Drug Interactions between fluconazole and sevoflurane

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

The use of sevoflurane is contraindicated in patients with known or suspected susceptibility to malignant hyperthermia.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

The 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. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended; as is subsequent evaluation for latent neuromuscular disease. Caution and close monitoring is recommended when using this agent in these patients.

Studies comparing sevoflurane to isoflurane for maintenance of anesthesia during neurosurgical procedures found no difference between sevoflurane and isoflurane with regard to recovery from anesthesia. In patients at risk for elevations of intracranial pressure (ICP), sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.

In a multicenter study to compare the safety of sevoflurane and isoflurane in patients with mild to moderate hepatic impairment, sevoflurane patients had prolonged terminal disposition of fluoride, as evidenced by longer inorganic fluoride half-life than patients with normal hepatic function. Results of evaluations of laboratory parameters (e.g., ALT, AST, alkaline phosphatase, and total bilirubin, etc.), as well as investigator-reported incidence of adverse events relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. The use of this agent in patients with severe hepatic dysfunction has not been investigated. Clinical judgment should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Limited data are available on the use of oral sevoflurane in patients with renal insufficiency. Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. Caution is advised when using sevoflurane in these patients as the safety has not been fully established.

The use of sevoflurane has been associated with seizures. The majority of cases were in children and young adults, most of whom had no medical history of seizures. Seizures have occurred during, or soon after sevoflurane induction, during emergence, and during post-operative recovery up to a day following anesthesia. Caution and clinical judgment should be exercised when using sevoflurane in patients who may be at risk for seizures.