Sevoflurane Piramal

Sevoflurane Piramal

sevoflurane

Manufacturer:

Piramal Critical Care

Distributor:

Evercare Pharma
Full Prescribing Info
Contents
Sevoflurane.
Description
The formulation contains sevoflurane (C4H3F7O), which is a halogenated general inhalation anaesthetic drug.
Sevoflurane is a nonflammable, pleasant-smelling, non-explosive and volatile liquid. It is a clear, colorless, stable liquid containing no additives or chemical stabilizers. It is non-pungent, miscible with ethanol, ether, chloroform and petroleum benzene; and is slightly soluble in water.
No discernible degradation occurs in the presence of strong acids or heat.
Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper-beryllium alloy.
Sevoflurane has the following physical properties: Gram Molecular Weight: 200. Boiling Point at 760 mmHG: 58.5°C. Refractive Index: 1.274-1.276. Density: 1.52. Saturated Vapour Pressure at 20°C: 157 mmHg. Odor: Non-irritating, similar to ether. Appearance: Clear, colourless. Additives/Chemical Stabilizers: None. Stability in Moist Soda Lime at 40, 60 or 80°C: Unstable.
Partition Coefficients at Normal Body Temperature: Water/Gas: 0.36. Blood/Gas: 0.63-0.69. Olive Oil/Gas: 47.2-53.9. Brain/Blood: 1.7. Heart/Blood: 1.78. Liver/Blood: 1.85. Kidney/Blood: 1.15.
Mean Partition Coefficients at 25°C (Component/Gas): Conductive Rubber: 14. Butyl Rubber: 7.7. Polyvinylchloride: 17.4. Polyethylene: 1.3. Purity by Gas Chromatography: 99.975% or better.
Flammability: Not flammable.
Action
Pharmacology: Sevoflurane is an inhalation anaesthetic agent for use in induction and maintenance of general anaesthesia. Administration has been associated with a smooth, rapid loss of consciousness during inhalation induction and a rapid recovery following discontinuation of anaesthesia. Minimum alveolar concentration (MAC) of sevoflurane in oxygen reported for a 40-year adult is 2.1%. The MAC of sevoflurane decreases with age and with the addition of nitrous oxide.
Induction is accomplished with a minimum of excitement or of signs of upper respiratory irritation, no evidence of excessive secretions within the tracheobronchial tree and no central nervous system stimulation. Changes in the depth of sevoflurane anaesthesia rapidly follow changes in the inspired concentration. The times for induction and recovery were reduced in paediatric who received sevoflurane in clinical studies.
The depth of anaesthesia changes rapidly following changes in the inspired concentration of sevoflurane. Emergence and recovery are particularly rapid. Therefore, patients may require early postoperative pain relief.
As with all other inhalation agents, sevoflurane depresses cardiovascular function in a dose-related fashion. No evidence of seizure has been documented.
Sevoflurane has minimal effect on intracranial pressure (ICP) and preserved carbon dioxide, responsiveness in patients with normal ICP. Its safety has not been investigated in patients with a raised ICP. Sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers eg, hyperventilation in those patients who are at risk for elevations of ICP.
The low solubility of sevoflurane in blood should result in alveolar concentrations which rapidly increase upon induction and rapidly decrease upon cessation of the inhaled agent.
In humans, <5% of the absorbed sevoflurane is metabolised. The rapid and extensive pulmonary elimination of sevoflurane minimise the amount of anaesthetics available for metabolism. Sevoflurane is defluorinated via cytochrome P450 (CYP) 2E1 resulting in the production  of hexafluoroisopropanol (HFIP) with release of inorganic fluoride and carbon dioxide (or a carbon fragment). HFIP is then rapidly conjugated with glucuronic acid and excreted in the urine.
The metabolism of sevoflurane may be increased by known CYP2E1 inducers (eg, isoniazid and alcohol) but it is not inducible by barbiturates.
Transient increases in serum inorganic fluoride levels may occur during and after sevoflurane anaesthesia.
Generally, concentrations of inorganic fluoride peak within 2 hrs of the end of sevoflurane anaesthesia and return within 48 hrs to pro-operative levels.
Indications/Uses
For induction and maintenance of general anaesthesia for surgery in both adults and children.
Dosage/Direction for Use
Premedication: Premedication should be selected at the discretion of the anaesthetist, taking into consideration the need of the individual patient. The use of anticholinergic drugs is a matter of choice.
Induction: Dosage should be individualised and titrated to the desired effect according to the patient's age and clinical status.
Anaesthesia can be induced in adults and children with sevoflurane.
A short-acting barbiturate or other IV induction agent may be administered followed by inhalation of sevoflurane.
Induction with sevoflurane may be achieved in oxygen or in combination with oxygen-nitrous oxide mixtures.
Adults: Inspired concentrations of up to sevoflurane 5% usually produce surgical anaesthesia in <2 min.
Children: Inspired concentrations of up to sevoflurane 7% usually produce surgical anaesthesia in <2 min.
Unpremedicated Patients: Inspired concentrations of up to sevoflurane 8% may be used.
Maintenance:  Surgical levels of anaesthesia can usually be achieved with concentrations of sevoflurane 0.5-3% with or without concomitant use of nitrous oxide.
Elderly: To maintain surgical anaesthesia in these patients, lesser concentrations of sevoflurane are normally required. (See table.)
Minimum alveolar concentration values for sevoflurane decrease with age and with the addition of nitrous oxide.
The following table indicates the average MAC values for different age groups:

