | |||
| 30.1–40.0 | 2 | |||
| 40.1–60.0 | 1 3 | |||
As the pharmacokinetic variation is large and maropitant accumulates in the body after once daily repeated administration, lower doses than recommended might be sufficient in some individuals and when repeating the dose.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
Cerenia tablets were well tolerated when administered for 15 days at dosages up to 10 mg/kg bodyweight per day.
Clinical signs including vomiting on first administration, excess salivation and watery faeces have been observed when the product has been administered at doses in excess of 20 mg/kg.
-
4.11 Withdrawal period(s)
Not applicable.
5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: Antiemetics.
ATCvet code: QA04AD90.
Maropitant is a potent and selective neurokinin (NK-1) receptor antagonist, which acts by inhibiting the binding of substance P, a neuropeptide of the tachykinin family, in the CNS.
5.1 Pharmacodynamic properties
Vomiting is a complex process coordinated centrally by the emetic centre. This centre 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 centre and is considered the key neurotransmitter involved in vomiting. By inhibiting the binding of substance P within the emetic centre, maropitant is effective against neural and humoral (central and peripheral) causes of vomiting. A variety of in vitro assays have demonstrated that maropitant binds selectively at the NK1 receptor with dose-dependent functional antagonism of substance P activity. In vivo studies in dogs demonstrated the anti-emetic efficacy of maropitant against central and peripheral emetics including apomorphine, cisplatin and syrup of ipecac.
Maropitant is non-sedative and should not be used as a sedative in motion sickness.
Maropitant is effective against vomiting. Signs of nausea including excessive salivation and lethargy might remain during treatment.
-
5.2 Pharmacokinetic particulars
The pharmacokinetic profile of maropitant when administered as a single oral dose of 2 mg/kg body weight to dogs was characterised by a maximum concentration (Cmax) in plasma of approximately 81 ng/ml; this was achieved within 1.9 hours post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t0.5) of 4.03 hours.
At a dose of 8 mg/kg, Cmax of 776 ng/ml was reached at 1.7 hours post-dosing. The elimination halflife at 8 mg/kg was 5.47 hours.
The inter-individual variation in kinetics may be large, up to 70 CV% for AUC.
During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.
Estimates for the oral bioavailability of maropitant were 23.7% at 2 mg/kg and 37.0% at 8 mg/kg. The volume of distribution at steady-state (Vss) determined after intravenous administration at 1–2 mg/kg ranged from approximately 4.4 to 7.0 l/kg. Maropitant displays non-linear pharmacokinetics (AUC increases more than proportionally with increasing dose) when administered orally within the 1–16 mg/kg dose range.
Following repeated oral administration for five consecutive days at a daily dose of 2 mg/kg, accumulation was 151%. Following repeated oral administration for two consecutive days at a daily dose of 8 mg/kg, accumulation was 218%. Maropitant undergoes cytochrome P450 (CYP) metabolism in the liver. CYP2D15 and CYP3A12 were identified as the canine isoforms involved in the hepatic biotransformation of maropitant.
Renal clearance is a minor route of elimination, with less than 1% of an 8 mg/kg oral dose appearing in the urine as either maropitant or its major metabolite. Plasma protein binding of maropitant in dogs is more than 99%.
6. PHARMACEUTICAL PARTICULARS6.1 List of excipients
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate
Microcrystalline cellulose
Sunset Yellow (E110) as a colorant
6.2 Major incompatibilities
Not applicable.
6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 3 years.
Shelf life of half tablets: 2 days.
6.4 Special precautions for storage
This veterinary medicinal product does not require any special storage conditions.
An unused half tablet should be returned to the opened blister and kept within the outer cardboard.
-
6.5 Nature and composition of immediate packaging
Cardboard box containing one aluminium-aluminium blister pack, each containing four tablets per pack.
Cerenia tablets are available in 16 mg, 24 mg, 60 mg and 160 mg strength.
-
6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Zoetis Belgium SA
Rue Laid Burniat 1
1348 Louvain-la-Neuve
BELGIUM
8. MARKETING AUTHORISATION NUMBER(S)
EU/2/06/062/001–004
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 29/09/2006.
Date of last renewal: 29/09/2011.
10. DATE OF REVISION OF THE TEXT
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency.
PROHIBITION OF SALE, SUPPLY AND/OR USE
Not applicable.
-
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One ml of solution contains:
Active substance:
Maropitant (as maropitant citrate monohydrate) 10 mg
Excipients:
Metacresol (as preservative) 3.3 mg
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Solution for injection.
A clear, colourless to light yellow solution.
4. CLINICAL PARTICULARS4.1 Target species
Dogs and cats.
-
4.2 Indications for use, specifying the target species
Dogs
- • For the treatment and prevention of nausea induced by chemotherapy.
