SEVOFLURANE BAXTER

Premedication should be selected according to the need of the individual patient, and at the discretion of the anaesthesiologist. Surgical anaesthesia The concentration of sevoflurane being delivered from a vaporizer during anaesthesia should be known.

This may be accomplished by using a vaporizer calibrated specifically for Sevoflurane. Anaesthesia induction Dosage should be individualised and titrated to the desired effect according to the patient’s age and clinical status. A short acting barbiturate or other intravenous induction agent may be administered followed by inhalation of sevoflurane.

0% sevoflurane, to a maximum of 8% in adults and children until the required depth of anaesthesia is achieved. In adults inspired concentrations of up to 5% sevoflurane usually produce surgical anaesthesia in less than two minutes. In children, inspired concentrations of up to 7% sevoflurane usually produce surgical anaesthesia in less than two minutes.

5-3% sevoflurane in O2 with or without concomitant use of N2O. 7% * Neonates are full-term gestational age. MAC in premature infants has not been determined. @ In 1 - < 3 year old pediatric patients, 60% N20/40% 02 was used. Emergence Emergence times are generally short following sevoflurane anesthesia.

Therefore, patients may require post-operative pain relief earlier. Elderly MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.

Paediatric population Refer to Table 1 for MAC values for paediatric patients according to age when used in oxygen with or without concomitant use of nitrous oxide.

v Summary of the safety profile As with all potent inhalational anaesthetics, sevoflurane can produce dose- dependent cardiac respiratory depression. Most of the adverse reactions are mild to moderate in severity and transient in duration.

Nausea and vomiting have been reported in the post-operative period – common symptoms following surgery and general anaesthesia – which may be due to the inhalational anaesthetic, other agents administered intra-operatively or post-operatively, or the patient’s reaction to the surgical procedure.

The most commonly reported adverse reactions were as follows:

In adult patients: hypotension, nausea and vomiting; In elderly patients: bradycardia, hypotension and nausea; and In paediatric patients: agitation, cough, vomiting and nausea. Tabulated summary of adverse reactions All reactions, at least possibly related to sevoflurane from clinical trials and post- marketing experience, are displayed in the Table below by MedDRA System Organ Class, Preferred Term and frequency.

The following frequency groupings are used: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1,000 and <1/100); rare (≥1/10,000 and <1/1,000); very rare (<1/10,000), including isolated reports. Post-marketing adverse reactions are reported voluntarily from a population with an unknown rate of exposure.

Therefore it is not possible to estimate the true incidence of adverse events and the frequency is “unknown”. The type, severity, and frequency of adverse reactions in sevoflurane patients in clinical trials were comparable to adverse reactions in reference-drug patients.

8 – Description of selected adverse reactions. 4. 8 – Paediatric population. 4 There have been very rare postmarketing reports of cardiac arrest in the setting of sevoflurane use. 5 Occasional cases of transient changes in hepatic function tests were reported with sevoflurane and reference agents.

Description of selected adverse reactions Transient increases in serum inorganic fluoride levels may occur during and after sevoflurane anaesthesia. Concentrations of inorganic fluoride generally peak within two hours of the end of sevoflurane anaesthesia and return within 48 hours to pre- operative levels.

In clinical trials, elevated fluoride concentrations were not associated with impairment of renal function. Rare reports of post-operative hepatitis exist. In addition, there have been rare post- marketing reports of hepatic failure and hepatic necrosis associated with the use of potent volatile anaesthetic agents, including sevoflurane.

4). Rare reports of hypersensitivity(including contact dermatitis, rash, dyspnoea, wheezing, chest discomfort, swelling face, eyelid edema, erythema, urticaria, pruritis bronchospasm, anaphylactic or anaphylactoid reactions have been reported particularly in association with long-term occupational exposure to inhaled anaesthetic agents, including sevoflurane.

4). Paediatric population The use of sevoflurane has been associated with seizures. Many of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Several cases reported no concomitant medications, and at least one case was confirmed by electroencephalography (EEG).