Click on icon to see table/diagram/image

Emergence: Emergence time are generally short following sevoflurane anaesthesia. Therefore, patients may require early postoperative pain relief.
Overdosage
In the event of overdosage, stop drug administration, establish a clear airway and initiate assisted or controlled ventilation with pure oxygen and maintain adequate cardiovascular function.
Contraindications
Known sensitivity to sevoflurane. Patients with known or suspected genetic susceptibility to malignant hyperthermia.
Special Precautions
General Precautions: Sevoflurane should be administered only by trained personnel in the administration of general anaesthesia.
Ensure that facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and circulatory resuscitation are immediately available.
Sevoflurane should be delivered via a vaporiser specifically calibrated for use with sevoflurane so that the concentration delivered can be accurately controlled.
Hypotension and respiratory depression increase as anaesthesia is deepened.
Sevoflurane should be used in caution in patients with renal insufficiency.
Sevoflurane may present an increased risk in patients with known sensitivity to volatile halogenated anaesthetic agents.
Rare cases of seizures have been reported in association with sevoflurane use.
Maintenance of Anaesthesia:  During the maintenance of anaesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. Excessive decrease in blood pressure may be related to depth of anaesthesia and in such instances may be corrected by decreasing the inspired concentration of sevoflurane.
Malignant Hyperthermia: The recovery from general anaesthesia should be assessed carefully before patients are discharged from the recovery room. 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. The syndrome may include nonspecific features eg, muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and unstable blood pressure. Treatment includes discontinuation of triggering agents (eg, sevoflurane), administration of dantrolene sodium IV and application of supportive therapy. Renal failure may appear later and urine flow should be monitored and sustained if possible.
Perioperative Hyperkalemia: Use of inhaled anaesthetic agents has been associated with very rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in children during the postoperative period. The condition has been described in patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy. Use of suxamethonium has been associated with most, but not all of these cases. These patients showed evidence of muscle damage with increased serum creatinine kinase concentration and myoglobinuria. These patients did not have classical signs of malignant hyperthermia eg, muscle rigidity, rapid increase in body temperature or increased oxygen uptake and carbon dioxide production. Prompt and vigorous treatment for hyperkalaemia and arrhythmias is recommended.
Subsequent evaluation for latent neuromuscular disease is indicated.
Renal Function:  Because clinical experience in administering sevoflurane to patients with renal insufficiency (creatinine >1.5 mg/dL) is limited, its safety in these patients has not been established. Limited pharmacology data in these patients appear to suggest that the half-life (t½) of sevoflurane may be increased. The clinical significance is unknown at this time. Thus, sevoflurane should be used with caution in these patients.
Hepatic Function:  Results of evaluations of laboratory parameters (eg, ALT, AST, alkaline phosphatase and total bilirubin, etc.), as well as investigator-reported incidence of adverse reactions relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. However, patients with severe hepatic dysfunction were not investigated.
Occasional cases of transient changes in postoperative hepatic function tests were reported with both sevoflurane and reference agents. Sevoflurane was found to be comparable to isoflurane with regard to these changes in hepatic function.
Very rare cases of mild, moderate and severe postoperative hepatic dysfunction or hepatitis with or without jaundice have been reported from post-marketing experiences. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction.
Compound A: Sevoflurane produces low levels of Compound A [pentafluoroisopropenyl fluoromethyl ether (PIFE)] and trace amounts of Compound B [pentafluoromethoxy isopropyl fluoromethyl ether (PMFE)], when in direct contact with carbon dioxide absorbents. Levels of Compound A may increase with: Increase in canister temperature, increase in anaesthetic concentration; decrease in gas flow rate and with the use of Baralyme rather than soda lime. (See also Pharmaceutical Precautions)
It is reported from some studies in rats, nephrotoxicity was seen in animals exposed to levels of Compound A in excess of those usually seen in routine clinical practice. The mechanism of this renal toxicity in rats is unknown and its relevance to man has not been established.
