Suprane

Name: Suprane

Uses of Suprane

Suprane is a prescription medication used to prevent or reduce pain during surgery.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Suprane Drug Class

Suprane is part of the drug class:

  • Halogenated hydrocarbons

Side Effects of Suprane

Serious side effects have been reported with Suprane.

Common side effects of Suprane include

  • coughing
  • breath holding
  • apnea (a disorder that causes your breathing to stop or get very shallow)
  • nausea
  • vomiting

This is not a complete list of Suprane side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses For Suprane

Desflurane belongs to the group of medicines known as general anesthetics. Inhaled desflurane is used to cause general anesthesia (loss of consciousness) before and during surgery in adults. It is also used as a maintenance anesthesia in adults and children after receiving other anesthetics before and during surgery.

This medicine is to be given only by or under the direct supervision of a trained doctor .

Precautions While Using Suprane

Your doctor will check you closely after receiving this medicine. This will allow your doctor to see if the medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Hyperkalemia may occur rarely after receiving this medicine. Tell your doctor right away if you have confusion, irregular heartbeat, nausea or vomiting, numbness or tingling in the hands, feet, or legs, or trouble breathing after receiving this medicine.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

For patients going home within 24 hours after receiving a general anesthetic:

  • General anesthetics may cause some people to feel drowsy, tired, or weak for a while after they have been given. They may also cause problems with coordination and one's ability to think. Therefore, for about 24 hours (or longer if necessary) after receiving a general anesthetic, do not drive, use machines, or do anything else that could be dangerous if you are not alert.
  • Unless otherwise directed by your doctor or dentist, do not drink alcoholic beverages or take other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness) for about 24 hours after you have received a general anesthetic. To do so may add to the effects of the anesthetic. Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds, other sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures or barbiturates, and muscle relaxants.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Contraindications

The use of Suprane is contraindicated in the following conditions:

• Known or suspected genetic susceptibility to malignant hyperthermia. • Patients in whom general anesthesia is contraindicated. • Induction of anesthesia in pediatric patients. • Patients with known sensitivity to Suprane or to other halogenated agents [See Warnings and Precautions (5.5)]. • Patients with a history of moderate to severe hepatic dysfunction following anesthesia with Suprane or other halogenated agents and not otherwise explained [See Warnings and Precautions (5.5)].

Drug Interactions

No clinically significant adverse interactions with commonly used preanesthetic drugs, or drugs used during anesthesia (muscle relaxants, intravenous agents, and local anesthetic agents) were reported in clinical trials. The effect of Suprane on the disposition of other drugs has not been determined. Similar to isoflurane, Suprane does not predispose to premature ventricular arrhythmias in the presence of exogenously infused epinephrine in swine.

Benzodiazepines and Opioids (MAC Reduction)

Benzodiazepines and opioids decrease the amount of desflurane (MAC) needed to produce anesthesia. This effect is shown in Table 3 for intravenous midazolam (25-50 µg/kg) and intravenous fentanyl (3-6 µg/kg) in patients of two different age groups.

Table 3

Suprane MAC with Fentanyl or Midazolam Mean ± SD (percent reduction)

Dose

18-30 years

31-65 years

No fentanyl

6.4 ± 0.0

6.3 ± 0.4

3 µg/kg fentanyl

3.5 ± 1.9 (46%)

3.1 ± 0.6 (51%)

6 µg/kg fentanyl

3.0 ± 1.2 (53%)

2.3 ± 1.0 (64%)

No midazolam

6.9 ± 0.1

5.9 ± 0.6

25 µg/kg midazolam

-

4.9 ± 0.9 (16%)

50 µg/kg midazolam

-

4.9 ± 0.5 (17%)

Neuromuscular Blocking Agents

Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED95 of succinylcholine by approximately 30% and that of atracurium and pancuronium by approximately 50% compared to N2O/opioid anesthesia (see Table 4). The effect of desflurane on duration of nondepolarizing neuromuscular blockade has not been studied.

