Arocenia 10 mg/ml solution for injection for dogs and cats

Solution for injection. Clear, colourless to light yellow or to slightly brown solution.

Each ml contains active substance 10 mg of maropitant as maropitant citrate monohydrate

- 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 μ-opiate receptor agonist morphine.

- 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.

The veterinary medicinal product 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 the veterinary medicinal product should be given as a single bolus without mixing the veterinary medicinal product with any other fluids.

To prevent vomiting, the veterinary medicinal product 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.

For administration by subcutaneous injection, see also “Special precautions for use in animals:” (section 4.5 of SPC).

The cap may be safely punctured up to 40 times. It is recommended that a draw-off needle be used to reduce the number of times the septum is punctured.

Use only according to the benefit-risk assessment by the responsible veterinarian

Conclusive reproductive toxicity studies have not been conducted in any animal 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.

Dogs: Although maropitant 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 maropitant in reduction of nausea was demonstrated in studies using a model (xylazine induced nausea).

The veterinary medicinal product 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.

Use only according to the benefit-risk assessment by the responsible veterinarian

Conclusive reproductive toxicity studies have not been conducted in any animal 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.

Dogs: Although maropitant 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 maropitant in reduction of nausea was demonstrated in studies using a model (xylazine induced nausea).

Injection site pain.1,2

Anaphylactic-type reaction (allergic oedema, urticaria, erythema, collapse, dyspnoea, pale mucous membrane).

Lethargy.

Neurological disorders (ataxia, convulsion/seizure or muscle tremor).

1When injected subcutaneously to cat: moderate to severe response to injection (in approximately one third of cats).

2When injected subcutaneously to dog.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See the package leaflet for contact details.

Apart from transient reactions at the injection site following subcutaneous administration, maropitant 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.

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

i) 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.

The veterinary medicinal product 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 veterinary medicinal product at refrigerated temperature may reduce pain at injection.

ii) Special precautions to be taken by the person administering the veterinary medicinal product to animals:

Maropitant is a neurokinin-1 (NK1) receptor antagonist that acts in the central nervous system. The veterinary medicinal product may therefore cause nausea, dizziness and drowsiness in case of accidental self-injection. If accidental self-injection occurs, seek medical advice immediately and show the package leaflet or the label to the physician.

Due to the content of benzyl alcohol the veterinary medicinal product may cause mild local irritation. Skin contact should therefore be avoided. In case of accidental exposure, wash affected skin area with plenty of water.

The veterinary medicinal product may cause skin sensitisation. People with known hypersensitivity to maropitant or to any of the excipients should administer the veterinary medicinal product with caution. If you develop symptoms such as a skin rash after accidental exposure, seek medical advice and show the physician this warning.

The veterinary medicinal product may cause eye irritation. Eye contact should be avoided. In case of accidental eye exposure, flush the eyes with plenty of water and seek medical attention.

Wash hands after use.

Shelf life of the veterinary medicinal product as packaged for sale: 3 years.

Shelf life after first opening the immediate packaging: 60 days.

This veterinary medicinal product does not require any special storage conditions.

Medicines should not be disposed of via wastewater.

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

Cardboard box containing 1 vial of 20 ml.

Amber glass vial type I with bromobutyl rubber stopper and aluminium overseal with flip-off tab.

KRKA, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

Benzyl alcohol E1519

Sulfobutylbetadex sodium

Water for injections

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%.

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%.

Vm 01656/5038