Cepedex

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  • Cepedex
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  • Fáanlegt í:
  • Cepedex
    Evrópusambandið
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  • enska

Meðferðarupplýsingar

  • Meðferðarhópur:
  • Cats, Dogs
  • Lækningarsvæði:
  • PSYCHOLEPTICS, HYPNOTICS AND SEDATIVES
  • Ábendingar:
  • Non-invasive, mildly to moderately painful, procedures and examinations which require restraint, sedation and analgesia in dogs and cats. Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor surgical procedures. Premedication in dogs and cats before induction and maintenance of general anaesthesia.,
  • Vörulýsing:
  • Revision: 2

Staða

  • Heimild:
  • EMA - European Medicines Agency
  • Leyfisstaða:
  • Authorised
  • Leyfisnúmer:
  • EMEA/V/C/004376
  • Leyfisdagur:
  • 12-12-2016
  • EMEA númer:
  • EMEA/V/C/004376
  • Síðasta uppfærsla:
  • 27-03-2019

Opinber matsskýrsla

EMA/664746/2016

EMEA/V/C/004376

EPAR summary for the public

Cepedex

dexmedetomidine

This is a summary of the European public assessment report (EPAR) for Cepedex. It explains how the

Agency assessed this veterinary medicine to recommend its authorisation in the European Union (EU)

and its conditions of use. It is not intended to provide practical advice on how to use Cepedex.

For practical information about using Cepedex, animal owners or keepers should read the package

leaflet or contact their veterinarian or pharmacist.

What is Cepedex and what is it used for?

Cepedex is a medicine used to sedate (calm down) dogs and cats in the following situations:

when carrying out mildly to moderately painful procedures and examinations that require the animal

to be restrained or sedated and made less sensitive to pain (analgesia). Cepedex is used in

non-invasive procedures which do not involve breaking the skin or a body cavity.

as premedication before inducing general anaesthesia.

Cepedex can also be used in dogs to provide pain relief and deep sedation when carrying out medical

procedures and minor surgery where it is used in combination with butorphanol (a sedative and

analgesic).

Cepedex contains the active substance dexmedetomidine and is a ‘generic medicine’. This means that

Cepedex is similar to a ‘reference medicine’ already authorised in the EU called Dexdomitor.

For further information, see the package leaflet.

How is Cepedex used?

Cepedex is available as a solution for injection and can only be obtained with a prescription.

In dogs, Cepedex is given by injection into a vein or a muscle. In cats, it is given by injection into a

muscle. For dogs the dose depends on their body surface area (calculated using bodyweight) and in cats

it is based on bodyweight. It also depends on the use and the way it is given. The duration and depth of

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sedation and analgesia depend on the dose that is used.

How does Cepedex work?

Cepedex is an alpha2-adrenoceptor agonist. It works by attaching to receptors known as

alpha2-adrenergic receptors and preventing the release of the neurotransmitter noradrenaline from

nerve cells in the body. A neurotransmitter is a substance that nerve cells use to communicate with

neighbouring cells. Since noradrenaline is involved in maintaining alertness and arousal, reducing its

release decreases the level of consciousness, including the sensation of pain. Dexmedetomidine is

closely related to another substance used to sedate animals, medetomidine, that has been used in

veterinary medicine for many years.

How has Cepedex been studied?

The company provided information on the quality and manufacture of Cepedex. No additional studies

were needed as Cepedex is a generic medicine that is given by injection, is similar in composition to, and

contains the same active substance as the reference medicine, Dexdomitor.

What are the benefits and risks of Cepedex?

Because Cepedex is a generic medicine and is bioequivalent to the reference medicine, its benefits and

risks are taken as being the same as the reference medicine’s.

What are the precautions for the person who gives the medicine or comes

into contact with the animal?

Safety information has been included in the summary of product characteristics and the package leaflet

for Cepedex, including the appropriate precautions to be followed by healthcare professionals and

animal owners or keepers when giving Cepedex. Because Cepedex is a generic medicine and is

bioequivalent to the reference medicine the precautions are the same as for the reference medicine.

Why is Cepedex approved?

The Agency’s Committee for Medicinal Products for Veterinary Use (CVMP) concluded that, in

accordance with EU requirements, Cepedex has been shown to have comparable quality to Dexdomitor.

Therefore, the CVMP’s view was that, as for Dexdomitor, the benefits outweigh the identified risks. The

Committee recommended that Cepedex be approved for use in the EU.

Other information about Cepedex?

