"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
In susceptible individuals, potent inhalation anesthetic agents may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. In genetically susceptible pigs, SUPRANE (desflurane) induced malignant hyperthermia. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia: acute hypoxia, hypercapnia, and hypovolemia.
Treatment of malignant hyperthermia includes discontinuation of triggering agents, administration of intravenous dantrolene sodium, and application of supportive therapy. (Consult prescribing information for dantrolene sodium intravenous for additional information on patient management.) Renal failure may appear later, and urine flow should be monitored and sustained if possible.
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. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Respiratory Adverse Reactions in Pediatric Patients
SUPRANE (desflurane) is not recommended for induction of general anesthesia via mask in children due to a high incidence of moderate to severe respiratory adverse reactions, including laryngospasm, coughing, breathholding, and secretion seen in clinical studies [see Clinical Studies].
SUPRANE (desflurane) is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [see Clinical Studies]. Caution should be exercised when SUPRANE (desflurane) is used for maintenance anesthesia with laryngeal mask airway (LMA) in children 6 years old or younger because of the increased potential for adverse respiratory events, e.g. coughing and laryngospasm, especially with removal of the LMA under deep anesthesia [see Pediatric Use].
Interactions with Desiccated Carbon Dioxide Absorbents
Desflurane, like some other inhalation anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide that may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of SUPRANE (desflurane) .
With the use of halogenated anesthetics, disruption of hepatic function, icterus and fatal liver necrosis have been reported; such reactions appear to indicate hypersensitivity. As with other halogenated anesthetic agents, SUPRANE (desflurane) may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics [see CONTRAINDICATIONS]. Cirrhosis, viral hepatitis or other pre-existing hepatic disease may be a reason to select an anesthetic other than a halogenated anesthetic. As with all halogenated anesthetics, repeated anesthesia within a short period of time should be approached with caution.
Transient elevations in glucose and white blood cell count may occur as with use of other anesthetic agents.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Animal carcinogenicity studies have not been performed with SUPRANE (desflurane) . In vitro and in vivo genotoxicity studies did not demonstrate mutagenicity or chromosomal damage by SUPRANE (desflurane) . Tests for genotoxicity included the Ames mutation assay, the metaphase analysis of human lymphocytes, and the mouse micronucleus assay.
Fertility was not affected after 1 MAC-Hour per day exposure (cumulative 63 and 14 MAC-Hours for males and females, respectively). At higher doses, parental toxicity (mortalities and reduced weight gain) was observed which could affect fertility.
Use In Specific Populations
Pregnancy Category B.There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies have been performed in rats at doses up to at 1 MAC hour for a minimum of 21 days and have revealed no evidence of impaired fertility or harm to the fetus due to SUPRANE (desflurane) .
No teratogenic effect was observed at approximately 10 and 13 cumulative MAC-Hour exposures at 1 MAC-Hour per day during organogenesis in rats or rabbits. At higher doses increased incidences of post-implantation loss and maternal toxicity were observed. However, at 10 MAC-Hours cumulative exposure in rats, about 6% decrease in the weight of male pups was observed at preterm caesarean delivery.
Rats exposed to SUPRANE (desflurane) at 1 MAC-Hour per day from gestation day 15 to lactation day 21, did not show signs of dystocia. Body weights of pups delivered by these dams at birth and during lactation were comparable to that of control pups. No treatment related behavioral changes were reported in these pups during lactation.
Labor and Delivery
The safety of SUPRANE (desflurane) during labor or delivery has not been demonstrated. SUPRANE (desflurane) is a uterine-relaxant.
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 SUPRANE (desflurane) is administered to a nursing woman.
Respiratory Adverse Reactions in Pediatric Patients
SUPRANE (desflurane) is approved for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE (desflurane) , and tracheal intubation.
SUPRANE (desflurane) is not recommended for induction of general anesthesia via mask in children because of the high incidence of moderate to severe respiratory adverse reactions, including laryngospasm (50%), coughing (72%), breathholding (68%), increase in secretions (21%) and oxyhemoglobin desaturation (SpO2 < 90%) (26%) seen in clinical studies [see Clinical Studies].
SUPRANE (desflurane) is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [see Clinical Studies]. Caution should be exercised when SUPRANE (desflurane) is used for maintenance anesthesia with laryngeal mask airway (LMA) in children 6 years old or younger because of the increased potential for adverse respiratory events, e.g. coughing and laryngospasm, especially with removal of the LMA under deep anesthesia [see WARNINGS AND PRECAUTIONS].
The minimum alveolar concentration (MAC) of SUPRANE (desflurane) decreases with increasing patient age. The dose should be adjusted accordingly. The average MAC for SUPRANE (desflurane) in a 70 year old patient is two-thirds the MAC for a 20 year old patient [see DOSAGE AND ADMINISTRATION, Table 1 and Clinical Studies].
Concentrations of 1-4% SUPRANE (desflurane) in nitrous oxide/oxygen have been used in patients with chronic renal or hepatic impairment and during renal transplantation surgery. Because of minimal metabolism, a need for dose adjustment in patients with renal and hepatic impairment is not to be expected.
Nine patients receiving SUPRANE (desflurane) (N=9) were compared to 9 patients receiving isoflurane, all with chronic renal insufficiency (serum creatinine 1.5-6.9 mg/dL). No differences in hematological or biochemical tests, including renal function evaluation, were seen between the two groups. Similarly, no differences were found in a comparison of patients receiving either SUPRANE (desflurane) (N=28) or isoflurane (N=30) undergoing renal transplant.
Eight patients receiving SUPRANE (desflurane) were compared to six patients receiving isoflurane, all with chronic hepatic disease (viral hepatitis, alcoholic hepatitis, or cirrhosis). No differences in hematological or biochemical tests, including hepatic enzymes and hepatic function evaluation, were seen.
Last reviewed on RxList: 4/27/2010
This monograph has been modified to include the generic and brand name in many instances.
Additional Suprane Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.