Although many cases were single seizures that resolved spontaneously or after treatment, cases of multiple seizures have also been reported. Seizures have occurred during, or soon after Sevoflurane induction, during emergence, and during […]

Sevoflurane should be administered only by persons trained in the administration of general anaesthesia. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and circulatory resuscitation must be immediately available.

) The concentration of sevoflurane being delivered from a vaporizer must be known exactly. As volatile anaesthetics differ in their physical properties, only vaporizers specifically calibrated for sevoflurane must be used. The administration of general anaesthesia must be individualized based on the patient's response.

Hypotension and respiratory depression increase as anaesthesia is deepened. During maintenance of anaesthesia, increasing the sevoflurane concentration results in dose- dependent decreases in blood pressure. An excessive reduction in blood pressure may be related to depth of anesthesia and in such instances may be corrected by decreasing the inspired sevoflurane concentration.

Due to sevoflurane’s insolubility in blood, hemodynamic changes may occur more rapidly than with some other volatile anaesthetics. Recovery from general anaesthesia should be assessed carefully before patients are discharged from the post-anaesthesia care unit.

Emergence is generally rapid following sevoflurane anaesthesia; therefore, patients may require early postoperative pain relief. Although recovery of consciousness following sevoflurane administration generally occurs within minutes, the impact on intellectual function for two or three days following anaesthesia has not been studied.

7). Patients with coronary disease As with all anaesthetics, maintenance of haemodynamic stability is important in order to avoid myocardial ischaemia in patients with coronary artery disease. 6). Patients undergoing neurosurgical procedures In patients at risk for elevations of ICP, sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.

Seizures Rare cases of seizures have been reported in association with sevoflurane use. Use of sevoflurane has been associated with seizures occurring in children and young adults as well as older adults with and without predisposing risk factors.

Clinical judgment is necessary before sevoflurane is used in patients at risk of seizures. In children the depth of anaesthesia should be limited. 4 – Paediatric population). Patients with renal injury Although data from controlled clinical studies at low flow rates are limited, findings taken from patient and animal studies suggest there is a potential for renal injury, which is presumed due to Compound A.

Animal and human studies demonstrate that sevoflurane administered for more than 2 MAC hours and at fresh gas flow rates of <2 L/min may be associated with proteinuria and glycosuria. 1. The level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established.

Consider all of the factors leading to Compound A exposure in humans, especially duration of exposure, fresh gas flow rate, and concentration of sevoflurane. Inspired sevoflurane concentration and fresh gas flow rate should be adjusted to minimize exposure to Compound A.

Sevoflurane exposure should not exceed 2 MAC hours at flow rates of 1 to <2 L/min. Fresh gas flow rates <1 L/min are not recommended. 5 mg/dl or 135 micromol/l); renal function should be monitored postoperatively. Patients with liver disease Very rare cases of mild, moderate or serious post-operative liver dysfunction or hepatitis (with or without jaundice) have been reported from post marketing experience.

Clinical judgement should be exercised when sevoflurane is used in patients with underlying liver problems or those who are receiving treatment with medications known to cause liver dysfunction. 8). Patients with mitochondrial disorders Caution should be exercised in administering general anesthesia, including sevoflurane, to patients with mitochondrial disorders.

, due to concomitant medications. Patients with repeated exposures to halogenated hydrocarbons, including sevoflurane, within a relatively short interval may have an increased risk of hepatic injury. Isolated reports of QT prolongation, very rarely associated with torsade de pointes (in exceptional cases, fatal), have been received.

Caution should be exercised when administering sevoflurane to susceptible patients.

Malignant hyperthermia:

In susceptible individuals, potent inhalation anaesthetic agents may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Rare cases of malignant hyperthermia have […]

Sevoflurane should not be used in patients with known or suspected hypersensitivity to sevoflurane or to other halogenated anaesthetics (e. g. history of liver function disorder, fever or leucocytosis of unknown cause after anesthesia with one of these agents).

Sevoflurane should not be used in patients with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction with jaundice, fever and eosinophilia after anaesthesia with sevoflurane.

Sevoflurane should not be used in patients with known or suspected genetic susceptibility to malignant hyperthermia. Sevoflurane is contraindicated in patients in whom general anesthesia is contraindicated.