The European Commission granted a marketing authorisation valid throughout the EU for Cepedex on

13 December 2016.

The full EPAR for Cepedex can be found on the Agency’s website: ema.europa.eu/Find

medicine/Veterinary medicines/European public assessment reports. For more information about

treatment with Cepedex, animal owners or keepers should read the package leaflet or contact their

veterinarian or pharmacist.

The full EPAR for the reference medicine can also be found on the Agency’s website.

This summary was last updated in October 2016.

Cepedex

EMA/664746/2016

Page 2/2

Upplýsingar um fylgiseðil sjúklinga: samsetning, vísbendingar, aukaverkanir, skammtar, milliverkanir, aukaverkanir, meðgöngu, brjóstagjöf

B. PACKAGE LEAFLET

PACKAGE LEAFLET

Cepedex 0.1 mg/ml solution for injection for dogs and cats

1.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF

THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH

RELEASE, IF DIFFERENT

Marketing authorisation holder and manufacturer responsible for batch release:

CP-Pharma Handelsgesellschaft mbH

Ostlandring 13, 31303 Burgdorf

Germany

2.

NAME OF THE VETERINARY MEDICINAL PRODUCT

Cepedex 0.1 mg/ml solution for injection for dogs and cats

dexmedetomidine hydrochloride

3.

STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

1 ml contains:

Active substance:

Dexmedetomidine hydrochloride

0.1 mg

(equivalent to dexmedetomidine

0.08 mg)

Excipients:

Methyl parahydroxybenzoate (E 218)

2.0 mg

Propyl parahydroxybenzoate

0.2 mg

Clear, colourless solution for injection.

4.

INDICATION(S)

Non-invasive, mildly to moderately painful, procedures and examinations which require restraint,

sedation and analgesia in dogs and cats.

Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor

surgical procedures.

Premedication in dogs and cats before induction and maintenance of general anaesthesia.

5.

CONTRAINDICATIONS

Do not use in animals with cardiovascular disorders.

Do not use in animals with severe systemic disease or in animals that are moribund.

Do not use in case of known hypersensitivity to the active substance or to any of the excipients.

6.

ADVERSE REACTIONS

By virtue of its α2-adrenergic activity, dexmedetomidine causes a decrease in heart rate and body

temperature.

In some dogs and cats, a decrease in respiratory rate may occur. Rare instances of pulmonary oedema

have been reported. Blood pressure will increase initially and then return to normal or below normal.

Due to peripheral vasoconstriction and venous desaturation in the presence of normal arterial

oxygenation, the mucous membranes may appear pale and/or with a blue tinge.

Vomiting may occur 5-10 minutes after injection. Some dogs and cats may also vomit at the time of

recovery.

Muscle tremors may occur during sedation.

Corneal opacities may occur during sedation (see also the section on Special precautions for the use in

animals).

When dexmedetomidine and ketamine are used sequentially, with a 10 minute interval, cats may

occasionally experience AV-block or extrasystole. Expected respiratory events are bradypnoea,

intermittent respiratory patterns, hypoventilation, and apnoea. In clinical trials the incidence of

hypoxaemia was common, especially within the 15 first minutes into dexmedetomidine-ketamine

anaesthesia. Vomiting, hypothermia and nervousness have been reported after such use.

When dexmedetomidine and butorphanol are used concomitantly in dogs, bradypnoea, tachypnoea, an

irregular respiratory pattern (20-30 sec apnoea followed by several rapid breaths), hypoxaemia,

muscle twitch or tremor or paddling, excitation, hypersalivation, retching, vomiting, urination, skin

erythema, a sudden arousal, or prolonged sedation may occur. Brady- and tachyarrhythmias have been

reported. These may include profound sinus bradycardia, 1

and 2

degree AV block, sinus arrest or

pause, as well as atrial, supraventricular and ventricular premature complexes.

When dexmedetomidine is used as a premedicant in dogs bradypnoea, tachypnoea and vomiting may

occur. Brady- and tachyarrhythmias have been reported and include profound sinus bradycardia, 1

and 2

degree AV block and sinus arrest. Supraventricular and ventricular premature complexes,

sinus pause and 3

degree AV block may be observed in rare cases.

When dexmedetomidine is used as a premedicant in cats, vomiting, retching, pale mucous membranes,

and low body temperature may occur. Intramuscular dosing at 40 micrograms/kg (followed by

ketamine or propofol) frequently resulted in sinus bradycardia and sinus arrhythmia, occasionally

resulted in 1

degree atrioventricular block, and rarely resulted in supraventricular premature

depolarizations, atrial bigeminy, sinus pauses, 2

degree atrioventricular block, or escape

beats/rhythms.

