Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as sodium:
Amytal Sodium: 500 mg (1 ea)
Pharmacology
Mechanism of Action
An intermediate-acting barbiturate; barbiturates depress the sensory cortex, decrease motor activity, and alter cerebellar function producing drowsiness, sedation, and hypnosis.
Pharmacokinetics/Pharmacodynamics
Metabolism
Primarily hepatic via microsomal enzymes
Excretion
Urine (as metabolites, negligible amounts excreted unchanged in urine); feces (metabolites)
Onset of Action
Rapid, within minutes
Time to Peak
Maximum effect: Hours
Duration of Action
Variable
Half-Life Elimination
16 to 40 hours (mean: 25 hours)
Use: Labeled Indications
Sedative/hypnotic: Use as a sedative, hypnotic, or preanesthetic
Use: Off Label
Therapeutic or diagnostic “Amytal Interviewing” for psychiatric conditionsc
Data from a limited number of clinical trials suggest that amobarbital may be beneficial for therapeutic or diagnostic “Amytal Interviewing” for psychiatric conditions Kavirajan 1999. Additional data may be necessary to further define the role of amobarbital in this setting.
Wada testc
Data from a limited number of clinical trials suggest that amobarbital may be beneficial for determining cerebral dominance to predict the likelihood of a catastrophic memory outcome after surgical resection for the treatment of epilepsy Acharya 1997, Patel 2011. However, more recent evidence suggests the test has less than ideal reliability and validity, and it may pose some risk. Some suggest the intracarotid amobarbital procedure be reserved for patients with atypical or bilateral language representation and when functional MRI is inconclusive Sharan 2011.
Contraindications
Hypersensitivity to barbiturates or any component of the formulation; history of manifest or latent porphyria; marked liver function impairment; marked respiratory disease in which dyspnea or obstruction is evident.
Dosage and Administration
Dosing: Adult
Hypnotic: IM, IV: 65 to 200 mg at bedtime (maximum single dose: 1,000 mg)
Sedative: IM, IV: 30 to 50 mg 2 or 3 times daily (maximum single dose: 1,000 mg)
“Amytal interview” (off-label use): IV: 50 to 100 mg/minute for total dose of 200 to 1,000 mg or until patient experiences drowsiness, impaired attention, slurred speech, or nystagmus (Kavirajan 1999)
Wada test (off-label use): Intra-carotid: 60 to 200 mg (usual dose: 125 mg) over 2 to 5 seconds via percutaneous transfemoral catheter; after 30 to 45 minutes has elapsed since completion of first injection, may repeat dose for evaluation of contralateral hemisphere (Acharya 1997; Patel 2011). Note: Due to the adverse effects associated with intra-carotid amobarbital and questionable reliability and validity, other less invasive tests (eg, functional MRI) may be recommended (Sharan 2011).
Dosing: Geriatric
Avoid use (Beers Criteria [AGS 2019]).
Dosing: Pediatric
Note: Dosage should be individualized with consideration of patient's age, weight, and medical condition. Use of amobarbital as a sedative and as a hypnotic for the treatment of insomnia and as a hypnotic for preoperative sedation has been replaced by newer agents.
Hypnotic (eg, preoperative sedation): Children ≥6 years and Adolescents: IM (preferred), IV: Usual recommendation (Limited data available): 2 to 3 mg/kg/dose; maximum dose: 500 mg/dose; dosing based on generally recognized expert recommendations; published pediatric trial data is lacking (Nelson 1996). The manufacturer describes the ordinary dose range in children 6 to 12 years as 65 to 500 mg and specific dosing recommendations based on patient size are not available; however, in several instances, this may exceed expert weight-based recommendations; if using manufacturer dosing, initiate therapy at the lower end of the range and titrate the dose accordingly.
Intracarotid amobarbital procedure (Wada test): Limited data available; dosing regimens variable: Children ≥6 years and Adolescents: Intra-arterial: 75 to 125 mg/dose; typically administered through femoral arterial catheter; consult institution specific protocols (Acharay 1997; Burns 2009; Hinz 1994; Kim 2007; Szabo 1993)
Reconstitution
Reconstitute with 50 mL SWFI to make a 1% solution; 20 mL SWFI to make a 2.5% solution; 10 mL SWFI to make a 5% solution; 5 mL of SWFI to make a 10% solution; 2.5 mL SWFI to make a 20% solution. The 10% solution is ordinarily used; the 20% solution may be used so that a small volume contains a large dose. Rotate vial to dissolve, do not shake. Do not use unless a clear solution forms within 5 minutes; a solution that forms a precipitate after clearing should not be used. Not more than 30 minutes should elapse from the time the vial is opened until its contents are injected.
Administration
IM: Administer deeply into a large muscle. Do not use more than 5 mL (irrespective of concentration) at any single site (may cause tissue damage). Use 20% solution to facilitate larger doses. Superficial IM or subcutaneous injections may be painful and produce sterile abscesses or sloughs.
IV: Use only when IM administration is not feasible. Administer by slow IV injection (maximum rate of infusion: 50 mg/minute in adults). May administer up to 100 mg/minute when performing “Amytal interview” (off-label use; Kavirajan 1999).
Intra-carotid (off-label route): Wada test (off-label use): Administer dose over 2 to 5 seconds via percutaneous transfemoral catheter into the internal carotid artery (Acharya 1997).
Storage
Store intact vials at 15°C to 30°C (59°F to 86°F). Following reconstitution, solution should be used within 30 minutes.
