A clear, colourless, mobile, heavy liquid containing 1000mg/g isoflurane.

Inhalation vapour, Liquid.

To induce and maintain anaesthesia in horses, dogs, cats, ornamental birds, reptiles, rats, mice, hamsters, chinchillas, gerbils, guinea pigs and ferrets.

Piglets (up to 7 days of age): For general anaesthesia during the castration of male piglets in combination with the preoperative parenteral administration of a suitable analgesic to relieve postoperative pain.

Isoflurane should be administered using an accurately calibrated vaporiser in an appropriate anaesthetic circuit, since levels of anaesthesia may be altered rapidly and easily.

Isoflurane may be administered in oxygen or oxygen/nitrous oxide mixtures.

The MAC (minimal alveolar concentration in oxygen) or effective dose ED50 values and suggested concentrations given below for the target species should be used as a guide or starting point only. The actual concentrations required in practice will depend on many variables, including the concomitant use of other drugs during the anaesthetic procedure and the clinical status of the patient.

Isoflurane may be used in conjunction with other drugs commonly used in veterinary anaesthetic regimes for premedication, induction and analgesia. Some specific examples are given in the individual species information. The use of analgesia for painful procedures is consistent with good veterinary practice.

Recovery from Isoflurane anaesthesia is usually smooth and rapid. The analgesic requirements of the patient should be considered before the termination of general anaesthesia.

The lowest effective dose should be administered, and, as with all anaesthetics, the correct dose is the minimum that achieves the desired anaesthetic.

Although anaesthetics have a low potential for damage to the atmosphere, it is good practice to use charcoal filters with scavenging equipment, rather than to discharge them into the air.

The MAC for isoflurane in the horse is approximately 1.31%

Premedication: Isoflurane may be used with other drugs commonly used in veterinary anaesthetic regimes. The following drugs have been found to be compatible with isoflurane: acepromazine, alfentanil, atracurium, butorphanol, detomidine, diazepam, dobutamine, dopamine, guaiphenesin, ketamine, morphine, pentazocine, pethidine, thiamylal, thiopentone and xylazine. Drugs used for premedication should be selected for the individual patient. However, the potential interactions below should be noted.

Interactions: Detomidine and xylazine have been reported to reduce the MAC for Isoflurane in horses.

Induction: As it is not normally practicable to induce anaesthesia in adult horses using isoflurane, induction should be by the use of a short acting barbiturate such as thiopentone sodium, ketamine or guaiphenesin. Concentrations of 3 to 5% isoflurane may then be used to achieve the desired depth of anaesthesia in 5 to 10 minutes

Isoflurane at a concentration of 3 to 5% in a high flow oxygen may be used for induction in foals.

Maintenance: Anaesthesia may be maintained using 1.5% to 2.5% isoflurane.

Recovery: Recovery is usually smooth and rapid.

The MAC for isoflurane in the dog is approximately 1.28%.

Premedication: Isoflurane may be used with other drugs commonly used in veterinary anaesthetic regimes. The following drugs have been found to be compatible with isoflurane: acepromazine, atropine, butorphanol, buprenorphine, bupivacaine, diazepam, dobutamine, ephedrine, epinephrine, etomidate, glycopyrrolate, ketamine, medetomidine, midazolam, methoxamine, oxymorphone, propofol, thiamylal, thiopentone and xylazine. Drugs used for premedication should be selected for the individual patient. However, the potential interactions below should be noted.

Interactions: Morphine, oxymorphone, acepromazine, medetomidine, medetomidine plus midazolam have been reported to reduce the MAC for isoflurane in dogs.

The concomitant administration of midazolam/ketamine during isoflurane anaesthesia may result in marked cardiovascular effects, particularly arterial hypotension.

The depressant effects of propanolol on myocardial contractility are reduced during isoflurane anaesthesia, indicating a moderate degree of β-receptor activity.

Induction: Induction is possible by face mask using up to 5% isoflurane, with or without premedication.

Maintenance: Anaesthesia may be maintained using 1.5% to 2.5% isoflurane.

Recovery: Recovery is usually smooth and rapid.

The MAC for isoflurane in the cat is approximately 1.63%.

Premedication: Isoflurane may be used with other drugs commonly used in veterinary anaesthetic regimes. The following drugs have been found to be compatible with isoflurane: acepromazine, atracurium, atropine, diazepam, ketamine, and oxymorphone. Drugs used for premedication should be selected for the individual patient. However, the potential interactions below should be noted.