If you notice any serious effects or other effects not mentioned in this package leaflet, please inform

your veterinary surgeon.

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).

7.

TARGET SPECIES

Dogs and cats.

8.

DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

The veterinary medicinal product is intended for:

- Dogs: intravenous or intramuscular use

- Cats: intramuscular use

The veterinary medicinal product is not intended for repeat injections.

Dexmedetomidine, butorphanol and/or ketamine can be mixed in the same syringe as they have been

shown to be pharmaceutically compatible.

The following doses are recommended:

Dogs:

Dexmedetomidine doses are based on body surface area:

For non-invasive, mildly to moderately painful procedures and examinations requiring restraint,

sedation and analgesia:

Intravenously: up to 375 micrograms/square metre body surface area.

Intramuscularly: up to 500 micrograms/square metre body surface area.

When administering in conjunction with butorphanol (0.1 mg/kg) for deep sedation and analgesia, the

intramuscular dose of dexmedetomidine is 300 micrograms/square metre body surface area.

The premedication dose of dexmedetomidine is 125 – 375 micrograms/square metre body surface

area, administered 20 minutes prior to induction for procedures requiring anaesthesia. The dose

should be adjusted to the type of surgery, length of procedure and patient temperament.

Concomitant use of dexmedetomidine and butorphanol produces sedative and analgesic effects

beginning no later than 15 minutes after administration. The peak sedative and analgesic effects are

reached within 30 minutes after administration. Sedation lasts for at least 120 minutes post

administration and analgesia lasts for at least 90 minutes. Spontaneous recovery occurs within 3

hours.

Premedication with dexmedetomidine will significantly reduce the dose of the induction agent

required and will reduce volatile anaesthetic requirements for maintenance anaesthesia. In a clinical

study, the requirement for propofol and thiopental was reduced by 30% and 60% respectively. All

anaesthetic agents used for induction or maintenance of anaesthesia should be administered to effect.

In a clinical study, dexmedetomidine contributed to postoperative analgesia for 0.5 – 4 hours.

However this duration is dependent on a number of variables and further analgesia should be

administered in accordance with clinical judgement.

The corresponding doses based on body weight are presented in the following tables. Use of an

appropriately graduated syringe is recommended to ensure accurate dosing when administering small

volumes.

*only intramuscularly

For higher weight ranges, use Cepedex 0.5 mg/ml and its dosing tables.

Cats:

The dose for cats is 40 micrograms dexmedetomidine hydrochloride/kg bw equal to a dose volume of

0.4 ml Cepedex/kg bw when used for non-invasive, mildly to moderately painful procedures requiring

restraint, sedation and analgesia.

When dexmedetomidine is used for premedication in cats, the same dose is used. Premedication with

dexmedetomidine will significantly reduce the dose of the induction agent required and will reduce

volatile anaesthetic requirements for maintenance anaesthesia. In a clinical study, the requirement for

propofol was reduced by 50%. All anaesthetic agents used for induction or maintenance of

anaesthesia should be administered to effect.

Anaesthesia can be induced 10 minutes after premedication by intramuscular administration of a

target dose of 5 mg ketamine/ kg bw or by intravenous administration of propofol to effect. Dosing for

cats is presented in the following table.

Cat

Weight

Dexmedetomidine 40 micrograms/kg intramuscularly

(kg)

(mcg/kg)

(ml)

2.1-3

For higher weight ranges, use Cepedex 0.5 mg/ml and its dosing table.

9.

ADVICE ON CORRECT ADMINISTRATION

Dog

Weight

Dexmedetomidine

125 micrograms/m

2

Dexmedetomidine

375 micrograms/m

2

Dexmedetomidine

500 micrograms/m

2*

(kg)

(mcg/kg)

(ml)

(mcg/kg)

(ml)

(mcg/kg)

(ml)

28.1

0.75

3.1-4

0.25

0.85

4.1-5

0.35

5.1-10

19.6

1.45

10.1-13

0.65

16.8

13.1-15

0.75

15.1-20

0.85

For deep sedation and analgesia with butorphanol

Dog

Weight

Dexmedetomidine

300 micrograms/m

2

intramuscularly

(kg)

(mcg/kg)

(ml)

3.1-4

4.1-5

22.2

5.1-10

16.7

1.25

10.1-13

13.1-15

12.5

1.75

The expected sedative and analgesic effects are reached within 15 minutes after administration and

are maintained up to 60 minutes after administration. Sedation may be reversed with atipamezole (see

section 12

overdose

). Atipamezole should not be administered prior to 30 minutes following ketamine

administration.

