Anesthetics, Muscle Relaxants and Premeds
= Additional active ingredients
Not less than 99.9% isoflurane.
PRESENTATION AND DOSSAGE
BOTTLE: 100 ml, 250 ml g
General anesthesia. Hospital only.
Isoflurane is contraindicated in patients with known sensitivity to isoflurane or other halogenated anaesthetics. It is also contraindicated in patients with known or suspected genetic .susceptibility to malignant hyperthermia
Vaporisers specially calibrated for isoflurane should be used so that the concentration of anaesthetic delivered can be .accurately controlled Hypotension and respiratory depression increase as .anaesthesia is deepened Reports of QT prolongation, associated with torsade de .pointes (in exceptional cases, fatal), have been received Caution should be exercised when administering isoflurane .to patients at risk for QT prolongation Caution should be exercised in administering general anesthesia, including isoflurane, to patients with mitochondrial .disorders Increased blood losses comparable with those found following anaesthesia with other inhalation agents have been recorded .with isoflurane in patients undergoing induced abortion Isoflurane relaxes the uterus muscle, and the lowest possible concentration of isoflurane should be used in obstetrical .(operations (please refer to section 4.6 Isolated cases of increased carboxyhaemoglobin have been reported with the use of halogenated inhalation agents with a –CF2H moiety (i.e., desflurane, enflurane and isoflurane). No clinically significant concentrations of carbon monoxide are .produced in the presence of normally hydrated absorbents Care should be taken to follow manufacturer’s instructions .for CO2 absorbents Isoflurane has been reported to interact with dry carbon dioxide absorbents to form carbon monoxide. In order to minimise the risk of formation of carbon monoxide in rebreathing circuits and the possibility of elevated carboxyhaemoglobin levels, carbon dioxide absorbent should .not be allowed to dry out Rare cases of extreme heat, smoke and/or spontaneous fire in the anesthesia machine have been reported during the administration of general anesthesia with drugs in this class ,when used in conjunction with desiccated CO2 absorbents ,.specifically those containing potassium hydroxide (e.g Baralyme). When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced before administration of isoflurane. The colour indicator of most CO2 absorbents .does not necessarily change as a result of desiccation Therefore, the lack of significant colour change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the .state of the colour indicator
General: As with any potent general anaesthetic, isoflurane should only be administered in an adequately equipped anaesthetising environment by those who are familiar with the pharmacology of the drug and qualified by training and experience to .manage the anaesthetised patient Since levels of anaesthesia may be altered quickly and easily with isoflurane, only vaporisers which deliver a predictable output with reasonable accuracy, or techniques during ,which inspired or expired concentrations can be monitored should be used. The degree of hypotension and respiratory depression may provide some indication of anaesthetic .depth Reports demonstrate that isoflurane can produce hepatic injury ranging from mild transient increases of liver enzymes .to fatal hepatic necrosis in very rare instances It has been reported that previous exposure to halogenated hydrocarbon anaesthetics, especially if the interval is less .than 3 months, may increase the potential for hepatic injury Cirrhosis, viral hepatitis or other pre-existing liver disease can be a reason to select an anaesthetic other than a halogenated .anaesthetic Regardless of the anaesthetics employed, maintenance of normal haemodynamics is important to the avoidance of myocardial ischaemia in patients with coronary artery .disease Isoflurane markedly increases cerebral blood flow at deeper levels of anaesthesia. There may be a transient rise in cerebral spinal fluid pressure which is fully reversible with .hyperventilation Isoflurane must be used with caution in patients with increased intracranial pressure. In such cases hyperventilation .may be necessary Use of isoflurane in hypovolaemic, hypotensive and debilitated patients has not been extensively investigated. A lower concentration of isoflurane is recommended for use in .these patients The action of non-depolarising relaxants is markedly .potentiated with isoflurane Isoflurane may cause a slight decrease in intellectual function for 2-4 days following anaesthesia. Small changes in moods and symptoms may persist for up to 6 days after administration. This must be taken into account when patients resume normal daily activities, including driving or operating .(heavy machinery (please refer to section 4.7 A potentiation of neuromuscular fatigue can be seen in patients with neuromuscular diseases, such as myasthenia gravis. Isoflurane should be used with caution in these .patients Isoflurane should be administered with caution to patients who can develop bronchoconstriction since bronchospasm .can occur Isoflurane may cause respiratory depression which may be augmented by narcotic premedication or other agents .causing respiratory depression Respiration should be supervised and if necessary, assisted . During the induction of anaesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of laryngospasm, particularly in children.
Children Under Two Years of Age: Caution should be exercised when isoflurane is used in .small children due to limited experience with this patientgroup. For full details see prescribing information.
