In the event of overdosage, or what may appear to be overdosage, the following action should be taken:
Stop drug administration, establish a clear airway, and initiate assisted or controlled ventilation with pure oxygen.
Known sensitivity to FORANE (isoflurane, USP) or to other halogenated agents. Known or suspected genetic susceptibility to malignant hyperthermia.
Adverse reactions encountered in the administration of FORANE (isoflurane, USP) are in general dose dependent extensions of pharmacophysiologic effects and include respiratory depression, hypotension and arrhythmias.
Shivering, nausea, vomiting and ileus have been observed in the postoperative period.
As with all other general anesthetics, transient elevations in white blood count have been observed even in the absence of surgical stress. See WARNINGS for information regarding malignant hyperthermia and elevated carboxyhemoglobin levels.
During marketing, there have been rare reports of mild, moderate and severe (some fatal) postoperative hepatic dysfunction and hepatitis.
FORANE (isoflurane, USP) has also been associated with perioperative hyperkalemia (see WARNINGS).
Post-Marketing Events:The following adverse events have been identified during post-approval use of FORANE (isoflurane, USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of FORANE (isoflurane, USP) to these events cannot be established with certainty.
Cardiac Disorders: Cardiac arrest
Hepatobiliary Disorders: Hepatic necrosis, Hepatic failure.
FORANE (isoflurane, USP) may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.
Isoflurane has been shown to have a possible anesthetic-related fetotoxic effect in mice when given in doses 6 times the human dose. There are no adequate and well-controlled studies in pregnant women. Isoflurane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
FORANE (isoflurane, USP) is packaged in 100 mL and 250 mL amber-colored bottles.
| 100 mL | NDC 10019-360-40 |
| 250 mL | NDC 10019-360-60 |
FORANE (isoflurane, USP) is also supplied in the following aluminum bottles.
| 250 mL | NDC 10019-360-64 |
There is no specific work exposure limit established for FORANE (isoflurane, USP). However, the National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed at ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed one hour.
The predicted effects of acute overexposure by inhalation of FORANE (isoflurane, USP) include headache, dizziness or (in extreme cases) unconsciousness. There are no documented adverse effects of chronic exposure to halogenated anesthetic vapors (Waste Anesthetic Gases or WAGs) in the workplace. Although results of some epidemiological studies suggest a link between exposure to halogenated anesthetics and increased health problems (particularly spontaneous abortion), the relationship is not conclusive. Since exposure to WAGs is one possible factor in the findings for these studies, operating room personnel, and pregnant women in particular, should minimize exposure. Precautions include adequate general ventilation in the operating room, the use of a well-designed and well-maintained scavenging system, work practices to minimize leaks and spills while the anesthetic agent is in use, and routine equipment maintenance to minimize leaks.
StorageStore at room temperature 15°-30°C (59°-86°F). Isoflurane contains no additives and has been demonstrated to be stable at room temperature for periods in excess of five years.
Manufactured for: Baxter Healthcare Corporation, Deerfield, IL 60015 USA. For Product Inquiry 1 800 ANA DRUG (1-800-262-3784). Revised: February 2010
Use of 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 postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Malignant HyperthermiaIn susceptible individuals, isoflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and unstable blood pressure. (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) An increase in overall metabolism may be reflected in an elevated temperature, (which may rise rapidly early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the CO2 absorption system (hot canister). PaO2 and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., isoflurane), administration of intravenous dantrolene sodium, and application of supportive therapy. Such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base derangements. (Consult prescribing information for dantrolene sodium intravenous for additional information on patient management). Renal failure may appear later, and urine flow should be sustained if possible.
Since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable concentrations should be used. Hypotension and respiratory depression increase as anesthesia is deepened.
Increased blood loss comparable to that seen with halothane has been observed in patients undergoing abortions.
FORANE (isoflurane, USP) markedly increases cerebral blood flow at deeper levels of anesthesia. There may be a transient rise in cerebral spinal fluid pressure, which is fully reversible with hyperventilation.