10.

WITHDRAWAL PERIOD(S)

Not applicable.

11.

SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

Shelf-life after first opening the immediate packaging: 56 days.

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

Do not use this veterinary medicinal product after the expiry date which is stated on the package after

EXP.

The expiry date refers to the last day of that month.

12.

SPECIAL WARNINGS

Special warnings

The administration of dexmedetomidine to puppies younger than 16 weeks and kittens younger than

12 weeks has not been studied.

Special precautions for use in animals

Treated animals should be kept warm and at a constant temperature, both during the procedure and

recovery.

It is recommended that animals are fasted for 12 hours prior to Cepedex administration. Water may be

given.

After treatment, the animal should not be given water or food before it is able to swallow.

Corneal opacities may occur during sedation. The eyes should be protected by a suitable eye lubricant.

To be used with precaution in elderly animals.

The safety of dexmedetomidine has not been established in males intended for breeding.

Nervous, aggressive or excited animals should be given the possibility to calm down before initiation

of treatment.

Frequent and regular monitoring of respiratory and cardiac function should be performed. Pulse

oximetry may be useful but is not essential for adequate monitoring. Equipment for manual ventilation

should be available in case of respiratory depression or apnoea when dexmedetomidine and ketamine

are used sequentially to induce anaesthesia in cats. It is also advisable to have oxygen readily

available, should hypoxaemia be detected or suspected.

Sick and debilitated dogs and cats should only be premedicated with dexmedetomidine before

induction and maintenance of general anaesthesia based on a risk-benefit assessment.

Use of dexmedetomidine as a premedicant in dogs and cats significantly reduces the amount of

induction medicinal product required for induction of anaesthesia. Attention should be given during

the administration of intravenous induction medicinal products to effect. Volatile anaesthetic

requirements for maintenance anaesthesia are also reduced.

Special precautions to be taken by the person administering the veterinary medicinal product to

animals

Dexmedetomidine is a sedative and sleep inducing drug. Care should be taken to avoid self-injection.

In case of accidental oral intake or self-injection, seek medical advice immediately and show the

package insert to the physician but DO NOT DRIVE as sedation and changes in blood pressure may

occur. Pregnant women should administer the product with special caution to avoid self-injection

since uterine contractions and decreased foetal blood pressure may occur after accidental systemic

exposure.

Avoid skin, eye or mucosal contact; the use of impermeable gloves is advisable. In case of skin or

mucosal contact, wash the exposed skin immediately after exposure with large amounts of water and

remove contaminated clothes that are in direct contact with skin. In case of eye contact, rinse

abundantly with fresh water. If symptoms occur, seek the advice of a physician.

People with known hypersensitivity to the active substance or any of the excipients should administer

the veterinary medicinal product with caution.

Advice to physicians: Cepedex is an α2-adrenoreceptor agonist, symptoms after absorption may

involve clinical effects including dose-dependent sedation, respiratory depression, bradycardia,

hypotension, a dry mouth, and hyperglycaemia. Ventricular arrhythmias have also been reported.

Respiratory and haemodynamic symptoms should be treated symptomatically. The specific

α2-adrenoceptor antagonist, atipamezole, which is approved for use in animals, has been used in

humans only experimentally to antagonize dexmedetomidine-induced effects.

Use during pregnancy and lactation

The safety of dexmedetomidine has not been established during pregnancy and lactation in the target

species. Therefore the use of the product during pregnancy and lactation is not recommended.

Interactions with other medicinal products and other forms of interaction

The use of other central nervous system depressants is expected to potentiate the effects of

dexmedetomidine and therefore an appropriate dose adjustment should be made. Anticholinergics

should be used with caution with dexmedetomidine.

Administration of atipamezole after dexmedetomidine rapidly reverses the effects and thus shortens

the recovery period. Within 15 minutes dogs and cats are normally awake and standing.

Cats: After administration of 40 micrograms dexmedetomidine/kg bw intramuscularly concurrently

with 5 mg ketamine/kg bw to cats, the maximum concentration of dexmedetomidine increased twofold

but there was no effect on T

. The mean half-life of elimination of dexmedetomidine increased to

1.6 h and the total exposure (AUC) increased by 50%.

A dose of 10 mg ketamine/ kg used concurrently with 40 micrograms dexmedetomidine/ kg may cause

tachycardia.

Atipamezole does not reverse the effect of ketamine.

