Horses

Intravenous co-induction of anaesthesia with ketamine for smooth induction and intubation and profound muscle relaxation during anaesthesia.

Do not use in in animals with severe respiratory failure.

Do not use as a sole agent.

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

In case of renal or hepatic dysfunction or respiratory depression there may be greater risk associated with the use of the product. Use only according to the benefit/risk assessment by the responsible veterinarian.

Midazolam produces muscle relaxation; when used as a sole agent horses may be slightly sedated, but also restless or even agitated when they become ataxic/unstable.

Prolonged recovery time (prolonged recumbence and time to extubation) may be associated with use of the product.

The safety of repeated bolus dosing (at 0.06 mg/kg) at intervals of less than 4 days has not been established. Based on the pharmacokinetics of the active substance, care should be taken when administering repeated doses of midazolam within a 24 hour period to horses, particularly neonatal foals (i.e. foals less than 3 weeks old), obese horses and horses with hepatic impairment or conditions associated with reduced organ perfusion, due to the possibility of drug accumulation.

Care should be taken when administering the product to hypoalbuminaemic horses since these animals may have higher sensitivity to a given dose.

Before using combinations of midazolam with other veterinary medicinal products, the product literature for the other products should be observed.

Midazolam is a CNS depressant and can cause sedation and induction of sleep. Care should be taken to avoid self-injection. In case of accidental self-injection, seek medical advice immediately and show the package leaflet to the physician, but DO NOT DRIVE as sedation and impaired muscular function may occur.

Midazolam and its metabolites may be harmful for the unborn child, and are secreted into breastmilk in small amounts, thereby exerting a pharmacological effect on the nursing neonate. Pregnant and breastfeeding women should, therefore, take great care when handling this product and, in the event of exposure, seek medical advice immediately.

People with known sensitivity to midazolam or the excipients should avoid contact with the veterinary medicinal product.

This product contains benzyl alcohol and can cause skin irritation. Avoid contact with skin. In the case of contact with skin, wash with soap and water. If irritation persists, seek medical advice. Wash hands after use.

The product can cause eye irritation. Avoid contact with eyes. If the product comes into contact with the eyes, rinse the eyes immediately with plenty of water and seek medical attention if irritation persists.

Advice to physicians: Like other benzodiazepines, midazolam commonly causes drowsiness, ataxia, dysarthria anterograde amnesia, and nystagmus. Overdose of midazolam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and in rare cases to coma.

Monitor the patient's vital signs and institute supportive measures as indicated by the patient's clinical state. Respiratory and haemodynamic symptoms should be treated symptomatically.

Target species: Horses

*during recovery from anaesthesia

**upon induction of anaesthesia

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 section 'Contact details' of the package leaflet.

Laboratory studies in mice, rats and rabbits have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. In humans, use of benzodiazepines during the late third trimester of pregnancy or during labour has been associated with adverse effects in the foetus/neonate, including mild sedation, hypotonia, reluctance to suck, apnoea, cyanosis and impaired metabolic response to cold stress. Midazolam is found in low quantities in the milk of lactating animals.

The safety of the veterinary medicinal product during pregnancy and lactation has not been established in the target species. Use only according to the benefit/risk assessment by the responsible veterinarian.

Midazolam potentiates the effect of some sedative and anaesthetic agents, reducing the dose required, including alpha-2-agonists (detomidine, xylazine), propofol and some inhalational agents.

Concurrent use of midazolam with antihistamines (H2-receptor antagonists, e.g. cimetidine), barbiturates, local anaesthetics, opioid analgesics or CNS depressants may enhance the sedative effect.

In combination with other agents (e.g. opioid analgesics, inhalational anaesthetics), an increase in respiratory depression may be observed.

Erythromycin and azole antifungals (fluconazole, ketoconazole) inhibit the metabolism of midazolam, resulting in increased plasma midazolam concentrations and increased sedation.

Drugs that induce CYP450 mediated metabolism, such as rifampin, may decrease plasma concentrations and effects of midazolam.

For intravenous use.

Once the horse is properly sedated, anaesthesia is induced by intravenous injection of:

Midazolam at a dose of 0.06 mg per kg body weight, corresponding to 1.2 ml solution per 100 kg, in combination with ketamine at a dose of 2.2 mg per kg body weight. Midazolam and ketamine may be combined and administered in the same syringe.

To ensure a correct dosage, body weight should be determined as accurately as possible.

The symptoms of overdose are mainly an intensification of the pharmacological effects of midazolam: drowsiness, and muscle relaxation.

In case of accidental midazolam overdose, restlessness or agitation in combination with prolonged muscle weakness may develop when the ketamine effect of the combined midazolam-ketamine anaesthesia subsides.

Following a dose of 0.18 mg midazolam per kg body weight (3 times overdose) in combination with ketamine (2.2 mg/kg intravenously) after premedication with detomidine (20 µg/kg intravenously) the following effects attributable to midazolam were observed: poor recovery (more attempts to stand, more ataxia), a slight decrease of the haematocrit, respiratory depression - evidenced by a slight decrease of the respiratory rate, a lower pO2, a metabolic alkalosis and a slight increase of arterial pH - and a prolonged recovery. A dose of 0.3 mg midazolam per kg body weight (5 times overdose) using the same combination resulted in a violent recovery, i.e. horse trying to stand up, whilst still having profound muscle weakness.

The benzodiazepine antagonist flumazenil can be used to reverse effects associated with an overdose of midazolam, although clinical experience in horses is limited.

The product is not authorised for use in horses intended for human consumption.