Isoflurane

FORANE (isoflurane, USP), a nonflammable liquid administered by vaporizing, is a general inhalation anesthetic drug. It is 1-chloro-2, 2,2-trifluoroethyl difluoromethyl ether, and its structural formula is:

Some physical constants are:

Molecular weight..............................184.5
Boiling point at 760 mm Hg...................48.5°C (uncorr.)
Refractive index n20D..........................1.2990-1.3005
Specific gravity 25°/25°C....................1.496
Vapor pressure in mm Hg**

20°C........238
25°C...........295
30°C...........367
35°C...........450

**Equation for vapor pressure calculation:
log10Pvap = A + B/T where A = 8.056 T
B = -1664.58
T = °C + 273.16 (Kelvin)

Partition coefficients at 37°C:

Water/gas.................0.61
Blood/gas.................1.43
Oil/gas.......................90.8

Partition coefficients at 25°C - rubber and plastic

Conductive rubber/gas.................62.0
Butyl rubber/gas.................75.0
Polyvinyl chloride/gas.................110.0
Polyethylene/gas.................~2.0
Polyurethane/gas................. ~1.4
Polyolefin/gas .................~1.1
Butyl acetate/gas................. ~2.5
Purity by gas chromatography ................. > 99.9%
Lower limit of flammability in oxygen or nitrous oxide at 9 joules/sec. and 23°C.................None
Lower limit of flammability in oxygen or nitrous oxide at 900 joules/sec. and 23°C.................Greater than useful concentration in anesthesia.

Isoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers. Isoflurane has a mildly pungent, musty, ethereal odor. Samples stored in indirect sunlight in clear, colorless glass for five years, as well as samples directly exposed for 30 hours to a 2 amp, 115 volt, 60 cycle long wave U.V. light were unchanged in composition as determined by gas chromatography. Isoflurane in one normal sodium methoxide-methanol solution, a strong base, for over six months consumed essentially no alkali, indicative of strong base stability. Isoflurane does not decompose in the presence of soda lime (at normal operating temperatures), and does not attack aluminum, tin, brass, iron or copper.

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.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Isoflurane falls into category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

OR

There are no well-controlled studies that have been done in pregnant women. Isoflurane should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

OR

No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Isoflurane should be given to a pregnant woman only if clearly needed.

Take isoflurane exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Isoflurane dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Isoflurane is available in the following doses:

• Isoflurane 100% Inhalation Liquid

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
• Very bad dizziness or passing out.
• Trouble breathing, slow breathing, or shallow breathing.
• A heartbeat that does not feel normal.
• Muscle stiffness.
• Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
• This medicine may cause a very bad and sometimes deadly problem called malignant hyperthermia. Call your doctor right away if you have a fast heartbeat, fast breathing, fever, or spasm or stiffness of the jaw muscles.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

• If you need to store isoflurane at home, talk with your doctor, nurse, or pharmacist about how to store it.

Known sensitivity to Isoflurane or to other halogenated agents.  Known or suspected genetic susceptibility to malignant hyperthermia.

Adverse reactions encountered in the administration of Isoflurane 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.

Isoflurane has also been associated with perioperative hyperkalemia (see WARNINGS

).

Post-Marketing Events

The following adverse events have been identified during post-approval use of Isoflurane.  Due to the spontaneous nature of these reports, the actual incidence and relationship of Isoflurane to these events cannot be established with certainty.

Cardiac Disorders: Cardiac arrest

Hepatobiliary Disorders : Hepatic necrosis, Hepatic failure.

Occupational Caution
There is no specific work exposure limit established for Isoflurane. However, the National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed at ceiling concentrations greater than 2ppm of any halogenated anesthetic agent over a sampling period not to exceed one hour.

The predicted effects of acute overexposure by inhalation of Isoflurane 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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Shivering.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.