Overdose (symptoms, emergency procedures, antidotes)

Dogs:

In cases of overdose, or if the effects of dexmedetomidine become potentially life- threatening, the

appropriate dose of atipamezole is 10 times the initial dose of dexmedetomidine (micrograms/ kg bw

or micrograms/ square meter body surface area). The dose volume of atipamezole at the concentration

of 5 mg/ml is one fifth (1/5) of the dose volume of Cepedex 0.1 mg/ml that was given to the dog,

regardless of route of administration of Cepedex.

Cats:

In cases of overdose, or if the effects of dexmedetomidine become potentially life-threatening, the

appropriate antagonist is atipamezole, administered by intramuscular injection, at the following dose:

5 times the initial dose dexmedetomidine in micrograms/kg bw. The dose volume of atipamezole at

the concentration of 5 mg/ml is one-tenth (1/10) the volume of Cepedex 0.1 mg/ml that was given to

the cat.

After concurrent exposure to an overdose of dexmedetomidine (3 times the recommended dose) and

15 mg ketamine/ kg, atipamezole can be administered at the recommended dose level for reversal of

effects induced by dexmedetomidine.

Incompatibilities

None known.

Dexmedetomidine is compatible with butorphanol and ketamine in the same syringe at least for two

hours.

13.

SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED VETERINARY

MEDICINAL PRODUCTS OR WASTE MATERIALS, IF ANY

Ask your veterinary surgeon or pharmacist how to dispose of medicines no longer required. These

measures should help to protect the environment.

14.

DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

15.

OTHER INFORMATION

Colourless Type I glass vials of 5 ml and 10 ml closed with a coated bromobutyl rubber stopper and

aluminium cap in a carton box.

Cardboard box pack sizes:

1 vial of 5 ml

1 or 5 vials of 10 ml

Not all pack sizes may be marketed.

PACKAGE LEAFLET

Cepedex 0.5 mg/ml solution for injection for dogs and cats

1.

NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF

THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH

RELEASE, IF DIFFERENT

Marketing authorisation holder and manufacturer responsible for batch release:

CP Pharma Handelsgesellschaft mbH

Ostlandring 13, 31303 Burgdorf

Germany

2.

NAME OF THE VETERINARY MEDICINAL PRODUCT

Cepedex 0.5 mg/ml solution for injection for dogs and cats

dexmedetomidine hydrochloride

3.

STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

1 ml contains:

Active substance:

Dexmedetomidine hydrochloride

0.5 mg

(equivalent to dexmedetomidine

0.42 mg)

Excipient(s):

Methyl parahydroxybenzoate (E 218)

1.6 mg

Propyl parahydroxybenzoate

0.2 mg

Clear, colourless solution for injection.

4.

INDICATION(S)

Non-invasive, mildly to moderately painful, procedures and examinations which require restraint,

sedation and analgesia in dogs and cats.

Deep sedation and analgesia in dogs in concomitant use with butorphanol for medical and minor

surgical procedures.

Premedication in dogs and cats before induction and maintenance of general anaesthesia.

5.

CONTRAINDICATIONS

Do not use in animals with cardiovascular disorders.

Do not use in animals with severe systemic disease or in animals that are moribund.

Do not use in case of known hypersensitivity to the active substance or to any of the excipients.

6.

ADVERSE REACTIONS

By virtue of its α2-adrenergic activity, dexmedetomidine causes a decrease in heart rate and body

temperature.

In some dogs and cats, a decrease in respiratory rate may occur. Rare instances of pulmonary oedema

have been reported. Blood pressure will increase initially and then return to normal or below normal.

Due to peripheral vasoconstriction and venous desaturation in the presence of normal arterial

oxygenation, the mucous membranes may appear pale and/or with a blue tinge.

Vomiting may occur 5-10 minutes after injection. Some dogs and cats may also vomit at the time of

recovery.

Muscle tremors may occur during sedation.

Corneal opacities may occur during sedation (see also the section on Special precautions for the use in

animals).

When dexmedetomidine and ketamine are used sequentially, with a 10 minute interval, cats may

occasionally experience AV-block or extrasystole. Expected respiratory events are bradypnoea,

intermittent respiratory patterns, hypoventilation, and apnoea. In clinical trials the incidence of

hypoxaemia was common, especially within the 15 first minutes into dexmedetomidine-ketamine

anaesthesia. Vomiting, hypothermia and nervousness have been reported after such use.

