Composition:

ISOFLURANE- Ibn Hayyan is available in unit packages of 100 ml and 250 ml of Isoflurane administered by vaporizing .

Pharmacological properties:

Isoflurane is non-flammable general inhalation anesthetic which contains no additive or stabilizer. The MAC (minimum alveolar concentration) in man is as follows:
             Age                          Ave. Concentration         Ave. Concentration

100% Oxygen                        70% N 0 ₂
26±4                                 1.28                                     0.56
44±7                                 1.15                                     0.50
64±5                                 1.05                                     0.37

Induction of and recovery from Isoflurane anesthesia are rapid. Pharyngeal and laryngeal reflexes are readily obtunded. The level of anesthesia may be changed rapidly with Isoflurane. Isoflurane is a profound respiratory depressant. Respiration must be monitored closely and supported when necessary.

Nitrous oxide diminishes the inspiratory concentration of Isoflurane required to reach a desired level of anesthesia and may reduce the arterial hypotension. Heart rhythm is remarkably stable.

With controlled ventilation and normal PaCO, cardiac output is maintained despite increasing depth of anesthesia.

Muscle relaxation is often adequate for intra-abdominal operations at normal levels of anesthesia. Complete muscle paralysis can be attained with small doses of muscle relaxants. All commonly used muscle relaxants are markedly potentiated with isoflurane, the effect being most profound with the nondepolarizing type. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of Isoflurane. All commonly used muscle relaxants are compatible with Isoflurane.

Isoflurane can produce coronary vasodilation.

Pharmacokinetics:

Isoflurane undergoes minimal biotransformation in man. In the post anesthesia period, only 0.17% of the Isoflurane taken up can be recovered as urinary metabolites.

Indications & Usage:

Isoflurane may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia

Contraindications:

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

Warnings and precautions:

– 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 appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases myoglobinuria. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.

– Malignant Hyperthermia includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and unstable blood pressure. Treatment includes discontinuance 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.

– 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.

– Isoflurane 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.

– maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease.

– isoflurane can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide, which may result in elevated levels of carboxyhemoglobin in some patients.

– Isoflurane may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics

– Isoflurane may cause a slight decrease in intellectual function for 2 or 3 days following anesthesia. Small changes in moods and symptoms may persist for up to 6 days after administration.

Drug Interactions:

Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably non-depolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N₂O.

Use in Pregnancy and lactation:

Pregnancy Category C: fetotoxic effect in mice: 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 Mothers: It 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

Adverse Reactions:

Adverse reactions include respiratory depression, hypotension and arrhythmias. Shivering, nausea, vomiting and ileus have been observed in the postoperative period, transient elevations in white blood count have been observed , 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 and perioperative hyperkalemia

There have been rare post-marketing reports of hepatic failure and hepatic necrosis.

Overdosage:

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.

Dosage and Administration:

Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by Isoflurane  and the heart rate tends to be increased. The use of anticholinergic drugs is a matter of choice.

The concentration of Isoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using Vaporizers calibrated specifically for Isoflurane.

Induction 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. Surgical 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.

Packaging:

Each one unit carton package contains 100 or 250 ml amber glass bottle

Storage:

Store at room temperature 15°-30°C in well closed container