Brevital Sodium (Methohexital Sodium for Injection)

Brevital Sodium can be used in adults as follows:

1. For intravenous induction of anesthesia prior to the use of other general anesthetic agents.
2. For intravenous induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for short surgical procedures; Brevital may be given by infusion or intermittent injection.
3. For use along with other parenteral agents, usually narcotic analgesics, to supplement subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for longer surgical procedures.
4. As intravenous anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli.
5. As an agent for inducing a hypnotic state.

Brevital can be used in pediatric patients older than 1 month as follows:

1. For rectal or intramuscular induction of anesthesia prior to the use of other general anesthetic agents.
2. For rectal or intramuscular induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents for short surgical procedures.
3. As rectal or intramuscular anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli.

WARNING

Brevital should be used only in hospital or ambulatory care settings that provide forcontinuous monitoring of respiratory (e.g. pulse oximetry) and cardiac function. Immediate availability of resuscitative drugs and age-and size-appropriate equipment for bag/valve/mask ventilation and intubation and personnel trained in their use and skilled in airway management should be assured. For deeply sedated patients, a designated individual other than the practitioner performing the procedure should be present to continuously monitor the patient.

Side effects associated with Brevital are extensions of pharmacologic effects and include:

Cardiovascular

• Circulatory depression,
• thrombophlebitis,
• hypotension,
• tachycardia,
• peripheral vascular collapse, and
• convulsions in association with cardiorespiratory arrest

Respiratory

• Respiratory depression (including apnea),
• cardiorespiratory arrest,
• laryngospasm,
• bronchospasm,
• hiccups, and
• dyspnea

Neurologic

• Skeletal muscle hyperactivity (twitching),
• injury to nerves adjacent to injection site, and
• seizures

Psychiatric

• Emergence delirium, restlessness, and anxiety may occur, especially in the presence of postoperative pain

Gastrointestinal

• Nausea, emesis, abdominal pain, and liver function tests abnormal

Allergic

• Erythema, pruritus, urticaria, and cases of anaphylaxis have been reported rarely

Other

Other adverse reactions include

• pain at injection site,
• salivation,
• headache, and
• rhinitis

For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 (1-800-332-1088) or ww.fda.gov/medwatch/.

Drug Abuse And Dependence

Controlled Substance - Brevital is a Schedule IV drug.

Brevital may be habit-forming.

Facilities for assisting ventilation and administering oxygen are necessary adjuncts for all routes of administration of anesthesia. Since cardiorespiratory arrest may occur, patients should be observed carefully during and after use of Brevital. Age-and size-appropriate resuscitative equipment (i.e., intubation and cardioversion equipment, oxygen, suction, and a secure intravenous line) and personnel qualified in its use must be immediately available.

Preanesthetic medication is generally advisable. Brevital may be used with any of the recognized preanesthetic medications.

Preparation Of Solution

• FOLLOW DILUTION INSTRUCTIONS EXACTLY.
• Freshly prepare solutions of Brevital and use promptly. Reconstituted solutions of Brevital are chemically stable at room temperature for 24 hours.

Diluents

• ONLY USE BACTERIOSTATIC-FREE DILUENT – Recommended diluents are based on route of administration (see Dilution Instructions).
• Incompatible diluents: Lactated Ringer’s Injection

Dilution Instructions

• 1% solutions (10 mg/mL) should be prepared for intermittent intravenous and rectal administration; 0.2% solutions (2 mg/mL) should be prepared for continuous intravenous drug administration; 5% solutions (50 mg/mL) should be prepared for intramuscular administration.
• Contents of vials should be diluted as follows.

For Intermitient Intravenous And Rectal Administration

The preferred diluent for intermittent intravenous and rectal administration is Sterile Water for Injection. 5% Dextrose Injection, or 0.9% Sodium Chloride Injection are also acceptable diluents.

When the first dilution is made with the 2.5 g, the solution in the vial will be yellow. When further diluted to make a 1% solution, it must be clear and colorless or should not be used.

For Continuous Intravenous Administration

For continuous drip anesthesia, prepare a 0.2% solution by adding 500 mg of Brevital Sodium to 250 mL of diluent. For this dilution, either 5% glucose solution or isotonic (0.9%) sodium chloride solution ONLY is recommended as the diluent instead of sterile water for injection in order to avoid extreme hypotonicity.

For Intramuscular Administration

The preferred diluent for intramuscular administration is Sterile Water for Injection. 0.9% Sodium Chloride Injection is also an acceptable diluent.

Administration

Dosage is highly individualized; the drug should be administered only by those completely familiar with its quantitative differences from other barbiturate anesthetics.

Adults

Brevital Sodium is administered intravenously in a concentration of no higher than 1%. Higher concentrations markedly increase the incidence of muscular movements and irregularities in respiration and blood pressure.

Induction of anesthesia

For induction of anesthesia, a 1% solution is administered at a rate of about 1 mL/5 seconds. Gaseous anesthetics and/or skeletal muscle relaxants may be administered concomitantly. The dose required for induction may range from 50 to 120 mg or more but averages about 70 mg. The usual dosage in adults ranges from 1 to 1.5 mg/kg. The induction dose usually provides anesthesia for 5 to 7 minutes.

Maintenance of anesthesia

Maintenance of anesthesia may be accomplished by intermittent injections of the 1% solution or, more easily, by continuous intravenous drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 mL of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/minute (1 drop/second). The rate of flow must be individualized for each patient. For longer surgical procedures, gradual reduction in the rate of administration is recommended. Other parenteral agents, usually narcotic analgesics, are ordinarily employed along with Brevital during longer procedures.

Pediatric Patients

Brevital is administered intramuscularly in a 5% concentration and administered rectally as a 1% solution.

Induction of anesthesia

For the induction of anesthesia by the intramuscular route of administration, the usual dose ranges from 6.6 to 10 mg/kg of the 5% concentration. For rectal administration, the usual dose for induction is 25 mg/kg using the 1% solution.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Compatibility Information

Solutions of Brevital should not be mixed in the same syringe or administered simultaneously during intravenous infusion through the same needle with acid solutions, such as atropine sulfate, metocurine iodide, and succinylcholine chloride. Alteration of pH may cause free barbituric acid to be precipitated. Solubility of the soluble sodium salts of barbiturates, including Brevital Sodium, is maintained only at a relatively high (basic) pH.

Because of numerous requests from anesthesiologists for information regarding the chemical compatibility of these mixtures, the following chart contains information obtained from compatibility studies in which a 1% solution of Brevital was mixed with therapeutic amounts of agents whose solutions have a low (acid) pH.

• Prior chronic administration of barbiturates or phenytoin (e.g. for seizure disorder) appears to reduce the effectiveness of Brevital.
• Barbiturates may influence the metabolism of other concomitantly used drugs, such as
  • phenytoin,
  • halothane,
  • anticoagulants,
  • corticosteroids,
  • ethyl alcohol, and
  • propylene glycol-containing solutions.

• There are no adequate and well-controlled studies in pregnant women.
• Brevital has been used in cesarean section delivery but, because of its solubility and lack of protein binding, it readily and rapidly traverses the placenta.
• Caution should be exercised when Brevital is administered to a nursing woman.