VA Class:CN301

AHFS Class:

• Barbiturates 28:24.04

Generic Name(s):

• Amobarbital Sodium

Amobarbital sodium is a barbiturate hypnotic.

Amobarbital sodium is used principally as a hypnotic in the short-term treatment of insomnia for periods up to 2 weeks in duration; barbiturates appear to lose their efficacy for sleep induction and maintenance after this period of time. Amobarbital sodium also is used for routine sedation and to relieve anxiety and provide sedation preoperatively.

Amobarbital sodium may be used IV or IM to control status epilepticus or acute seizure episodes resulting from meningitis, poisons, eclampsia, tetanus, or chorea. The drug has also been used parenterally to control acute episodes of agitated behavior in psychoses such as catatonic, negativistic, or manic reactions, but has little value in long-term management of psychoses. Parenteral amobarbital sodium may also be useful in narcoanalysis, narcotherapy, and as a diagnostic aid in schizophrenia.

Reconstitution and Administration

Amobarbital sodium may be administered by deep IM or slow IV injection. Superficial IM or subcutaneous injections may be painful and may produce sterile abscesses or sloughs. No more than 5 mL of reconstituted solution of amobarbital sodium (regardless of concentration) should be injected IM at any one site. IV administration of the drug should usually be reserved for emergency treatment of acute seizure states or acute episodes of psychotic behavior. Only hospitalized patients under close supervision should be given the drug IV. The IV injection rate should not exceed 100 mg/minute (1 mL of a 10% concentration or equivalent) for adults or 60 mg/m² per minute (0.6 mL of a 10% concentration or equivalent) for children. Amobarbital and amobarbital sodium also have been administered orally; however, oral preparations containing the drug alone or in fixed combination with secobarbital sodium no longer are commercially available in the US.

Amobarbital sodium injection usually is administered in a concentration of 100 mg/mL (10%) and is prepared by dissolving 500 mg of sterile powder for injection in 5 mL of sterile water for injection. The ampul should be rotated to facilitate solution and must not be shaken. For IM use, a solution containing 200 mg/mL (20%) may be used. To prepare a 20% solution, 500 mg of the sterile powder for injection should be dissolved in 2.5 mL of sterile water for injection. Consult the manufacturer's labeling for reconstitution directions for preparing other concentrations of the drug.

Dosage

Dosage of amobarbital sodium must be individualized for each patient. Following chronic administration, the drug should be withdrawn slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.

The usual IM hypnotic dose for adults is 65-200 mg. IM doses should not exceed 500 mg. The IM hypnotic dose for children is 2-3 mg/kg.

IV dosage of amobarbital sodium is primarily determined by the patient's reaction to slow administration of the drug. The IV hypnotic or anticonvulsant dose of amobarbital sodium for adults and children older than 6 years of age usually ranges from 65-500 mg and should not exceed 1 g.

Precautions

Amobarbital sodium shares the toxic potentials of the barbiturates, and the usual precautions of barbiturate administration should be observed. (See Cautions in the Barbiturates General Statement 28:24.04.)

IV administered amobarbital sodium may cause respiratory depression, apnea, or hypotension, particularly if the drug is administered too rapidly. The drug must be administered slowly at a rate not greater than 100 mg/minute, and personnel and equipment should be readily available for administration of artificial respiration.

Pediatric Precautions

Safety and efficacy of amobarbital sodium in children younger than 6 years of age have not been established.