Replacement of Desiccated Carbon Dioxide Adsorbents: The exothermic reaction that occurs with sevoflurane and carbon dioxide absorbent is increased when the carbon dioxide becomes desiccated such as after an extended period of dry gas flowthrough the carbon dioxide absorbent canisters. Rare cases of extreme heat, smoke and/or spontaneous fire in the anaesthesia machine have been reported during sevoflurane use in conjunction with the use of desiccated carbon dioxide absorbent. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the carbon dioxide absorbent canister.
When a clinician suspects that the carbon dioxide absorbent may be desiccated, it should be replaced before administration of sevoflurane. The color indicator of most carbon dioxide absorbents does not necessarily change as a result of desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. Carbon dioxide absorbents should be replaced routinely regardless of the state of the color indicator.
Laboratory Findings: Transient elevations in glucose and white blood cell count may occur as with use of other anaesthetic agents.
Occasional cases of transient changes in hepatic function tests were reported with sevoflurane.
Pharmaceutical Precautions: Sevoflurane is chemically stable. As with some halogenated anaesthetics, minor degradation occurs through direct contact with carbon dioxide absorbents. The extent of degradation is clinically insignificant and no dose adjustments or change in clinical practice is necessary when rebreathing circuits are used. Higher levels of Compound A are obtained when using Baralyme rather than soda lime.
Effects on the Ability to Drive or Operate Machinery: As with other anaesthetic agents, patients should be advised that performance of activities requiring mental alertness (eg, operating hazardous machinery) may be impaired for some time after general anaesthesia. Patients should not be allowed to drive for a suitable period after sevoflurane anaesthesia.
Use in pregnancy & lactation: Sevoflurane should be used during pregnancy only if clearly needed.
It is not known whether sevoflurane is excreted in human milk therefore caution should be exercised when sevoflurane is administered to a nursing woman.
Use In Pregnancy & Lactation
Sevoflurane should be used during pregnancy only if clearly needed.
It is not known whether sevoflurane is excreted in human milk therefore caution should be exercised when sevoflurane is administered to a nursing woman.
Adverse Reactions
Generally well tolerated. Most adverse events are mild to moderate in severity and transient. Nausea and vomiting are commonly observed in the postoperative period at a similar incidence to those found in other inhalation anaesthetics. In addition to nausea and vomiting, other frequent adverse reactions were: Adults:  Hypotension. Elderly: Hypotension and bradycardia. Children: Agitation and increased cough.
Less frequent adverse reactions associated with sevoflurane administration were: Agitation, somnolence, chills, bradycardia, dizziness, increased salivation, respiratory disorder, hypertension, tachycardia, laryngismus, fever, headache, hypothermia, increased SGOT.
Occasionally reported adverse reactions associated with the administration of sevoflurane includes: Arrhythmias, increased LDH, increased SGPT, hypoxia, apnoea, leukocytosis, ventricular extrasystoles, supraventricular extrasystoles, asthma, confusion, increased creatinine, urinary retention, glycosuria, atrial fibrillation, complete AV block, bigeminy, leucopenia. Allergic reactions eg, rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions have also been reported. As with all potent inhaled anaesthetics, sevoflurane may cause dose-dependent cardiorespiratory depression.
Convulsions may occur extremely rarely following sevoflurane administration, particularly in children.
There have been very rare reports of pulmonary oedema.
Drug Interactions
The action of nondepolarising muscle relaxants is markedly potentiated with sevoflurane, therefore, when administered with sevoflurane, dosage adjustments of these agents should be made.
Sevoflurane is similar to isoflurane in the sensitisation of the myocardium to the arrhythmogenic effect of exogenously administered adrenaline.
Minimum alveolar concentration (MAC) values for sevoflurane decrease with the addition of nitrous oxide as indicated in the previously mentioned table on Dosage & Administration.
As with other agents, lesser concentrations of sevoflurane may be required following use of an IV anaesthetic eg, propofol. The metabolism of sevoflurane may be increased by known inducers of CYP2E1 (eg, isoniazid and alcohol), but it is not inducible by barbiturates.
Caution For Usage
Instructions for Use: Some halogenated anaesthetics have been reported to interact with dry carbon dioxide absorbent to form carbon monoxide. To date, there is no evidence that this can occur with sevoflurane. However, in order to minimise the risk of carbon monoxide formation in rebreathing circuits and the possibility of elevated carboxy-haemoglobin levels, carbon monoxide absorbents should not be allowed to dry out.
Storage
Do not store above 25°C. Do not refrigerate. Keep cap tightly closed.
ATC Classification
N01AB08 - sevoflurane ; Belongs to the class of halogenated hydrocarbons. Used as general anesthetics.
Presentation/Packing
Inhalation liqd 100% x 250 mL.
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