Adverse reactions encountered in the administration of isoflurane are in general dose-dependent extensions of pharmaco-physiologic effects and include respiratory depression, hypotension and arrhythmias. Potential serious ,undesirable effects include malignant hyperthermia ,hyperkalemia, elevated serum creatine kinase, myoglobinuria anaphylactic reactions and liver adverse reactions. Shivering, nausea, vomiting and .ileus have been observed in the post-operative period. For full details see prescribing information.
Concomitant use of succinylcholine with inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the post-operative .period
Combinations advised against: Beta-sympathomimetic agents like isoprenaline and alphaand beta- sympathomimetic agents like adrenaline and noradrenaline should be used with caution during isoflurane .narcosis, due to a potential risk of ventricular arrhythmia Non-selective MAO-inhibitors: risk of crisis during the operation. Treatment should be stopped 15 days prior to .surgery
Combinations requiring precautions: in using Indirect-acting sympathomimetics (amphetamines and their derivatives, psychostimulants, appetite suppressants, ephedrine and its derivatives): risk of peri-operative hypertension. In patients undergoing elective surgery, treatment should ideally .be discontinued several days before surgery Adrenaline, by subcutaneous or gingival injections: risk of serious ventricular arrhythmia as a consequence of increased heart rate, although the myocardial sensitivity with respect to adrenaline is lower with the use of isoflurane than in the .case of halothane Cardiovascular compensation reactions may be impaired .by beta-blockers Inducers of CYP2E1: Medicinal products and compounds that increase the activity of cytochrome P450 isoenzyme CYP2E1, such as isoniazid and alcohol, may increase the metabolism of isoflurane and lead .to significant increases in plasma fluoride concentrations Use of isoflurane and isoniazid can increase the risk of .potentiation of the hepatotoxic effects :Calcium antagonists, in particular dihydropyridine derivates isoflurane may lead to marked hypotension in patients .treated with calcium antagonists Caution should be exercised when calcium antagonists are used concomitantly with inhalation anaesthetics due to the .risk of additive negative inotropic effect Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane .Muscle relaxants are markedly potentiated by isoflurane ,Neostigmine has an effect on the non-depolarising relaxants .but has no effect on the relaxing action of isoflurane itself MAC (minimum alveolar concentration) is reduced by concomitant administration of N20 in adults
Premedication: Drugs used for premedication should be selected for the individual patient bearing in mind the respiratory depressant effect of isoflurane. The use of anticholinergic drugs is a matter of choice, but may be advisable for inhalation.
induction: in paediatrics Induction A short-acting barbiturate or other intravenous induction agent is usually administered followed by inhalation of the isoflurane mixture. Alternatively, isoflurane with oxygen or .with an oxygen/nitrous oxide mixture may be used It is recommended that induction with isoflurane be initiated %at a concentration of 0.5%. Concentrations of 1.5% to 3.0 .usually produce surgical anaesthesia in 7 to 10 minutes.
Maintenance: Surgical levels of anaesthesia may be maintained with 1.0-2.5% isoflurane in oxygen/nitrous oxide mixtures. An additional 0.5-1.0% isoflurane may be required when given .with oxygen alone For caesarean section, 0.5-0.75% isoflurane in a mixture of oxygen/nitrous oxide is suitable to maintain anaesthesia .for this procedure Arterial pressure levels during maintenance tend to be inversely related to alveolar isoflurane concentrations in the absence of other complicating factors. Excessive falls in blood pressure may be due to depth of anaesthesia and in these circumstances, should be corrected by reducing the .inspired isoflurane concentration.
Elderly: As with other agents, lesser concentrations of isoflurane are normally required to maintain surgical anaesthesia in elderly .patients. See above for MAC values related to age. For full details see prescribing information.
As with other halogenated anaesthetics, hypotension and respiratory depression have been observed. Close monitoring of blood pressure and respiration is recommended. Supportive measures may be necessary to correct hypotension and respiratory depression resulting from excessively deep levels .of anaesthesia
PREGNANCY & LACTATION
Use in Pregnancy: There are no or limited amount of data from the use of isoflurane in pregnant women. Studies in animals have shown reproductive toxicity. Isoflurane should only be used during .pregnancy if the benefit outweighs the potential risk Isoflurane relaxes the uterus muscle, and the lowest possible concentration of isoflurane should be used in obstetrical .operations.
Use in Caesarean Section: Isoflurane, in concentrations up to 0.75%, has been shown to be safe for the maintenance of anaesthesia for caesarean.
Nursing Mothers: It is not known whether isoflurane/metabolites are excreted in ,human milk. Because many drugs are excreted in human milk caution should be exercised when isoflurane is administered .to a nursing woman
MANUFACTURER & DISTRIBUTER:
Manufacturer: Abbott Laboratories Israel
License Holder: CTS Ltd.