Methohexital

Jump to: navigation, search
Methohexital
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Black Box Warning

Warning
See full prescribing information for complete Boxed Warning.
  • Brevital should be used only in hospital or ambulatory care settings that provide for continuous 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. (See Warnings)

Overview

Methohexital is a general anesthetic that is FDA approved for the {{{indicationType}}} of anesthesia. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cardiovascular: hypotension, dermatologic: injection site pain, musculoskeletal: spasmodic movement, respiratory: cough, hiccoughs, laryngeal spasm.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Anesthesia: induction, 1 to 1.5 mg/kg (50 to 120 mg, mean 70 mg) IV administered at a rate of 1 mL every 5 seconds (1% solution), which usually provides anesthesia for 5 to 7 minutes; gaseous anesthetics and skeletal muscle relaxants may be administered concomitantly [2]
  • Anesthesia: maintenance, intermittent IV injections of 20 to 40 mg (2 to 4 mL of a 1% solution) as required, usually every 4 to 7 minutes OR by continuous IV drip of 3 mL/min (0.2% solution); individualize flow rate for each patient; for longer surgical procedures, gradual reduction in the administration rate is recommended.
  • Procedural sedation: 0.75 to 1 mg/kg IV; can be re-dosed 0.5 mg/kg every 2-5 min as needed

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

  • Procedural sedation.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Methohexital in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

  • Anesthesia: (older than 1 month) 6.6 to 10 mg/kg IM (5% solution) OR 25 mg/kg RECTALLY (1% solution).
  • Procedural sedation: 25 mg/kg rectally as 1% solution.
  • Procedural sedation: 0.5 to 1 mg/kg IV.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

  • Procedural sedation

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Methohexital in pediatric patients.

Contraindications

  • Brevital Sodium is contraindicated in patients in whom general anesthesia is contraindicated, in those with latent or manifest porphyria, or in patients with a known hypersensitivity to barbiturates.

Warnings

Warning
See full prescribing information for complete Boxed Warning.
  • Brevital should be used only in hospital or ambulatory care settings that provide for continuous 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. (See Warnings)
See Boxed Warning
  • As with all potent anesthetic agents and adjuncts, Brevital should be used only in hospital or ambulatory care settings that provide for continuous 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.
  • Maintenance of a patent airway and adequacy of ventilation must be ensured during induction and maintenance of anesthesia with methohexital sodium solution. Laryngospasm is common during induction with all barbiturates and may be due to a combination of secretions and accentuated reflexes following induction or may result from painful stimuli during light anesthesia. Apnea/hypoventilation may be noted during induction, which may impair pulmonary ventilation; the duration of apnea may be longer than that produced by other barbiturate anesthetics. Cardiorespiratory arrest may occur.
  • This prescribing information describes intravenous use of methohexital sodium in adults. It also discusses intramuscular and rectal administration in pediatric patients older than one month. Although the published literature discusses intravenous administration in pediatric patients, the safety and effectiveness of intravenous administration of methohexital sodium in pediatric patients have not been established in well-controlled, prospective studies. (See Precautions— Pediatric Use)
  • Seizures may be elicited in subjects with a previous history of convulsive activity, especially partial seizure disorders.
  • Because the liver is involved in demethylation and oxidation of methohexital and because barbiturates may enhance preexisting circulatory depression, severe hepatic dysfunction, severe cardiovascular instability, or a shock-like condition may be reason for selecting another induction agent.
  • Prolonged administration may result in cumulative effects, including extended somnolence, protracted unconsciousness, and respiratory and cardiovascular depression. Respiratory depression in the presence of an impaired airway may lead to hypoxia, cardiac arrest, and death.
  • The CNS-depressant effect of Brevital Sodium may be additive with that of other CNS depressants, including ethyl alcohol and propylene glycol.