When dexmedetomidine and butorphanol are used concomitantly in dogs, bradypnoea, tachypnoea, an

irregular respiratory pattern (20-30 sec apnoea followed by several rapid breaths), hypoxaemia,

muscle twitch or tremor or paddling, excitation, hypersalivation, retching, vomiting, urination, skin

erythema, a sudden arousal, or prolonged sedation may occur. Brady- and tachyarrhythmias have been

reported. These may include profound sinus bradycardia, 1

and 2

degree AV block, sinus arrest or

pause, as well as atrial, supraventricular and ventricular premature complexes.

When dexmedetomidine is used as a premedicant in dogs bradypnoea, tachypnoea and vomiting may

occur. Brady- and tachyarrhythmias have been reported and include profound sinus bradycardia, 1

and 2

degree AV block and sinus arrest. Supraventricular and ventricular premature complexes,

sinus pause and 3

degree AV block may be observed in rare cases.

When dexmedetomidine is used as a premedicant in cats, vomiting, retching, pale mucous membranes,

and low body temperature may occur. Intramuscular dosing at 40 micrograms/kg (followed by

ketamine or propofol) frequently resulted in sinus bradycardia and sinus arrhythmia, occasionally

resulted in 1

degree atrioventricular block, and rarely resulted in supraventricular premature

depolarizations, atrial bigeminy, sinus pauses, 2

degree atrioventricular block, or escape

beats/rhythms.

If you notice any serious effects or other effects not mentioned in this package leaflet,

please inform your veterinary surgeon.

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).

7.

TARGET SPECIES

Dogs and cats.

8.

DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION

The veterinary medicinal product is intended for:

- Dogs: intravenous or intramuscular use

- Cats: intramuscular use

The veterinary medicinal product is not intended for repeat injections.

Dexmedetomidine, butorphanol and/or ketamine can be mixed in the same syringe as they have been

shown to be pharmaceutically compatible.

The following doses are recommended:

Dogs:

Dexmedetomidine doses are based on body surface area:

For non-invasive, mildly to moderately painful procedures and examinations requiring restraint,

sedation and analgesia:

Intravenously: up to 375 micrograms/square metre body surface area.

Intramuscularly: up to 500 micrograms/square metre body surface area

When administering in conjunction with butorphanol (0.1 mg/kg) for deep sedation and analgesia, the

intramuscular dose of dexmedetomidine is 300 micrograms/square metre body surface area.

The premedication dose of dexmedetomidine is 125 – 375 micrograms/square metre body surface

area, administered 20 minutes prior to induction for procedures requiring anaesthesia. The dose

should be adjusted to the type of surgery, length of procedure and patient temperament.

Concomitant use of dexmedetomidine and butorphanol produces sedative and analgesic effects

beginning no later than 15 minutes after administration. The peak sedative and analgesic effects are

reached within 30 minutes after administration. Sedation lasts for at least 120 minutes post

administration and analgesia lasts for at least 90 minutes. Spontaneous recovery occurs within 3

hours.

Premedication with dexmedetomidine will significantly reduce the dosage of the induction agent

required and will reduce volatile anaesthetic requirements for maintenance anaesthesia. In a clinical

study, the requirement for propofol and thiopental was reduced by 30% and 60% respectively. All

anaesthetic agents used for induction or maintenance of anaesthesia should be administered to effect.

In a clinical study, dexmedetomidine contributed to postoperative analgesia for 0.5 – 4 hours.

However this duration is dependent on a number of variables and further analgesia should be

administered in accordance with clinical judgement.

The corresponding doses based on body weight are presented in the following tables. Use of an

appropriately graduated syringe is recommended to ensure accurate dosing when administering small

volumes.

Dog

Weight

Dexmedetomidine

125 micrograms/m

2

Dexmedetomidine

375 micrograms/m

2

Dexmedetomidine

500 micrograms/m

2*

(kg)

(mcg/kg)

(ml)

(mcg/kg)

(ml)

(mcg/kg)

(ml)

0.04

28.1

0.12

0.15

3.1-4

0.05

0.17

4.1-5

0.07

5.1-10

19.6

0.29

10.1-13

0.13

16.8

0.38

13.1-15

0.15

15.7

0.44

15.1-20

0.17

14.6

0.51

20.1-25

13.4

25.1-30

0.23

12.6

0.69

30.1-33

0.25

0.75

33.1-37

0.27

11.6

0.81

37.1-45

14.5

45.1-50

0.33

10.5

0.99

50.1-55

0.35

10.1

1.06

13.5

55.1-60

0.38

1.13

60.1-65

1.19

12.8

65.1-70

0.42

1.26

12.5

70.1-80

0.45

1.35

12.3

>80

0.47

1.42

*only intramuscularly

For deep sedation and analgesia with butorphanol

Dog

Weight

Dexmedetomidine

300 micrograms/m

2

intramuscularly

(kg)