Interactions: Intravenous administration of midazolam- butorphanol has been reported to alter several cardio-respiratory parameters in isoflurane- induced cats as has epidural fentanyl and medetomidine. Isoflurane has been shown to reduce the sensitivity of the heart to adrenaline (epinephrine).

Induction: Induction is possible by face mask using up to 4% isoflurane, with or without premedication.

Maintenance: Anaesthesia may be maintained using 1.5% to 3% isoflurane.

Recovery: Recovery is usually smooth and rapid.

Few MAC/ED50 values have been recorded. Examples are 1.34% for the Sandhill crane, 1.45% for the racing pigeon, reduced to 0.89% by the administration of midazolam, and 1.44% for cockatoos, reduced to 1.08% by the administration of butorphanol analgesic.

The use of isoflurane anaesthesia has been reported for many species, from small birds such as zebra finches, to large birds such as vultures, eagles and swans.

Drug interactions/compatibilities: Propofol has been demonstrated in the literature to be compatible with isoflurane anaesthesia in swans.

Interactions: Butorphanol has been reported to reduce the MAC for isoflurane in cockatoos. Midazolam has been reported to reduce the MAC for isoflurane in pigeons.

Induction: Induction with 3 to 5% isoflurane is normally rapid. Induction of anaesthesia with propofol, followed by isoflurane maintenance, has been reported for swans.

Maintenance: The maintenance dose depends on the species and individual. Generally, 2 to 3% is suitable and safe.

Only 0.6 to 1% may be needed for some stork and heron species.

Up to 4 to 5% may be needed for some vultures and eagles.

3.5 to 4% may be needed for some ducks and geese.

Generally, birds respond very rapidly to changes in concentration of isoflurane.

Recovery: Recovery is usually smooth and rapid.

Isoflurane is considered by several authors to be the anaesthetic of choice for many species. The literature records its use on a wide variety of reptiles (eg. various species of lizard, tortoise, iguanas, chameleon and snakes).

The ED50 was determined in the desert iguana to be 3.14% at 35°C and 2.83% at 20°C.

Drug interactions/ compatibilities: No specific publications on reptiles have reviewed compatibilities or interactions of other drugs with isoflurane anaesthesia.

Induction: Induction is usually rapid at 2 to 4% isoflurane.

Maintenance: 1 to 3% is a useful concentration

Recovery: Recovery is usually smooth and rapid

Isoflurane has been recommended for anaesthesia of a wide variety of ‘small mammals’ (eg. rats, mouse, hamster, chinchilla, gerbil, guinea pig and ferret).

The MAC for mice has been cited as 1.34%, and for the rat as 1.38%, 1.46% and 2.4%.

Drug interactions/ compatibilities: No specific publications on small mammals have reviewed compatibilities or interactions of other drugs with isoflurane anaesthesia.

Induction: Isoflurane concentration 2 to 3%.

Maintenance: Isoflurane concentration 0.25 to 2%.

Recovery: Recovery is usually smooth and rapid.

PIGS (CASTRATION OF PIGLETS UP TO 7 DAYS OF AGE):

For piglets (up to 7 days of age)

Isoflurane concentration of up to 5Vol%, with oxygen as carrier gas with a flow rate of 2L/min.

The MAC value for isoflurane in pigs is 1.41-2.00%

Premedication:

Post-operative pain must be controlled by the timely parenteral administration of appropriate analgesics before the induction of anaesthesia.

Induction:

Isoflurane concentrations of up to 5 Vol % are used for the anaesthetic induction (with oxygen as carrier gas with a flow rate of 2L/min). After 70- 90 seconds a sufficient depth of anaesthesia is generally achieved. The actual duration required in practice depends on many variables. It is therefore imperative that the depth of anaesthesia be clinically checked by means of reflexes in each individual animal before castration is started. The inter- and dew claw reflexes are particularly suitable.

The castration may only be carried out under controlled supply of isoflurane, using a suitable inhalation device tested for the purpose. For the individual animal, it must be ensured that the mask used is leak-proof and that the exhaust air is filtered and discharged into a room (e.g. outdoors) where a sufficient rate of air exchange is achieved.

The product should only be used for uncomplicated castration procedures that are anticipated to be short in duration (maximum of 120 seconds for the entire procedure from the induction of anaesthesia to the end of castration of a piglet).

Recovery:

Recovery is usually smooth and rapid

Do not use in case of known susceptibility to malignant hyperthermia. Do not use in case of hypersensitivity to isoflurane or to other halogenated agents.