Adverse Reactions

Clinical Trials Experience

  • Side effects associated with Brevital Sodium are extensions of pharmacologic effects and include:
Cardiovascular
Respiratory
Neurologic
  • Skeletal muscle hyperactivity (twitching), injury to nerves adjacent to injection site, and seizures
Psychiatric
Gastrointestinal
Allergic
Other
  • For medical advice about adverse reactions contact your medical professional. To report suspected adverse reactions, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or http://www.fda.gov/medwatch/.

Postmarketing Experience

There is limited information regarding Methohexital Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Methohexital Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B There is no FDA guidance on usage of Methohexital in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methohexital in women who are pregnant.

Labor and Delivery

  • Brevital Sodium has been used in cesarean section delivery but, because of its solubility and lack of protein binding, it readily and rapidly traverses the placenta.

Nursing Mothers

  • Caution should be exercised when Brevital Sodium is administered to a nursing woman.

Pediatric Use

  • The safety and effectiveness of methohexital sodium in pediatric patients below the age of 1 month have not been established. Seizures may be elicited in subjects with a previous history of convulsive activity, especially partial seizure disorders. Apnea has been reported following dosing with methohexital regardless of the route of administration used. Studies using methohexital sodium intravenously in pediatric patients have been reported in the published literature. This literature is not adequate to establish the safety and effectiveness of intravenous administration of methohexital sodium in pediatric patients. Due to a variety of limitations such as study design, biopharmaceutic issues, and the wide range of effects observed with similar doses of intravenous methohexital, additional studies of intravenous methohexital in pediatric patients are necessary before this route can be recommended in pediatric patients. (See Warnings)

Geriatic Use

  • Clinical studies of Brevital did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Elderly subjects may commonly have conditions in which methohexital should be used cautiously such as obstructive pulmonary disease, severe hypertension or hypotension, preexisting circulatory depression, myocardial disease, congestive heart failure, or severe anemia. Caution should be exercised in debilitated patients or in those with impaired function of respiratory, circulatory, renal, hepatic, or endocrine systems (see Warnings, precautions and adverse reactions). Barbiturates may influence the metabolism of other concomitantly used drugs that are commonly taken by the elderly, such as anticoagulants and corticosteroids. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see Precautions-Drug Interactions).

Gender

There is no FDA guidance on the use of Methohexital with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methohexital with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methohexital in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methohexital in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methohexital in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methohexital in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Methohexital Administration in the drug label.

Monitoring

There is limited information regarding Methohexital Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Methohexital and IV administrations.

Overdosage

Signs and Symptoms=
  • The onset of toxicity following an overdose of intravenously administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include central nervous system depression, respiratory depression, hypotension, loss of peripheral vascular resistance, and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur.
Treatment
  • To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
  • Establish an airway and ensure oxygenation and ventilation. Resuscitative measures should be initiated promptly. For hypotension, intravenous fluids should be administered and the patient's legs raised. If desirable increase in blood pressure is not obtained, vasopressor and/or inotropic drugs may be used as dictated by the clinical situation.
  • For convulsions, diazepam intravenously and phenytoin may be required. If the seizures are refractory to diazepam and phenytoin, general anesthesia and paralysis with a neuromuscular blocking agent may be necessary.
  • Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Pharmacology

Methohexital wiki1.svg.png
Methohexital wiki2.png
Methohexital
Systematic (IUPAC) name
5-hex-3-yn-2-yl-1- methyl-5-prop-2-enyl-1, 3-diazinane-2,4,6-trione
Identifiers
CAS number 151-83-7
ATC code N01AF01 N05CA15 (WHO)
PubChem 9034
DrugBank DB00474
Chemical data
Formula C14H18N2O3 
Mol. mass 262.304
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability I.V. ~100%
Rectal ~17%
Metabolism Hepatic
Half life 5.6 ± 2.7 minutes
Excretion ?
Therapeutic considerations
Pregnancy cat.

B (USA)

Legal status

Prescription Only (S4)(AU) Schedule IV

Routes Intravenous, rectal

Mechanism of Action

There is limited information regarding Methohexital Mechanism of Action in the drug label.

