SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

DopramV Injection 20 mg/ml Solution for Injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substances:

Each 1ml contains:

Doxapram Hydrochloride 20.0 mg (equivalent to 17.5mg doxapram)

Excipient(s):

Chlorbutanol 5.0 mg as antimicrobial preservative

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection or sublingual administration.

A clear colourless solution.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs, cats, horses, calves and lambs.

4.2 Indications for use, specifying the target species

Respiratory stimulant

For dogs, cats and horses:

1. To stimulate respiration during and after general anaesthesia.

2. To speed awakening and return of reflexes after anaesthesia, when this

is considered beneficial.

Neonate dogs, cats, calves and lambs:

1. To initiate respiration following dystocia or Caesarean section.

2. To stimulate respiration following dystocia or Caesarean section.

4.3 Contraindications

None.

4.4 Special warnings for each target species

Special warnings include use in dogs which have been sedated with morphine (see 4.5).

Not to be used in known cases of epilepsy, cardiac dysfunction, hyperthyroidism or severe hepatic impairment.

4.5 Special precautions for use

i. Special precautions for use in animals

Dosage should be adjusted to meet the requirements of the situation. Adequate, but not excessive, doses should be used. A patent airway is essential. Reflexes should be checked periodically.

Excessive doses may produce hyperventilation which may be followed by reduced carbon dioxide tension in the blood, cerebral vasoconstriction, hypoxia, and possible brain damage.

Excessive doses administered to animals, during or following anaesthesia with

cyclopropane or halogenated hydrocarbon anaesthetics, may precipitate cardiac

arrhythmias.

The product should be used with extreme caution in dogs which have been sedated with morphine. Administration of a dose of 10mg/kg to such animals may be followed by convulsions.

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

Avoid self-injection with the product.

Avoid direct contact with skin and eyes. In the event of contact, wash with plenty of water. If irritation or other symptoms persist, seek medical advice.

Do not smoke, eat or drink when using the product.

Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

There may be adverse effects due to CNS stimulation, including respiratory difficulties and convulsions.

4.7 Use during pregnancy, lactation or lay

Foetal toxicity studies with doxapram in the rat and rabbit have not revealed any

teratogenic effects, nor evidence of any effect on male or female fertility.

4.8 Interaction with other medicinal products and other forms of interaction

(See also section 4.6 above)

The respiratory stimulant effects of doxapram in the dog were not blocked by anaesthetic doses of phenobarbitone sodium, pentobarbitone sodium, thiobarbitone sodium or secobarbitone sodium.

The respiratory depressant effects of morphine and pethidine were antagonised by doxapram in the cat and dog. In the cat, convulsions occurred after administration of morphine and doxapram but this species is highly susceptible to the convulsant activity of morphine.

Doxapram antagonised the spinal neuronal depressant effects of chlorpromazine, mephenesin and methocarbamol in non-anaesthetised cats.

Reversal of the respiratory depressant effects of large doses of ethanol was produced after administration of doxapram to rabbits and dogs.

Blood ethanol concentration was studied in the rat 2 - 3 hours after the concomitant administration of ethanol and doxapram. The blood ethanol concentration in the doxapram-treated animals was found to be significantly lower than that of the control animals.

The respiratory stimulant and pressor effects of doxapram were markedly potentiated by prior treatment with nialamide. Potentiation after pre-treatment with other monoamine oxidase inhibitors has not been studied.

Ref: A.H. Robins Report of 1st May, 1963.

4.9 Amounts to be administered and administration route

To ensure adequate dosing an insulin-type syringe must be used for administration to low bodyweight animals.

Post anaesthetic use: For intravenous use only.

Dogs and cats:

Following intravenous anaesthesia 2-5 mg/kg (0.1 - 0.25ml/kg) depending on response. Following inhalation anaesthesia 1-2mg/kg (0.05 - 0.1ml/kg) depending on response. Dosage should be adjusted for depth of anaesthesia and degree of respiratory depression. Dosage can be repeated in 15 to 20 minutes if necessary.