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Blood Pressure Lowering Agents: Barbiturates may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification
Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Exceptions: Clevidipine. Monitor therapy
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Chloramphenicol (Systemic): May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic). Consider therapy modification
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
CycloSPORINE (Systemic): Barbiturates may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Consider therapy modification
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Estrogen Derivatives (Contraceptive): Barbiturates may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Consider therapy modification
Felbamate: May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Felbamate. Management: Monitor for elevated barbiturate concentrations/toxicity if felbamate is initiated/dose increased, or reduced concentrations/effects if felbamate is discontinued/dose decreased. Refer to phenobarbital dosing guidelines for patients receiving that agent. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Griseofulvin: Barbiturates may decrease the serum concentration of Griseofulvin. Monitor therapy
Hemin: Barbiturates may diminish the therapeutic effect of Hemin. Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of Barbiturates. Management: Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. Consider therapy modification
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
LamoTRIgine: Barbiturates may decrease the serum concentration of LamoTRIgine. Management: See lamotrigine prescribing information for specific age-dependent dosing guidelines regarding concurrent use with a barbiturate, as well as for adjusting lamotrigine dosing if concurrent barbiturate therapy is discontinued. Consider therapy modification
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Methoxyflurane: Barbiturates may enhance the nephrotoxic effect of Methoxyflurane. Barbiturates may increase the metabolism of Methoxyflurane. Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May enhance the CNS depressant effect of Barbiturates. Mianserin may diminish the therapeutic effect of Barbiturates. Barbiturates may decrease the serum concentration of Mianserin. Avoid combination
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Barbiturates. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Primidone: May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Monitor therapy
Progestins (Contraceptive): Barbiturates may diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Propacetamol: Barbiturates may increase the metabolism of Propacetamol. This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. Monitor therapy
Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Barbiturates. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Somatostatin Acetate: May enhance the adverse/toxic effect of Barbiturates. Specifically, Somatostatin Acetate may enhance or prolong Barbiturate effects, including sedative effects. Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Teniposide: Barbiturates may decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Theophylline Derivatives: Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Consider therapy modification
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ulipristal: Barbiturates may decrease the serum concentration of Ulipristal. Avoid combination
Valproate Products: May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Valproate Products. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. An anticoagulant dose increase may be needed after a barbiturate is initiated or given at an increased dose. Anticoagulant dose decreases may be needed following barbiturate discontinuation or dose reduction. Consider therapy modification
Voriconazole: Barbiturates may decrease the serum concentration of Voriconazole. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Adverse Reactions
Frequency not defined and is reported as barbiturate use (not specifically amobarbital).
Cardiovascular: Bradycardia, hypotension, syncope
Central nervous system: Abnormality in thinking, agitation, anxiety, ataxia, central nervous system depression, confusion, dizziness, drowsiness, hallucination, headache, insomnia, nervousness, nightmares, psychiatric disturbance
Gastrointestinal: Constipation, nausea, vomiting
Hematologic & oncologic: Megaloblastic anemia (following chronic phenobarbital use)
Hepatic: Hepatic injury
Hypersensitivity: Hypersensitivity reaction (including angioedema, skin rash, and exfoliative dermatitis)
Local: Injection site reaction
Neuromuscular & skeletal: Hyperkinesia
Respiratory: Apnea, atelectasis (postoperative), hypoventilation
Miscellaneous: Fever
Warnings/Precautions
Concerns related to adverse effects:
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- Paradoxical responses: May cause paradoxical excitement, particularly in patients with acute or chronic pain.
Disease-related concerns:
- Depression: Use with caution, if at all, in patients with depression or suicidal tendencies.
- Drug abuse: Use with caution, if at all, in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
- Hepatic impairment: Use with caution in patients with hepatic impairment, decreased dosage may be needed; contraindicated in severe impairment. Do not administer to patients showing premonitory signs of hepatic coma.
- Hypoadrenalism: Use with caution in patients with borderline hypoadrenal function; even if it is of pituitary or of primary adrenal origin. Systemic effects of exogenous and endogenous corticosteroids may be diminished by amobarbital.
- Renal impairment: Use with caution in patients with renal impairment; decreased dosage may be needed.
- Respiratory disease: Use with caution in patients with respiratory disease; may cause respiratory depression.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Debilitated patient: Use with caution in debilitated patients; may react to barbiturates with marked excitement, depression, and confusion; reduced dosages are recommended.
- Pediatric: Barbiturates repeatedly produce excitement rather than depression in some patients, particularly children.
Dosage form specific issues:
- Alkaline solution: Solution for injection is highly alkaline and extravasation may cause local tissue damage with subsequent necrosis.
Other warnings/precautions:
- Appropriate use: When used as a hypnotic for the treatment of insomnia, effectiveness is limited to ≤2 weeks.
- Administration: Rapid IV administration may cause respiratory depression, apnea, laryngospasm, or vasodilation with a fall in blood pressure; avoid perivascular extravasation or intra-arterial injection; discontinue if patient complains of pain in the limb. Restrict use of IV administration to conditions in which other routes are not feasible, if patient is unconscious (eg, cerebral hemorrhage, eclampsia, or status epilepticus) or patient resists (eg, delirium), or because prompt action is imperative.
- Withdrawal: Abrupt cessation may precipitate withdrawal, including delirium and convulsions (some fatal); withdraw gradually.
Monitoring Parameters
Vital signs and cardiac function during IV administration) renal, and hepatic function with prolonged therapy.
Pregnancy
Pregnancy Risk Factor
D
Pregnancy Considerations
Barbiturates cross the placenta and distribute in fetal tissue. Teratogenic effects have been reported with first trimester exposure. Exposure during the third trimester may lead to symptoms of acute withdrawal following delivery; symptoms may be delayed up to 14 days.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue. Have patient report immediately to prescriber signs of depression (thoughts of suicide, anxiety, emotional instability, or confusion), difficulty breathing, slow breathing, shallow breathing, or severe injection site pain, burning, redness, or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