- • For the prevention of vomiting except that induced by motion sickness.
- • For the treatment of vomiting, in combination with other supportive measures.
- • For the prevention of perioperative nausea and vomiting and improvement in recovery from general anaesthesia after use of the p – opiate receptor agonist morphine.
Cats
- • For the prevention of vomiting and the reduction of nausea, except that induced by motion sickness.
- • For the treatment of vomiting, in combination with other supportive measures.
4.3 Contraindications
None.
-
4.4 Special warnings for each target species
Vomiting can be associated with serious, severely debilitating conditions including gastrointestinal obstructions; therefore, appropriate diagnostic evaluations should be employed.
Good veterinary practice indicates that antiemetics should be used in conjunction with other veterinary and supportive measures such as dietary control and fluid replacement therapy while addressing the underlying causes of the vomiting.
The use of Cerenia solution for injection against vomiting due to motion sickness is not recommended.
Dogs:
Although Cerenia has been demonstrated to be effective in both the treatment and prevention of emesis induced by chemotherapy, it was found more efficacious if used preventively. Therefore, it is recommended to administer the antiemetic prior to administration of the chemotherapeutic agent.
Cats:
The efficacy of Cerenia in reduction of nausea was demonstrated in studies using a model (xylazine-induced nausea).
-
4.5 Special precautions for use
Special precautions for use in animals
The safety of the veterinary medicinal product has not been established in dogs less than 8 weeks of age, or in cats less than 16 weeks of age, and in pregnant or lactating dogs and cats. Use only according to the benefit-risk assessment by the responsible veterinarian.
Maropitant is metabolised in the liver and therefore should be used with caution in patients with hepatic disease. As maropitant is accumulated in the body during a 14-day treatment period due to metabolic saturation, careful monitoring of liver function and any adverse events should be implemented during long term treatment.
Cerenia should be used with caution in animals suffering from or with predisposition for cardiac diseases as maropitant has affinity to Ca- and K-ion channels. Increases of approximately 10% in the QT interval of the ECG were observed in a study on healthy beagle dogs administered 8 mg/kg orally; however, such an increase is unlikely to be of clinical significance.
Due to the frequent occurrence of transient pain during subcutaneous injection, appropriate animal restraining measures may have to be applied. Injecting the product at refrigerated temperature may reduce pain at injection.
Special precautions to be taken by the person administering the veterinary medicinal product to animals
People with known hypersensitivity to maropitant should administer the veterinary medicinal product with caution.
Wash hands after use. In case of accidental self-injection seek medical advice immediately and show the package leaflet or the label to the physician. In laboratory studies, maropitant has been shown to be a potential eye irritant. In the case of accidental eye exposure, flush the eyes with plenty of water and seek medical attention.
-
4.6 Adverse reactions (frequency and seriousness)
Pain at injection site may occur when injected subcutaneously. In cats, moderate to severe response to injection is very commonly observed (in approximately one third of cats).
Anaphylactic type reactions (allergic oedema, urticaria, erythema, collapse, dyspnoea, pale mucous membranes) may occur in very rare cases.
Lethargy has been reported in very rare cases, based on post-marketing safety experience.
The frequency of adverse reactions is defined using the following convention:
-
– very common (more than 1 in 10 animals treated displaying adverse reaction(s))
-
– common (more than 1 but less than 10 animals in 100 animals treated)
-
– uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
-
– rare (more than 1 but less than 10 animals in 10,000 animals treated)
-
– very rare (less than 1 animal in 10,000 animals treated, including isolated reports).
-
4.7 Use during pregnancy, lactation or lay
Use only according to the benefit-risk assessment by the responsible veterinarian, because conclusive reproductive toxicity studies have not been conducted in any animal species.
4.8 Interaction with other medicinal products and other forms of interaction
Cerenia should not be used concomitantly with Ca-channel antagonists as maropitant has affinity to Ca-channels.
Maropitant is highly bound to plasma proteins and may compete with other highly bound medicines.
-
4.9 Amounts to be administered and administration route
For subcutaneous or intravenous use in dogs and cats.
Cerenia solution for injection should be injected subcutaneously or intravenously, once daily, at a dose of 1 mg/kg bodyweight (1 ml/10 kg bodyweight) for up to 5 consecutive days. Intravenous administration of Cerenia should be given as a single bolus without mixing the product with any other fluids.
In dogs, Cerenia can be used to treat or prevent vomiting either as tablets or as solution for injection administered once daily. Cerenia solution for injection may be administered for up to five days and Cerenia tablets for up to fourteen days.
To prevent vomiting, Cerenia solution for injection should be administered more than 1 hour in advance. The effect duration is approximately 24 h and therefore treatment can be given the night before administration of an agent that may cause emesis e.g. chemotherapy.