Horses:

Following intravenous or inhalation anaesthesia 0.5-1.0mg/kg (2.5-5.0ml/100kg) depending on response.

Dosage should be adjusted for depth of anaesthesia and degree of respiratory depression.

Neonatal use:

For intravenous or subcutaneous injection and for topical sublingual use.

Puppies:

1-5mg (0.05-0.25ml) depending on size of neonate and degree of respiratory depression.

Kittens:

1-2mg (0.05-0.1ml) depending on size of neonate and degree of respiratory depression.

Calves:

For intravenous, intramuscular, subcutaneous or sublingual use. 40-100mg (2.0-5.0ml) depending on size of neonate and degree of respiratory depression.

Lambs:

For intravenous, subcutaneous or sublingual use.

5-10mg (0.25-0.5ml) depending on size of neonate and degree of respiratory depression.

The action is rapid, usually beginning in a few seconds. The duration and intensity of response depends upon the dose, the condition of the animal at the time the drug is administered, and depth of anaesthesia. Repeated doses should not be given until the effects of the first dose have passed, and the condition of the patient requires it.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

See 4.5 above (special precautions for use).

In trials carried out on conscious cats to determine the total dose required to initiate

hyperventilation compared to the total dose required to produce convulsions, the

convulsive dose to respirogenic dose was calculated to be 38 : 1.

4.11 Withdrawal period(s)

For neonatal calves, lambs and horses, the meat withdrawal period is 28 days from

last administration.

Not for use in animals producing milk for human consumption.

5. PHARMACOLOGICAL PROPERTIES

ATC vet Code: QR07AB01

i) Pharmacodynamics

Published papers and a 1963 A.H. Robins report (Alphin et al) refer to the effect of

doxapram on the respiratory system.

Doxapram administered to dogs was found to increase minute volume primarily by an increase in tidal volume with a concomitant increase in PaO2, a decrease in PaCO2 and an increase in arterial pH.

The same 1963 A.H. Robins report (Alphin et al) and further published papers cover

the site and mechanism of action of doxapram. The evidence suggests that the action of doxapram is two-fold depending on the dose administered. Firstly, chemoreceptor stimulation results in a specific increase in the activity of the respiratory neurones in the medulla. Secondly, as the dose is increased, then non-specific central stimulation is superimposed upon these actions.

In addition, further references give information on the effect of doxapram on the

cardiovascular system, cerebral blood flow, the pituitary-adrenal axis, renal blood

flow, gastric secretion and various enzyme systems. The effect of doxapram in

haemorrhagic shock is also referred to, as is the convulsant activity of doxapram.

ii) Pharmacokinetics

The metabolism of doxapram has been studied in the rat, dog and man. Doxapram is extensively metabolised; the metabolites and unchanged doxapram are excreted in the bile and urine. The pharmacokinetic properties of doxapram can be described by a multi-compartmental model. Due to rapid redistribution the pharmacological effects of an intravenous injection of doxapram are terminated within 15-20 minutes following administration.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Chlorbutanol

Sodium hydroxide

Water for injections

6.2 Incompatibilities

Dopram V is incompatible with alkaline solutions such as aminophylline, frusemide and thiopentone.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 2 years.

Shelf-life after opening the immediate packaging: 28 days.

6.4. Special precautions for storage

Do not store above 25°C.

Protect from freezing.

Protect from light.

Following withdrawal of the first dose, the product should be used within 28 days.

6.5 Nature and composition of immediate packaging

20ml multidose Type I glass vial with a butyl rubber bung and aluminium overseal.

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 products should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Zoetis UK Limited

5th Floor, 6 St. Andrew Street

London

EC4A 3AE

8. MARKETING AUTHORISATION NUMBER

Vm42058/4038

9. DATE OF FIRST AUTHORISATION

Date:07 September 1994

10. DATE OF REVISION OF THE TEXT

Date:January 2014

APPROVED 8 January 2014