Dogs and cats.

Analgesia in dogs and cats.

Premedication for general anaesthesia or neuroleptanalgesia in dogs and cats in combination with a neuroleptic drug.

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

Do not use in animals with advanced respiratory failure.

Do not use in animals with severe liver and renal dysfunction.

Due to the variable individual response to methadone, animals should be monitored regularly to ensure sufficient efficacy for the desired duration of effect.

Use of the product must be preceded by a thorough clinical examination.

In cats, pupil dilation is seen long after the analgesic effect has disappeared. It is therefore not an adequate parameter to assess clinical efficacy of the administered dose.

Greyhounds may require higher doses than other breeds to achieve efficacious plasma levels.

Methadone may occasionally cause respiratory depression and, as with other opioid drugs, care should be taken when treating animals with impaired respiratory function, or animals that are receiving drugs that can cause respiratory depression. To ensure safe use of the product, treated animals should be monitored regularly, including examination of heart rate and respiratory rate.

As methadone is metabolised by the liver, its intensity and duration of action may be affected in animals with impaired liver function.

In cases of renal, cardiac or hepatic dysfunction, or shock, there may be greater risk associated with the use of the veterinary medicinal product.

The safety of methadone has not been demonstrated in dogs less than 8 weeks and cats less than 5 months of age.

The effect of an opioid on head injury is dependent on the type and severity of the injury and the respiratory support supplied.

Safety has not been fully evaluated in clinically compromised cats.

Due to the risk of excitation, repeated administration in cats should be used with care.

The benefit/risk ratio for using the veterinary medicinal product should be made by the attending veterinarian.

Methadone can cause respiratory depression following spillage onto the skin or accidental self-injection. Avoid skin, eye and mouth contact, and wear impermeable gloves when handling the product. In cases of spillage onto the skin, or splashing into the eyes, wash immediately with large amounts of water. Remove contaminated clothes.

People with known hypersensitivity to methadone should avoid contact with the veterinary medicinal product. Methadone has the potential to cause stillbirths. The veterinary medicinal product should not be administered by pregnant women.

In the case of accidental self-injection, seek medical advice immediately and show the package leaflet or label to the physician but DO NOT DRIVE as sedation may occur.

To the physician: Methadone is an opioid whose toxicity may cause clinical effects including respiratory depression or apnoea, sedation, hypotension and coma. When respiratory depression occurs controlled ventilation should be installed. Administration of the opioid antagonist naloxone to reverse the symptoms is recommended.

Cats1:

1 All reactions were transient.

2 Mild.

Dogs1:

1 All reactions were transient.

2 Mild.

3 Occasional, within first hour post dose.

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 also the last section of the package leaflet for respective contact details.

Pregnancy and lactation:

The safety of the veterinary medicinal product has not been established during pregnancy and lactation. Methadone diffuses across the placenta. The use is not recommended during pregnancy or lactation.

Fertility:

Studies in laboratory animals have shown adverse effects on reproduction.

For concurrent use with neuroleptics refer to Amounts to be administered and administration route.

Methadone can potentiate the effects of analgesics, central nervous system inhibitors and substances that cause respiratory depression. Concomitant or subsequent use of the veterinary medicinal product with buprenorphine may lead to lack of efficacy.

To ensure accuracy of dosing, bodyweight should be accurately measured and an appropriately calibrated syringe should be used to administer the product.

Dogs: 0.5-1 mg Methadone HCl per kg body weight, SC, IM or IV (corresponding to 0.05-0.1 ml/kg)

Cats: 0.3-0.6 mg Methadone HCL per kg body weight, IM (corresponding to 0.03-0.06 ml/kg)

As individual response to methadone is varied, and depends partly on the dosage, the age of the patient, individual differences in pain sensitivity and general condition, the optimal dosing regimen should be individually based.

In dogs, onset of action is 1 hour following subcutaneous administration, approximately 15 minutes following intramuscular injection and within 10 minutes following intravenous injection. Duration of effect is approximately 4 hours following intramuscular or intravenous administration.

In cats, onset of action is 15 minutes following administration, and the duration of effect is 4 hours on average.

The animal should be examined regularly to assess if additional analgesia is subsequently required.

Dogs: Methadone HCl 0.5-1 mg/kg body weight, IV, SC or IM (corresponding to 0.05-0.1 ml/kg)

Combinations eg:

- Methadone HCl 0.5 mg/kg body weight, IV (corresponding to 0.05 ml/kg), + eg midazolam or diazepam

Induction with propofol, maintenance on isoflurane in oxygen.

- Methadone HCl 0.5 mg/kg body weight, IV (corresponding to 0.05 ml/kg), + eg acepromazine

Induction with thiopentone or propofol to effect, maintenance on isoflurane in oxygen or induction with diazepam and ketamine.

- Methadone HCl 0.5-1.0 mg/kg body weight, IV or IM (corresponding to 0.05-0.1 ml/kg), + α2-agonist (eg xylazine or medetomidine)

Induction with propofol, maintenance on isoflurane in oxygen in combination with fentanyl or total intravenous anaesthesia (TIVA) protocol: maintenance on propofol in combination with fentanyl.

TIVA protocol: induction propofol, to effect. Maintenance on propofol and remifentanil. Chemical-physical compatibility has only been demonstrated for dilutions 1:5 with the following solutions for infusion: sodium chloride 0.9%, Ringer’s solution, and glucose 5%.

Cats: Methadone HCl 0.3-0.6 mg/kg body weight, IM (corresponding to 0.03-0.06 ml/kg)

- Induction with benzodiazepine (eg midazolam) and dissociative (eg ketamine).

- With a tranquiliser (eg acepromazine) and NSAID (meloxicam) or sedative (eg α2-agonist).

- Induction with propofol, maintenance on isoflurane in oxygen.

Doses are dependent on the desired degree of analgesia and sedation, desired duration of effect and the concurrent use of other analgesics and anaesthetics.

When used in combination with other products, lower dosages can be used.

For safe use with other veterinary medicinal products, reference must be made to the relevant product literature.

A 1.5 fold overdose resulted in the effects described in Adverse reactions.

Cats: In case of overdoses (>2 mg/kg) the following signs can be observed: increased salivation, excitation, hind leg paralysis and loss of righting reflex. Seizures, convulsion and hypoxia were also recorded in some cats. A dose of 4 mg/kg could be fatal in cats. Respiratory depression has been described.

Dogs: Respiratory depression has been described.

Methadone can be antagonised by naloxone. Naloxone should be given to effect. A starting dose of 0.1 mg/kg intravenously is recommended.