Isoflurane Liquid Inhalation_

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 USP, a general anesthetic, is an inhalation agent indicated for induction and maintenance of general anesthesia. ( 1 )

• Isoflurane USP should be administered only by persons trained in the administration of general anesthesia
• Isoflurane USP should only be delivered using a vaporizer specifically designed and designated for use with isoflurane. • The administration of general anesthesia must be individualized and titrated based on the patient’s age and clinical status
• Important Dosage and Administration Information 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
• Isoflurane is administered by inhalation
• Isoflurane should be delivered from a vaporizer specifically designed for use with isoflurane
• Dosage for induction and maintenance must be individualized and titrated to the desired effect according to the patient’s age and clinical status
• With the exception of
• Neonates, the minimum alveolar concentration (MAC) of isoflurane decreases with increasing patient age
• Nitrous oxide decreases the MAC of isoflurane (see Table 1 )
• Opioids decrease the MAC of isoflurane [see Drug Interactions ]
• Isoflurane potentiates the muscle relaxant effect of all neuromuscular blockers and decreases the required doses of neuromuscular blocking agents [see Drug Interactions ]
• The dose should be adjusted accordingly. …

3. DOSAGE FORMS AND STRENGTHS Isoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers, 100% isoflurane. Liquid (stable): 100% ( 3 )

• During the induction of anesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of larynogospasm, particularly in children
• Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as Isoflurane USP, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. …

The minimum alveolar concentration (MAC) of isoflurane decreases with increasing patient age. The dose should be adjusted accordingly [see Dosage and Administration (2.4) ].

Isoflurane USP is contraindicated in patients: • in whom general anesthesia is contraindicated. • with known sensitivity to Isoflurane USP or to other halogenated agents [see Warnings and Precautions ( 5.3 )]. • with known or suspected genetic susceptibility to malignant hyperthermia [see Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.5 )]. …

• Concomitant use of N 2 O and/or opioids reduces the MAC of Isoflurane USP. Adjust dose accordingly. ( 7.1 , 7.2 ) • Isoflurane USP decreases the doses of neuromuscular blocking agents required. Adjust dose accordingly. ( 7.3 ) 7.1 Opioids Opioids decrease the Minimum Alveolar Concentration (MAC) of isoflurane. Opioids such as fentanyl and its analogues, when combined with isoflurane, may lead to a synergistic fall in blood pressure and respiratory rate. 7.2 Nitrous Oxide Nitrous oxide decreases the MAC of isoflurane [see Dosage and Administration (2.1) ]. …

• Malignant Hyperthermia : Malignant hyperthermia may occur, especially in individuals with known or suspected susceptibility based on genetic factors or family history. Discontinue triggering agents, administer intravenous dantrolene sodium, and apply supportive therapies. ( 5.1 ) • Perioperative Hyperkalemia : Perioperative hyperkalemia may occur. Patients with latent or overt neuromuscular disease, particularly with Duchenne muscular dystrophy, appear to be most vulnerable. Early, aggressive intervention is recommended. ( 5.2 ) • Hepatic Reactions : May cause sensitivity hepatitis in patients sensitized by previous exposure to halogenated anesthetics. …

Most common adverse reactions (incidence > 5%) are agitation, cough, breath holding, nausea, chills/shivering, vomiting, laryngospasm, delirium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Piramal Critical Care, Inc. at 1-888-822-8431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The following adverse reactions were identified from controlled clinical trials of adult and pediatric subjects exposed to Isoflurane USP. The trials were conducted using a variety of pre-medications, other anesthetics, and surgical procedures of varying lengths. …

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased livebirth index) during organogenesis. …

The symptoms of overdosage of Isoflurane USP can present as a deepening of anesthesia, cardiac and/or respiratory depression in spontaneously breathing patients, and cardiac depression in ventilated patients in whom hypercapnia and hypoxia may occur only at a late stage. In the event of overdosage, or what may appear to be overdosage, the following action should be taken, as appropriate: Stop drug administration, establish a clear airway, and initiate assisted or controlled ventilation with pure oxygen. …

16.1 Safety and Handling Occupational Caution The following reactions have been reported following occupational exposure to isoflurane: dyspnea, bronchospasm, stridor, cough, dizziness, paresthesia, hepatic reactions, flushing rash, contact dermatiti …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.