Structure

  • Brevital® Sodium (Methohexital Sodium for Injection, USP) is 2,4,6 (1H, 3H, 5H)-Pyrimidinetrione, 1-methyl-5-(1-methyl-2-pentynyl)-5-(2-propenyl)-, (±)-, monosodium salt and has the empirical formula C14H17N2NaO3. Its molecular weight is 284.29.
  • The structural formula is as follows:
This image is provided by the National Library of Medicine.
  • Methohexital sodium is a rapid, ultrashort-acting barbiturate anesthetic. Methohexital sodium for injection is a freeze-dried, sterile, nonpyrogenic mixture of methohexital sodium with 6% anhydrous sodium carbonate added as a buffer. It contains not less than 90% and not more than 110% of the labeled amount of methohexital sodium. It occurs as a white, freeze-dried plug that is freely soluble in water.
  • This product is oxygen sensitive. The pH of the 1% solution is between 10 and 11; the pH of the 0.2% solution in 5% dextrose is between 9.5 and 10.5.
  • Methohexital sodium may be administered by direct intravenous injection or continuous intravenous drip, intramuscular or rectal routes (see Precautions—Pediatric Use). Reconstituting instructions vary depending on the route of administration (see Dosage and Administration).

Pharmacodynamics

  • Compared with thiamylal and thiopental, methohexital is at least twice as potent on a weight basis, and its duration of action is only about half as long. Although the metabolic fate of methohexital in the body is not clear, the drug does not appear to concentrate in fat depots to the extent that other barbiturate anesthetics do. Thus, cumulative effects are fewer and recovery is more rapid with methohexital than with thiobarbiturates. In experimental animals, the drug cannot be detected in the blood 24 hours after administration.
  • Methohexital differs chemically from the established barbiturate anesthetics in that it contains no sulfur. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.
  • Intravenous administration of methohexital results in rapid uptake by the brain (within 30 seconds) and rapid induction of sleep.

Pharmacokinetics

  • Following intramuscular administration to pediatric patients, the onset of sleep occurs in 2 to 10 minutes. A plasma concentration of 3 µg/mL was achieved in pediatric patients 15 minutes after an intramuscular dose (10 mg/kg) of a 5% solution. Following rectal administration to pediatric patients, the onset of sleep occurs in 5 to 15 minutes. Plasma methohexital concentrations achieved following rectal administration tend to increase both with dose and with the use of more dilute solution concentrations when using the same dose. A 25 mg/kg dose of a 1% methohexital solution yielded plasma concentrations of 6.9 to 7.9 µg/mL 15 minutes after dosing. The absolute bioavailability of rectal methohexital sodium is 17%.
  • With single doses, the rate of redistribution determines duration of pharmacologic effect. Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity. Excretion occurs via the kidneys through glomerular filtration.

Nonclinical Toxicology

There is limited information regarding Methohexital Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Methohexital Clinical Studies in the drug label.

How Supplied

  • Store between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.)
Brevital® Sodium Vials1:
The 200 mg vials (with 12 mg of anhydrous sodium carbonate) are available as follows:
NDC 42023-148-10 – Single-Use Vials – Pack of 10
The 500 mg vials (with 30 mg anhydrous sodium carbonate) are available as follows:
NDC 42023-105-01 – Multi-Dose Vial – Pack of 1
The 2.5 g vials (with 150 mg anhydrous sodium carbonate) are available as follows:
NDC 42023-106-01 – Multi-Dose Vial – Pack of 1
In crystalline form.
Rx only
Prescribing Information as of February 2014.
Manufactured and Distributed by:
JHP Pharmaceuticals, LLC
Rochester, MI 48307
3003014G

Storage

There is limited information regarding Methohexital Storage in the drug label.

Images

Drug Images

Package and Label Display Panel

Methohexital label.png
This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

There is limited information regarding Methohexital Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Methohexital interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Methohexital Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Methohexital Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.



Linked-in.jpg