Version July 2025
Note: Adjust dose based on patient's age, weight, and condition.
Sedative/preanesthesia:
IM: 150 to 200 mg, as a single dose.
IV: Initial: 100 mg; if needed, may administer additional increments after at least 1 minute, up to a total dose of 200 to 500 mg.
Seizures: IV: Note: Mechanical ventilation and cardiovascular monitoring required; titrate dose to cessation of electrographic seizures or burst suppression (Ref).
Neurocritical Care Society recommendations (Ref):
Loading dose: 5 to 15 mg/kg administered at a rate of ≤50 mg/minute, may give additional 5 to 10 mg/kg; follow with a continuous infusion.
Continuous infusion: 0.5 to 5 mg/kg/hour. If the patient experiences breakthrough status epilepticus while on continuous infusion, administer an additional 5 mg/kg bolus and increase infusion rate by 0.5 to 1 mg/kg/hour every 12 hours. Note: A period of at least 24 to 48 hours of electrographic control is recommended prior to withdrawing the continuous infusion; withdraw gradually to prevent recurrent status epilepticus.
Barbiturate coma in severe brain injury patients/elevated intracranial pressure (off-label use): IV: Loading dose: 10 mg/kg given over 30 minutes (or ≤25 mg/minute), followed by 5 mg/kg every hour for 3 doses; monitor blood pressure and respiratory rate. Maintenance infusion: Initial: 1 mg/kg/hour; may increase to 2 to 4 mg/kg/hour; maintain burst suppression on EEG (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling. However, a reduced dosage is recommended.
Note: A risk of propylene glycol toxicity exists in patients receiving pentobarbital, especially in patients with renal impairment; monitor closely (eg, osmolal gap) if using for prolonged periods of time or at high doses (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling. However, a reduced dosage is recommended.
Avoid use (Ref).
(For additional information see "Pentobarbital: Pediatric drug information")
Note: Adjust dose based on patient's age, weight, kidney and liver function, and medical condition. Consider the potential for delayed metabolism or elimination in infants <6 months of age (Ref).
Hypnotic: Note: Use has generally been replaced by other agents.
Infants, Children, and Adolescents: IM: 2 to 6 mg/kg/dose; maximum dose: 100 mg/dose.
Procedural sedation: Note: Use has generally been replaced by other agents.
IM: Infants, Children, and Adolescents: IM: 2 to 6 mg/kg; maximum dose: 100 mg/dose (Ref).
IV: Infants, Children, and Adolescents: IV: Initial: 1 to 2 mg/kg/dose; additional doses of 1 to 2 mg/kg every 3 to 5 minutes to desired effect; usual effective total dose: 1 to 6 mg/kg; maximum total dose: 100 mg (Ref). Note: Patients receiving concurrent barbiturate therapy may require higher total mg/kg doses (up to 9 mg/kg) (Ref).
Oral: Limited data available:
Infants: Oral: Initial: 4 mg/kg/dose; if needed, may administer supplemental doses of 2 to 4 mg/kg/dose every 30 minutes; maximum total dose: 8 mg/kg (Ref).
Children <4 years: Oral: 3 to 6 mg/kg/dose; maximum dose: 100 mg/dose (Ref).
Children ≥4 years and Adolescents: Oral: 1.5 to 3 mg/kg/dose; maximum dose: 100 mg/dose (Ref).
Rectal: Limited data available:
Children <4 years: Rectal: 3 to 6 mg/kg/dose; maximum dose: 100 mg/dose (Ref).
Children ≥4 years and Adolescents: Rectal: 1.5 to 3 mg/kg/dose; maximum dose: 100 mg/dose (Ref).
Reduction of elevated intracranial pressure (ICP): Limited data available: Note: Intubation is required; adjust dose based on hemodynamics, ICP, cerebral perfusion pressure, and EEG; continuous arterial blood pressure monitoring and cardiovascular support are recommended (Ref).