As the pharmacokinetic variation is large and maropitant accumulates in the body after once daily repeated administration, lower doses than recommended might be sufficient in some individuals and when repeating the dose.
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
Apart from transient reactions at the injection site following subcutaneous administration, Cerenia solution for injection was well tolerated in dogs and young cats injected daily with up to 5 mg/kg (5 times the recommended dose) for 15 consecutive days (3-times the recommended duration of administration). No data have been presented on overdoses in adult cats.
-
4.11 Withdrawal period(s)
Not applicable.
5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: Antiemetics.
ATCvet code: QA04AD90.
Maropitant is a potent and selective neurokinin (NK-1) receptor antagonist, which acts by inhibiting the binding of substance P, a neuropeptide of the tachykinin family, in the CNS.
5.1 Pharmacodynamic properties
Vomiting is a complex process coordinated centrally by the emetic centre. This centre 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 centre and is considered the key neurotransmitter involved in vomiting. By inhibiting the binding of substance P within the emetic centre, maropitant is effective against neural and humoral (central and peripheral) causes of vomiting.
A variety of in vitro assays have demonstrated that maropitant binds selectively at the NK1 receptor with dose-dependent functional antagonism of substance P activity.
Maropitant is effective against vomiting. The anti-emetic efficacy of maropitant against central and peripheral emetics was demonstrated in experimental studies including apomorphine, cisplatin and syrup of ipecac (dogs) and xylazine (cats).
Signs of nausea in dogs including excessive salivation and lethargy might remain after treatment.
-
5.2 Pharmacokinetic particulars
Dogs
The pharmacokinetic profile of maropitant when administered as a single subcutaneous dose of 1 mg/kg body weight to dogs was characterised by a maximum concentration (Cmax) in plasma of approximately 92 ng/ml; this was achieved within 0.75 hours post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t1/2) of 8.84 hours. Following a single intravenous dose at 1 mg/kg the initial plasma concentration was 363 ng/ml. The volume of distribution at steady-state (Vss) was 9.3 l/kg and systemic clearance was 1.5 l/h/kg. The elimination t1/2 following intravenous dosing was approximately 5.8 h.
During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.
The bioavailability of maropitant after subcutaneous administration in dogs was 90.7%. Maropitant displays linear kinetics when administered subcutaneously within the 0.5–2 mg/kg dose range.
Following repeated subcutaneous administration of once-daily doses of 1 mg/kg bodyweight for five consecutive days, accumulation was 146%. Maropitant undergoes cytochrome P450 (CYP) metabolism in the liver. CYP2D15 and CYP3A12 were identified as the canine isoforms involved in the hepatic biotransformation of maropitant.
Renal clearance is a minor route of elimination, with less than 1% of a 1 mg/kg subcutaneous dose appearing in the urine as either maropitant or its major metabolite. Plasma protein binding of maropitant in dogs is more than 99%.
Cats
The pharmacokinetic profile of maropitant when administered as a single subcutaneous dose of 1 mg/kg body weight to cats was characterised 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. Following a single intravenous dose at 1 mg/kg the initial plasma concentration was 1040 ng/ml. The volume of distribution at steady-state (Vss) was 2.3 l/kg and systemic clearance was 0.51 l/h/kg. The elimination t1/2 following intravenous dosing was approximately 4.9 h. There appears to be an age-related effect on the pharmacokinetics of maropitant in cats with kittens having higher clearance than adults.
During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.
The bioavailability of maropitant after subcutaneous administration in cats was 91.3%. 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%. 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.
Renal and faecal clearances are minor routes of elimination for maropitant, with less than 1% of a
1 mg/kg subcutaneous dose appearing in the urine or faeces as maropitant. For the major metabolite 10.4% of the maropitant dose was recovered in urine and 9.3% in faeces. Plasma protein binding of maropitant in cats was estimated to be 99.1%.
6. PHARMACEUTICAL PARTICULARS6.1 List of excipients
Sulphobutyl ether P—cyclodextrin (SBECD)
Metacresol
Water for injections
6.2 Major incompatibilities
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products in the same syringe.
6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 3 years.
Shelf life after first opening the immediate packaging: 60 days.
6.4 Special precautions for storage
This veterinary medicinal product does not require any special storage conditions.
-
6.5 Nature and composition of immediate packaging
Amber molded glass type 1 vial, 20 ml, chlorobutyl rubber stopper and aluminium overseal with flip-off button.
Each cardboard box contains 1 vial.
-
6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products
7. MARKETING AUTHORISATION HOLDER
Zoetis Belgium SA
Rue Laid Burniat 1
1348 Louvain-la-Neuve
BELGIUM
8. MARKETING AUTHORISATION NUMBER(S)
EU/2/06/062/005
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 29/09/2006.
Date of last renewal: 29/09/2011.