(mcg/kg)

(ml)

0.12

3.1-4

0.16

4.1-5

22.2

5.1-10

16.7

0.25

10.1-13

13.1-15

12.5

0.35

15.1-20

11.4

20.1-25

11.1

25.1-30

0.55

30.1-33

33.1-37

0.65

37.1-45

45.1-50

50.1-55

0.85

55.1-60

60.1-65

0.95

65.1-70

70.1-80

>80

Cats:

The dose for cats is 40 micrograms dexmedetomidine hydrochloride/kg bw equal to a dose volume of

0.08 ml Cepedex/kg bw when used for non-invasive, mildly to moderately painful procedures

requiring restraint, sedation and analgesia.

When dexmedetomidine is used for premedication in cats, the same dose is used. Premedication with

dexmedetomidine will significantly reduce the dose of the induction agent required and will reduce

volatile anaesthetic requirements for maintenance anaesthesia. In a clinical study, the requirement for

propofol was reduced by 50%. All anaesthetic agents used for induction or maintenance of

anaesthesia should be administered to effect.

Anaesthesia can be induced 10 minutes after premedication by intramuscular administration of a

target dose of 5 mg ketamine/ kg bw or by intravenous administration of propofol to effect. Dosing for

cats is presented in the following table.

Cat

Weight

Dexmedetomidine 40 micrograms/kg intramuscularly

(kg)

(mcg/kg)

(ml)

2.1-3

3.1-4

4.1-6

6.1-7

7.1-8

8.1-10

9.

ADVICE ON CORRECT ADMINISTRATION

The expected sedative and analgesic effects are reached within 15 minutes after administration and

are maintained up to 60 minutes after administration. Sedation may be reversed with atipamezole (see

section 12 on

overdose

). Atipamezole should not be administered prior to 30 minutes following

ketamine administration.

The stopper may be safely punctured up to 100 times.

10.

WITHDRAWAL PERIOD(S)

Not applicable.

11.

SPECIAL STORAGE PRECAUTIONS

Keep out of the sight and reach of children.

Shelf-life after first opening the immediate packaging: 56 days.

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

Do not use this veterinary medicinal product after the expiry date which is stated on the package after

EXP.

The expiry date refers to the last day of that month.

12.

SPECIAL WARNINGS

Special warnings

The administration of dexmedetomidine to puppies younger than 16 weeks and kittens younger than

12 weeks has not been studied.

Special precautions for use in animals

Treated animals should be kept warm and at a constant temperature, both during the procedure and

recovery.

It is recommended that animals are fasted for 12 hours prior to Cepedex administration. Water may be

given.

After treatment, the animal should not be given water or food before it is able to swallow.

Corneal opacities may occur during sedation. The eyes should be protected by a suitable eye lubricant.

To be used with precaution in elderly animals.

The safety of dexmedetomidine has not been established in males intended for breeding.

Nervous, aggressive or excited animals should be given the possibility to calm down before initiation

of treatment.

Frequent and regular monitoring of respiratory and cardiac function should be performed. Pulse

oximetry may be useful but is not essential for adequate monitoring. Equipment for manual ventilation

should be available in case of respiratory depression or apnoea when dexmedetomidine and ketamine

are used sequentially to induce anaesthesia in cats. It is also advisable to have oxygen readily

available, should hypoxaemia be detected or suspected.

Sick and debilitated dogs and cats should only be premedicated with dexmedetomidine before

induction and maintenance of general anaesthesia based on a risk-benefit assessment.

Use of dexmedetomidine as a premedicant in dogs and cats significantly reduces the amount of

induction medicinal product required for induction of anaesthesia. Attention should be given during

the administration of intravenous induction medicinal products to effect. Volatile anaesthetic

requirements for maintenance anaesthesia are also reduced.

Special precautions to be taken by the person administering the veterinary medicinal product to

animals

Dexmedetomidine is a sedative and sleep inducing drug. Care should be taken to avoid self-injection.

In case of accidental oral intake or self-injection, seek medical advice immediately and show the

package insert to the physician but DO NOT DRIVE as sedation and changes in blood pressure may

occur.

Pregnant women should administer the product with special caution to avoid self-injection since

uterine contractions and decreased foetal blood pressure may occur after accidental systemic

exposure.