FDA warns that repeated or prolonged use of general anesthetics and sedation drugs in children younger than 3 years of age or during the third trimester of pregnancy may affect brain development.750,753 Animal studies in multiple species, including nonhuman primates, have demonstrated that use for longer than 3 hours of anesthetic and sedation drugs that block N -methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity leads to widespread neuronal and oligodendrocyte cell loss and alterations in synaptic morphology and neurogenesis in the brain, resulting in long-term deficits in cognition and behavior.750,751,752,753 Across animal species, vulnerability to these neurodevelopmental changes occurs during the period of rapid brain growth or synaptogenesis; this period is thought to correlate with the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age.750 The clinical relevance of these animal findings to humans is not known.750

While some published evidence suggests that similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life, other studies have found no association between pediatric anesthesia exposure and long-term adverse neurodevelopmental outcomes.750,752 Most studies to date have had substantial limitations, and it is not clear whether the adverse neurodevelopmental outcomes observed in children were related to the drug or to other factors (e.g., surgery, underlying illness).750 There is some clinical evidence that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders;750,751,752 however, further research is needed to fully characterize the effects of exposure to general anesthetics in early life, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).750 For further information, see Cautions: Pediatric Precautions, in the Barbiturates General Statement 28:24.04.

Anesthetic and sedation drugs are an essential component of care for children and pregnant women who require surgery or other procedures that cannot be delayed;750,753 no specific general anesthetic or sedation drug has been shown to be less likely to cause neurocognitive deficits than any other such drug.750 Pending further accumulation of data in humans from well-designed studies, decisions regarding the timing of elective procedures requiring anesthesia should take into consideration both the benefits of the procedure and the potential risks.750 When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should discuss with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.750,753 FDA states that procedures that are considered medically necessary should not be delayed or avoided.750,753

Pregnancy

Pregnancy

Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.750,753 The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs.750 (See Cautions: Pediatric Precautions.)

Pharmacology

Amobarbital shares the actions of the sedative-hypnotic barbiturates. (See Pharmacology in the Barbiturates General Statement 28:24.04.)

Pharmacokinetics

Absorption

Amobarbital is absorbed from the GI tract. Plasma concentrations required for therapeutic effects are unknown. Plasma amobarbital concentrations of greater than 50 mcg/mL usually produce deep coma and are potentially lethal.

Elimination

Following bolus IV administration, plasma concentrations of amobarbital decline in a biphasic manner with a half-life of about 40 minutes for the first phase and 20-25 hours for the second phase, although the second phase half-life has ranged from 14-42 hours in individual patients.

Amobarbital is metabolized by the liver via penultimate oxidation of the 3-methylbutyl substituent to form a tertiary alcohol, hydroxyamobarbital, which is an inactive metabolite. About 40-50% of an oral hypnotic dose of amobarbital is excreted in urine as hydroxyamobarbital and its glucuronide conjugates. Less than 1% of an oral hypnotic dose of the drug is excreted in urine unchanged. Conjugates of hydroxyamobarbital excreted in feces or urine and/or further oxidation products not yet identified may account for the remainder of the dose.

Chemistry and Stability

Chemistry

Amobarbital sodium is a barbiturate. Amobarbital sodium occurs as a white, friable, granular powder, has a bitter taste, and is hygroscopic. The sodium salt is very soluble in water and soluble in alcohol. After reconstitution with sterile water for injection to a 5% concentration, the commercially available injection has a pH of 9.6-10.4.

Stability

Amobarbital sodium hydrolyzes in solution or when exposed to air, and the injection should be used within 30 minutes after the container is opened. Solutions of amobarbital should not be added to acidic solutions because amobarbital may precipitate at pH 9.2 or less. Solutions for injection should not be used if they contain a precipitate.

Additional Information

For further information on chemistry and stability, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of amobarbital, see the Barbiturates General Statement 28:24.04.

Only references cited for selected revisions after 1984 are available electronically.

750. US Food and Drug Administration. Drug safety communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. Silver Spring, MD; 2016 Dec 14. From FDA website. [Web]

751. Davidson AJ, Disma N, de Graaff JC et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet . 2016; 387:239-50. [PubMed 26507180]

752. Sun LS, Li G, Miller TL et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA . 2016; 315:2312-20. [PubMedCentral][PubMed 27272582]

753. US Food and Drug Administration. Drug safety communication: FDA approves labeling changes for use of general anesthetic and sedation drugs in young children. Silver Spring, MD; 2017 Apr 27. From FDA website. [Web]