Table 4

Dosage of Muscle Relaxant Causing 95% Depression in Neuromuscular Blockade


Desflurane Concentration

Mean ED95 (µg/kg)

Pancuronium

Atracurium

Succinylcholine

Vecuronium

0.65 MAC 60% N2O/O2

26

133

-

-

1.25 MAC 60% N2O/O2

18

119

-

-

1.25 MAC O2

22

120

360

19

 

Dosage reduction of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation, because potentiation of neuromuscular blocking agents requires equilibration of muscle with the delivered partial pressure of Suprane.

Among nondepolarizing drugs, pancuronium, atracurium, and vecuronium interactions have been studied. In the absence of specific guidelines:

1. For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants or succinylcholine. 2. During maintenance of anesthesia, the dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.

Concomitant use with N2O

Concomitant administration of N2O reduces the MAC of Suprane [See Dosage and Administration (2), Table 1].

Use in specific populations

Pregnancy

Risk Summary

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, embryo-fetal toxicity (reduced viable fetuses and/or increased post-implantation loss) was noted in pregnant rats and rabbits administered 1 MAC desflurane for 4 hours a day (4 MAC-hours/day) during organogenesis.

Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [See Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%, respectively.

Clinical Considerations

Labor or Delivery

The safety of Suprane during labor or delivery has not been demonstrated. Suprane is a uterine-relaxant.

Data

Animal Data

Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 4.0 hours (0.5, 1.0, or 4.0 MAC-hours) per day during organogenesis (Gestation Day 6-15).

Embryo-fetal toxicity (increased post-implantation loss and reduced viable fetuses) was noted in the 4 hour treatment group in the presence of maternal toxicity (reduced body weight gain). There was no evidence of malformations in any group.

Pregnant rabbits were exposed to 8.9% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 3.0 hours per day during organogenesis (Gestation Days 6-18). Fetal toxicity (reduced viable fetuses) was noted in the 3 hour treatment group in the presence of maternal toxicity (reduced body weight). There was no evidence of malformations in any group.

Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 4.0 hours per day from late gestation and through lactation (Gestation Day 15 to Lactation Day 21). Pup body weights were reduced in the 4 hours per day group in the presence of maternal toxicity (increased mortality and reduced body weight gain). This study did not evaluate neurobehavioral function including learning and memory or reproductive behavior in the first generation (F1) pups.

In a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on Gestation Day 122 increased neuronal apoptosis in the developing brain of the fetus. In other published studies, administration of either isoflurane or propofol for 5 hours on Gestation Day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. With respect to brain development, this time period corresponds to the third trimester of gestation in the human. The clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits [See Warnings and Precautions (5.6), Use in Specific Populations (8.4), and Nonclinical Toxicology (13.2)].

Lactation

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 is administered to a nursing woman.

Pediatric Use

Respiratory Adverse Reactions in Pediatric Patients

Suprane is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than Suprane, and tracheal intubation.

Is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing (26%), laryngospasm (13%) and secretions (12%) [See Clinical Studies (14.5)].

Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of Suprane delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [See Clinical Studies (14.5)].  Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly.

When Suprane is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly.

Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as Suprane, 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. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans.

In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss. Data from isoflurane-treated rodents and ketamine-treated primates suggest that the neuronal and oligodendrocyte cell losses are associated with prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data [See Warnings and Precautions (5.6), Use in Specific Populations (8.1), and Nonclinical Toxicology (13.2)].

Geriatric Use

The minimum alveolar concentration (MAC) of Suprane decreases with increasing patient age. The dose should be adjusted accordingly. The average MAC for Suprane in a 70 year old patient is two-thirds the MAC for a 20 year old patient [See Dosage and Administration (2) Table 1 and Clinical Studies (14.3)].

Renal Impairment

Concentrations of 1-4% Suprane 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 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 desflurane (N=28) or isoflurane (N=30) undergoing renal transplant.

Hepatic Impairment

Eight patients receiving Suprane 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.

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