Avoid skin, eye or mucosal contact; the use of impermeable gloves is advisable. In case of skin or

mucosal contact, wash the exposed skin immediately after exposure with large amounts of water and

remove contaminated clothes that are in direct contact with skin. In case of eye contact, rinse

abundantly with fresh water. If symptoms occur, seek the advice of a physician.

People with known hypersensitivity to the active substance or any of the excipients should administer

the product with caution.

Advice to physicians: Cepedex is an α2-adrenoreceptor agonist, symptoms after absorption may

involve clinical effects including dose-dependent sedation, respiratory depression, bradycardia,

hypotension, a dry mouth, and hyperglycaemia. Ventricular arrhythmias have also been reported.

Respiratory and haemodynamic symptoms should be treated symptomatically. The specific

α2-adrenoceptor antagonist, atipamezole, which is approved for use in animals, has been used in

humans only experimentally to antagonize dexmedetomidine-induced effects.

Use during pregnancy and lactation

The safety of dexmedetomidine has not been established during pregnancy and lactation in the target

species. Therefore the use of the product during pregnancy and lactation is not recommended.

Interactions with other medicinal products and other forms of interaction

The use of other central nervous system depressants is expected to potentiate the effects of

dexmedetomidine and therefore an appropriate dose adjustment should be made. Anticholinergics

should be used with caution with dexmedetomidine.

Administration of atipamezole after dexmedetomidine rapidly reverses the effects and thus shortens

the recovery period. Within 15 minutes dogs and cats are normally awake and standing.

Cats: After administration of 40 micrograms dexmedetomidine/kg bw intramuscularly concurrently

with 5 mg ketamine/kg bw to cats, the maximum concentration of dexmedetomidine increased twofold

but there was no effect on T

. The mean half-life of elimination of dexmedetomidine increased to

1.6 h and the total exposure (AUC) increased by 50%.

A dose of 10 mg ketamine/ kg used concurrently with 40 micrograms dexmedetomidine/ kg may cause

tachycardia.

Atipamezole does not reverse the effect of ketamine.

Overdose (symptoms, emergency procedures, antidotes)

Dogs:

In cases of overdose, or if the effects of dexmedetomidine become potentially life- threatening, the

appropriate dose of atipamezole is 10 times the initial dose of dexmedetomidine (micrograms/ kg bw

or micrograms/ square meter body surface area). The dose volume of atipamezole at the concentration

of 5 mg/ml equals the dose volume of Cepedex 0.5 mg/ml that was given to the dog, regardless of

route of administration of Cepedex.

Cats:

In cases of overdose, or if the effects of dexmedetomidine become potentially life-threatening, the

appropriate antagonist is atipamezole, administered by intramuscular injection, at the following dose:

5 times the initial dose dexmedetomidine in micrograms/kg bw. The dose volume of atipamezole at

the concentration of 5 mg/ml is one-half (1/2) the volume of Cepedex 0.5 mg/ml that was given to the

cat.

After concurrent exposure to an overdose of dexmedetomidine (3 times the recommended dose) and

15 mg ketamine/ kg, atipamezole can be administered at the recommended dose level for reversal of

effects induced by dexmedetomidine.

Incompatibilities

None known.

Dexmedetomidine is compatible with butorphanol and ketamine in the same syringe at least for two

hours.

13.

SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED VETERINARY

MEDICINAL PRODUCTS OR WASTE MATERIALS, IF ANY

Ask your veterinary surgeon or pharmacist how to dispose of medicines no longer required. These

measures should help to protect the environment.

14.

DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED

15.

OTHER INFORMATION

Colourless Type I glass vials of 5 ml, 10 ml and 20 ml closed with a coated bromobutyl rubber stopper

and aluminium cap in a carton box.

Carton box pack sizes:

1 vial of 5 ml

1 or 5 vials of 10 ml

1 vial of 20 ml

Not all pack sizes may be marketed.

For any information about this veterinary medicinal product, please contact the local representative of

the marketing authorisation holder.

België/Belgique/Belgien

CP-Pharma Handelsgesellschaft mbH

Ostlandring 13

D-31303 Burgdorf

Allemagne

Lietuva

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Danmark

ScanVet Animal Health A/S

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DK-3480 Fredensborg

info@scanvet.dk

Danmark

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Polska

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Germany

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Suomi/Finland

Vet Medic Animal Health Oy

PL 27

FI-13721 Parola

vetmedic@vetmedic.fi

Suomi

Κύπρος

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D-31303 Burgdorf

Γερμανία

Sverige

VM Pharma AB

Box 45010

SE-104 30 Stockholm

info@vetmedic.se

Sverige

Latvija

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United Kingdom

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Germany