The ease and rapidity of alteration of the depth of anaesthesia with Isoflurane and its low metabolism, may be considered advantageous for its use in special groups of patients such as the old or young, and those with impaired hepatic, renal or cardiac function.

Piglets (up to 7 days of age):

When using a system which does not allow individual adjustment of the delivered dosage to each piglet, attention should be paid to the homogeneity of the group of animals to be anaesthetized simultaneously, in terms of age and weight. Care must be taken to ensure that the anaesthetic mask fits securely and tightly in order to guarantee a sufficient depth of anaesthesia for each individual animal.

To ensure safe and reliable anaesthesia, the sufficient depth of anaesthesia should be verified by appropriate reflex testing in each individual animal before the start of a painful procedure.

The use of a multimodal perioperative pain management is recommended.

Isoflurane has little or no analgesic properties. Adequate analgesia should always be given before surgery. The analgesic requirements of the patient should be considered before general anaesthesia is ended.

The use of the product in patients with cardiac disease should be considered only after a risk/ benefit assessment by the veterinarian.

It is important to monitor breathing and pulse for the frequency and its features. Respiratory arrest should be treated by assisted ventilation. It is important to maintain airways free and properly oxygenate tissues during the maintenance of anaesthesia. In the case of cardiac arrest, perform a complete cardio pulmonary resuscitation.

The metabolism of isoflurane in birds and small mammals, can be affected by decreases in body temperature, that may occur secondary to a high surface area to body weight ratio. Therefore, body temperature should be monitored and kept stable during treatment. Drug metabolism in reptiles is slow and highly dependent upon environmental temperature.

Reptiles may be difficult to induce with inhalation agents due to breath holding.

Like other inhalation anaesthetics of this type, isoflurane depresses the respiratory and cardiovascular systems.

When using isoflurane to anaesthetise an animal with a head injury, consideration should be given as to whether artificial ventilation is appropriate to help avoid increased cerebral blood flow by maintaining normal CO2 levels.

Piglets (up to 7 days of age):

Piglets should be observed for a sufficiently long time after castration in order to be able to recognise and, if necessary, treat post-operative bleeding. Care must be taken to ensure that the piglets do not cool down and, when awake, are returned to the mother sow as soon as possible. Do not use in piglets with anatomical anomalies in the genital area (e.g. cryptorchidism).

Isoflurane induces anaesthesia in humans. Moreover, it may induce liver damage and also allergic reactions to isoflurane have been reported. Fatigue, headache, or reduced reaction times have been reported at exposures below therapeutic doses. Splashes to the eye may induce irritation.

Do not breathe the vapour. Users should consult their National Authority for advice on Occupational Exposure Standards for isoflurane.

Operating rooms and recovery areas should be provided with adequate ventilation or scavenging systems to prevent the accumulation of anaesthetic vapour. Avoid using masking procedures for prolonged induction and maintenance of general anaesthesia. Use cuffed endotracheal intubation when possible for the administration of isoflurane during maintenance of general anaesthesia.

In the event of isoflurane odour or adverse health effects such as dizziness etc remove from the source of exposure and go to fresh air. In case of severe accidental exposure seek urgent medical assistance and show this label.

Isoflurane passes the placenta and transfers from maternal to foetal blood. Adverse effects on foetuses and pregnant animals were observed in laboratory animals. Pregnant and/or breast- feeding women should not have any contact with the product and should avoid operating rooms and animal recovery areas.

Avoid using masking procedures for prolonged induction and maintenance of general anaesthesia. Use cuffed endotracheal intubation when possible for the administration of isoflurane during maintenance of general anaesthesia.

Care should be taken when dispensing isoflurane, with any spillage removed immediately using an inert and absorbent material e.g. sawdust.

Contaminated work clothing should be taken off and washed before reuse.

Wash any splashes from skin and eyes, and avoid contact with the mouth.

Adverse effects on male fertility cannot be excluded. In male rats, effects on fertility parameters were observed after repeated exposure at higher concentrations. Prevent inhalation exposure to high concentrations by carefully following the instructions in the product information.

If severe accidental exposure occurs remove the operator from the source of exposure, seek urgent medical assistance and show this label.

Halogenated anaesthetic agents may induce liver damage. In case of isoflurane this is an idiosyncratic response very rarely seen after repeated exposure.

Piglets (up to 7 days of age)

In order to ensure that the safety of the workplace is maintained, castration may only be carried out using an appropriate inhalation device equipped with scavenging double masks.