Children and Adolescents: Note: Reserve higher doses for use in patients with refractory intracranial hypertension (Ref).
Bolus dose: IV: 5 to 10 mg/kg over 20 to 30 minutes; may repeat 5 mg/kg as needed based on clinical response and clinical target (Ref).
Continuous IV infusion: Initial: 1 mg/kg/hour; adjust to maintain burst suppression on EEG; maintenance dose range: 1 to 2 mg/kg/hour (Ref).
Sedation of mechanically ventilated ICU patient (alternative agent): Limited data available:
Infants, Children, and Adolescents: IV: Loading dose: 1 mg/kg followed by a continuous IV infusion of 1 mg/kg/hour. Additional boluses at a dose equal to hourly rate may be given every 2 hours as needed. If ≥4 to 6 boluses are administered within 24 hours, then increase maintenance rate by 1 mg/kg/hour; reported required range: 1 to 6 mg/kg/hour (median: 2 mg/kg/hour). Tapering of dose and/or conversion to oral phenobarbital has been reported for therapy ≥5 days (Ref). Note: Higher rates of adverse effects were observed in a small report that used higher loading and initial maintenance doses (Ref).
Status epilepticus refractory to standard therapy: Note: Mechanical ventilation and cardiovascular monitoring required; monitor blood pressure and respiratory rate; titrate dose to cessation of electrographic seizures or burst suppression (Ref).
Infants, Children, and Adolescents:
Loading dose: IV: Usual dose: 5 mg/kg; doses up to 15 mg/kg have been described; administration >50 mg/minute is not recommended (Ref).
Continuous IV infusion: Initial: 0.5 to 1 mg/kg/hour; may increase up to 5 mg/kg/hour; maintain burst suppression on EEG for 24 to 48 hours (no seizure activity); if the patient experiences breakthrough status epilepticus while on continuous infusion, administer an additional 5 mg/kg bolus and increase infusion rate by 0.5 to 1 mg/kg/hour every 12 hours until burst suppression (Ref). Note: Withdraw gradually to prevent withdrawal seizures (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, a reduced dosage is recommended.
Note: A risk of propylene glycol toxicity exists in patients receiving pentobarbital, especially in patients with renal impairment; monitor closely (eg, osmolar gap) if using for prolonged periods of time or at high doses (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, a reduced dosage is recommended.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Bradycardia, hypotension, syncope
Central nervous system: Abnormality in thinking, agitation, anxiety, ataxia, central nervous system stimulation, confusion, depression, dizziness, drowsiness, hallucination, headache, insomnia, nervousness, nightmares, psychiatric disturbance
Dermatologic: Exfoliative dermatitis, skin rash
Gastrointestinal: Constipation, nausea, vomiting
Hematologic & oncologic: Megaloblastic anemia
Hepatic: Hepatotoxicity
Hypersensitivity: Angioedema, hypersensitivity reaction
Local: Injection site reaction
Neuromuscular & skeletal: Hyperkinesia, laryngospasm
Respiratory: Apnea (especially with rapid IV use), hypoventilation, respiratory depression
Miscellaneous: Fever
Hypersensitivity to barbiturates or any component of the formulation; porphyria.
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).
• Respiratory depression: May cause respiratory depression particularly when administered intravenously; use with caution in patients with respiratory disease. Intubation is typically required prior to treatment for seizures or traumatic brain injury (NCS [Brophy 2012]).
Disease-related concerns:
• Depression: Use with caution in patients with depression or suicidal tendencies.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduce dose as appropriate. Do not use in patients showing premonitory signs of hepatic coma.
• Renal impairment: Use with caution in patients with renal impairment; reduce dose as appropriate.
• Substance abuse: Use with caution in patients with a history of drug abuse; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
Special populations:
• Debilitated patients: Use with caution in patients who are debilitated; marked excitement, depression, and confusion may occur.
• Older adult: Use with caution in older adult patients; marked excitement, depression, and confusion may occur.
• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems, including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling.