PRECAUTIONS GeneralAs with any potent general anesthetic, FORANE (isoflurane, USP) should only be administered in an adequately equipped anesthetizing environment by those who are familiar with the pharmacology of the drug and qualified by training and experience to manage the anesthetized patient.
Regardless of the anesthetics employed, maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease 4,5,6,7.
FORANE (isoflurane, USP), like some other inhalational anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide, which may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 absorber canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of FORANE (isoflurane, USP).
As with other halogenated anesthetic agents, FORANE (isoflurane, USP) may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics (see CONTRAINDICATIONS).
REFERENCES
4. S. Reiz, et al, Anesthesiology 59:91-97, 1983
5. S. Slogoff and A.S. Keats, Anesthesiology 70:179-188, 1989
6. K.J. Tuman, et al, Anesthesiology 70:189-198, 1989
7. D.T. Mangano, Editorial Views, Anesthesiology 70:175-178, 1989
Laboratory TestsTransient increases in BSP retention, blood glucose and serum creatinine with decrease in BUN, serum cholesterol and alkaline phosphatase have been observed.
Carcinogenesis, Mutagenesis, Impairment of FertilitySwiss ICR mice were given isoflurane to determine whether such exposure might induce neoplasia. Isoflurane was given at ½, ⅛ and 1/32 MAC for four in-utero exposures and for 24 exposures to the pups during the first nine weeks of life. The mice were killed at 15 months of age. The incidence of tumors in these mice was the same as in untreated control mice, which were given the same background gases, but not the anesthetic.
Pregnancy Pregnancy Category CIsoflurane has been shown to have a possible anesthetic-related fetotoxic effect in mice when given in doses 6 times the human dose. There are no adequate and well-controlled studies in pregnant women. Isoflurane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoflurane is administered to a nursing woman.
Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by FORANE (isoflurane, USP), and the heart rate tends to be increased. The use of anticholinergic drugs is a matter of choice.
Inspired ConcentrationThe concentration of isoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using:
% isoflurane = 100 PvFv/FT (PA - PV)
Where: :
PA = Pressure of atmosphere
PV = Vapor pressure of isoflurane
FV=Flow of gas through vaporizer (mL/min)
FT = Total gas flow (mL/min)
Isoflurane contains no stabilizer. Nothing in the agent alters calibration or operation of these vaporizers.
InductionInduction with isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, or laryngospasm. These difficulties may be avoided by the use of a hypnotic dose of an ultra-short-acting barbiturate. Inspired concentrations of 1.5 to 3.0% isoflurane usually produce surgical anesthesia in 7 to 10 minutes.
MaintenanceSurgical levels of anesthesia may be sustained with a 1.0 to 2.5% concentration when nitrous oxide is used concomitantly. An additional 0.5 to 1.0% may be required when isoflurane is given using oxygen alone. If added relaxation is required, supplemental doses of muscle relaxants may be used.
The level of blood pressure during maintenance is an inverse function of isoflurane concentration in the absence of other complicating problems. Excessive decreases may be due to depth of anesthesia and in such instances may be corrected by lightening anesthesia.
Adverse reactions encountered in the administration of FORANE (isoflurane, USP) are in general dose dependent extensions of pharmacophysiologic effects and include respiratory depression, hypotension and arrhythmias.
Shivering, nausea, vomiting and ileus have been observed in the postoperative period.
As with all other general anesthetics, transient elevations in white blood count have been observed even in the absence of surgical stress. See WARNINGS for information regarding malignant hyperthermia and elevated carboxyhemoglobin levels.
During marketing, there have been rare reports of mild, moderate and severe (some fatal) postoperative hepatic dysfunction and hepatitis.
FORANE (isoflurane, USP) has also been associated with perioperative hyperkalemia (see WARNINGS).
Post-Marketing Events:The following adverse events have been identified during post-approval use of FORANE (isoflurane, USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of FORANE (isoflurane, USP) to these events cannot be established with certainty.
Cardiac Disorders: Cardiac arrest
Hepatobiliary Disorders: Hepatic necrosis, Hepatic failure.
DRUG INTERACTIONSIsoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O. See CLINICAL PHARMACOLOGY.