The exposure of the user should be kept as low as possible. Operating theatres and recovery areas should be equipped with adequate ventilation to prevent accumulation of isoflurane vapours in the air breathed. In the case of underfloor ventilation, artificial ventilation must be set.

When the anaesthetic gas is used in a pig holding, a suitable isoflurane filling device should be used. Isoflurane tanks should preferably be filled outdoors, but at least in very well- ventilated rooms outside the rooms where animals are kept, with as few staff in the room as possible. It is recommended that the filling of isoflurane is monitored by additional personnel not involved in the filling process in case of an accidental exposure event.

Vaporizers should be switched off when not in use. It is advisable to have an isoflurane container with a capacity adapted to the amount needed for a whole day, so that the container does not need to be filled during anaesthesia.

It must be ensured that the mask used seals tightly for each individual piglet in order to avoid additional exposure of the workplace. Free escape from an unoccupied anaesthesia mask (no piglets in anaesthesia mask) must be prevented.

Advice to physician:Ensure a patient airway is clear and give symptomatic and supportive treatment. Note that adrenaline and catecholamines may cause cardiac arrhythmias.

Other precautions

Isoflurane is a gas with a global-warming potential and ozone depletion potential; thus it is good practice to use charcoal filters with scavenging equipment, rather than to discharge the gas into the air.

Isoflurane produces hypotension and respiratory depression in a dose- related manner.

Adverse reaction	Frequency
Cardiac arrhythmias	Rare	More than 1 but less than 10 animals in 10,000 animals
Transient bradycardia	Rare	More than 1 but less than 10 animals in 10.000
Malignant hyperthermia	Very rare	Less than 1 animal in 10,000 animals, including isolated reports

Isoflurane may produce excitations (tremors, restlessness), pale mucous membranes and prolonged recovery time.

Although Isoflurane can be used during cranial surgery and in patients with head injuries, increased cerebral blood flow and intracranial pressure can occur. Hyperventilating the patient can reduce the increased intracranial pressure..

Although Isoflurane has been used safely during caesarean section in the dog and cat, no full data are available on its use during pregnancy and lactation in the target species. Use in pregnant and lactating animals should, therefore only be considered following a risk/benefit assessment by the veterinary surgeon.

The action of muscle relaxants in man, especially those of the nondepolarising (competitive) type such as atracurium, pancuronium or vecuronium, is enhanced by isoflurane. Similar potentiation might be expected to occur in the target species, although there is little direct evidence to this effect. Concurrent inhalation of nitrous oxide enhances the effect of isoflurane in man and similar potentiation might be expected in animals.

The concurrent use of sedative or analgesic drugs is likely to reduce the level of isoflurane required to produce and maintain anaesthesia.For example, opiates, alpha-2-agonists, acepromazine, and benzodiazepines have been reported to reduce the MAC values.

The same was reported with the simultaneous use of non-steroidal anti-inflammatory drugs in the castration of piglets.

Isoflurane has a weaker sensitising action on the myocardium, to the effects of circulating dysrhythmogenic catecholamines, than halothane.

Delivery in nitrous oxide and premedication with agents such as acepromazine, opioids, benzodiazepines and alpha-2-adrenoreceptor agonists are compatible with isoflurane use; however, the concurrent use of sedative or analgesic drugs is likely to reduce the level of isoflurane required to produce and maintain anaesthesia.

Isoflurane may be degraded to carbon monoxide by dried carbon dioxide absorbents.

For reptiles and small mammals, there are no data available.

Isoflurane overdose may result in profound respiratory depression. Therefore, respiration must be monitored closely and supported when necessary with supplementary oxygen and/ or assisted ventilation.

In cases of severe cardiopulmonary depression, administration of isoflurane should be discontinued, the breathing circuit should be flushed with oxygen, the existence of a patent airway ensured, and assisted or controlled ventilation with pure oxygen initiated. Cardiovascular depression should be treated with plasma expanders, pressor agents, antiarrhythmic agents or other appropriate techniques.

Horses: meat and offal 2 days

Do not use in mares producing milk for human consumption.

Pigs (piglets up to 7 days of age): Meat and offal: 2 days

Do not store above 25°C. Protect from direct sunlight & direct heat. Store in tightly closed original container.

Any unused product or waste material should be disposed of in accordance with local requirements.

100ml or 250ml amber bottle fitted with a black phenolic urea/polypropylene screw cap with a low-density polyethylene cone insert.

Piramal Critical Care Limited, Suite 4, Ground Floor, Heathrow Boulevard - East Wing, 280 Bath Road, West Drayton, UB7 0DQ, United Kingdom