Forane Solution for Inhalation

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

Each ml inhalation liquid contains Isoflurane USP 100% v/v.

Isoflurane is a nonflammable liquid and a general inhalation anesthetic drug. Induction of and recovery from Isoflurane anesthesia are rapid. Isoflurane has a mild pungency which limits the rate of induction, although excessive salivation or tracheobronchial secretions do not appear to be stimulated. Pharyngeal and laryngeal reflexes are readily obtunded. Isoflurane is a profound respiratory depressant. As anesthetic dose is increased, tidal volume decreases and respiratory rate is unchanged. This depression is partially reversed by surgical stimulation, even at deeper levels of anesthesia. Isoflurane evokes a sigh response reminiscent of that seen with diethyl ether and enflurane, although the frequency is less than with enflurane. Blood pressure decreases with induction of anesthesia but returns toward normal with surgical stimulation. Progressive increases in depth of anesthesia produce corresponding decreases in blood pressure. Nitrous oxide diminishes the inspiratory concentration of isoflurane required to reach a desired level of anesthesia and may reduce the arterial hypotension seen with isoflurane alone. With controlled ventilation and normal PaC0₂, cardiac output is maintained despite increasing depth of anesthesia, primarily through an increase in heart rate which compensates for a reduction in stroke volume. The hypercapnia which attends spontaneous ventilation during isoflurane anesthesia further increases heart rate and raises cardiac output above awake levels. 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.

Route of administration: It should be administered by inhalation delivered from a vaporizer specifically designed for use with isoflurane. Isoflurane should be administered only by persons trained in the administration of general anesthesia. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and circulatory resuscitation must be immediately available. The minimum alveolar concentration (MAC) of isoflurane decreases with increasing patient age.

Premedication: 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.

Induction: Induction with isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, laryngospasm and bronchospasm, which increases with the concentration of isoflurane. 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.

Drug interaction with medication: Opioids decrease the MAC of Forane. Opioids such as fentanyl and its analogues, when combined with Forane, may lead to a synergistic fall in blood pressure and respiratory rate. Nitrous oxide decreases the MAC of Forane. Forane potentiates the muscle relaxant effect of all muscle relaxants and decreases the required doses of neuromuscular blocking agents. In general, anesthetic concentrations of Forane at equilibrium reduce the ED95 of succinylcholine, atracurium, pancuronium, rocuronium and vecuronium. Forane may lead to marked hypotension in patients treated with calcium antagonists. Concomitant use of beta blockers may exaggerate the cardiovascular effects of inhalational anesthetics, including hypotension and negative inotropic effects. Concomitant use of MAO inhibitors and inhalational anesthetics may increase the risk of hemodynamic instability during surgery or medical procedures.

Isoflurane is contraindicated in patients with known hypersensitivity to isoflurane or other halogenated agents or any other components of this product. It is also contraindicated in whom general anesthesia is contraindicated, in patients with known or suspected genetic susceptibility to malignant hyperthermia, with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics.

The most common side effects are delirium, agitation, breath holding, cough, laryngospasm, nausea, vomiting, chills/shivering and nodal arrhythmia.

There are no adequate and well-controlled studies in pregnant women. Due to insufficient information regarding the excretion of isoflurane in human milk, the potential risks and benefits for each specific patient should be carefully considered before isoflurane is administered to nursing women.

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. In susceptible individuals, may trigger malignant hyperthermia, a skeletal muscle hypermetabolic state leading to high oxygen demand. If malignant hyperthermia is suspected, discontinue all triggering agents, administer intravenous dantrolene sodium and initiate supportive therapies. Cases of mild, moderate and severe postoperative hepatic dysfunction or hepatitis with or without jaundice, including fatal hepatic necrosis and hepatic failure, have been reported with Forane. QTc prolongation, with rare instances of torsade de pointes, have been reported. Monitor QT interval when administering Forane to susceptible patients. All patients anesthetized with Forane should be continually monitored. Respiration should be closely monitored and assisted or controlled ventilation employed when necessary. Maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease. Consider additional cardiac monitoring in patients with known coronary artery disease, as clinically necessary. Particular care must be taken when selecting the dosage for patients who are hypovolemic, hypotensive or otherwise hemodynamically compromised, e.g., due to concomitant medications. In patients with or at risk for elevations of intracranial pressure (ICP), administer Forane in conjunction with ICP reducing strategies, as clinically appropriate. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of Forane. Forane, as well as other general anesthetics, may cause a slight decrease in intellectual function for 2 or 3 days following anesthesia.

Use in children and adolescents: Studies conducted in young children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Decisions regarding the timing of any elective procedures requiring anesthesia in pediatric patients should take into consideration the benefits of the procedure weighed against the potential risks.

In the event of overdose, stop drug administration, establish a clear airway and initiate assisted or controlled ventilation with pure oxygen. Monitor cardiovascular function and manage signs of poor end-organ perfusion as clinically indicated.

General (Inhalation) anesthetics

Store below 25°C in a dry place, protected from light. Keep away from the reach of children.