Other warnings/precautions:
• Acute or chronic pain: Use caution when administering to patients with acute or chronic pain; paradoxical excitement could be induced or important symptoms could be masked.
• Appropriate use: IV administration: Too rapid IV administration may cause respiratory depression, apnea, laryngospasm, or vasodilation with hypotension.
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on the child's or fetus' brain development and may contribute to various cognitive and behavioral problems; the FDA is requiring warnings be included in the manufacturer's labeling for all general anesthetic/sedative drugs. Multiple animal species studies have shown adverse effects on brain maturation; in juvenile animals, drugs that potentiate GABA activity and/or block NMDA receptors for >3 hours demonstrated widespread neuronal and oligodendrocyte cell loss along with alteration in synaptic morphology and neurogenesis. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and attention deficit hyperactivity disorder (ADHD). Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. Further studies are needed to fully characterize findings and ensure that these findings are not related to underlying conditions or the procedure itself. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection, as sodium:
Nembutal: 50 mg/mL (20 mL [DSC], 50 mL [DSC]) [latex free; contains alcohol, usp, propylene glycol]
Generic: 50 mg/mL (20 mL, 50 mL)
Solution, Injection, as sodium [preservative free]:
Generic: 50 mg/mL (20 mL, 50 mL)
Yes
Solution (PENTObarbital Sodium Injection)
50 mg/mL (per mL): $72.60 - $72.62
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C-II
Administer by deep IM or slow IV injection.
IM: Inject into a large muscle. No more than 5 mL (250 mg) should be injected at any one site because of possible tissue irritation.
IV: Do not exceed 50 mg/minute; IV push doses may be given undiluted. Parenteral solutions are highly alkaline; may be an irritant; avoid extravasation. Avoid intra-arterial injection. Discontinue administration of injection if patient complains of limb pain.
Parenteral:
IM: May be administered by deep IM; inject into a large muscle. No more than 5 mL should be injected at any one site because of possible tissue irritation.
IV:
Intermittent IV injection: Administer undiluted (50 mg/mL) by slow IV injection; infuse over 10 to 30 minutes not to exceed 50 mg/minute; rapid IV injection may cause respiratory depression, apnea, laryngospasm, bronchospasm, and hypotension; loading doses have been infused over 30 to 160 minutes in traumatic brain injury patients to decrease the risk of hypotension and decrease cerebral perfusion pressure (Ref).
Continuous IV infusion: Administer at a concentration ≤50 mg/mL via infusion pump; if administering diluted solution monitor for precipitation (Ref). Solution highly alkaline (pH=9.5); care should be taken to avoid extravasation; consider administration using large bore vein (not hand or wrist) or via a running IV line at port farthest from patient's vein.
Oral: Parenteral solution may be mixed with flavored (eg, cherry) syrup prior to administration to improve palatability (Ref).
Sedative/preanesthesia: Short-term (<2 weeks) treatment of insomnia or as preanesthesia.
Limitations of use: Note: The manufacturer labeling includes indications as a hypnotic for short-term treatment of insomnia; however, pentobarbital is no longer recommended to be used this way (Schutte-Rodin 2008).
Seizures: Emergency control of certain anticonvulsive episodes (eg, status epilepticus, cholera, eclampsia, meningitis, tetanus, toxic reactions to strychnine or local anesthetics).
Barbiturate coma in severe brain injury patients/elevated intracranial pressure
PENTobarbital may be confused with PHENobarbital
Nembutal may be confused with Myambutol
Beers Criteria: Pentobarbital is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its high rate of physical dependence, tolerance to sleep benefits, and increased risk of overdose at low dosages (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Blood Pressure Lowering Agents: Barbiturates may increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Disulfiram: May increase adverse/toxic effects of Products Containing Propylene Glycol. A disulfiram reaction may occur. Management: Consider avoiding concomitant use of disulfiram and products that contain propylene glycol. Note that not all preparations or dosage forms of a specific drug will contain propylene glycol. Risk D: Consider Therapy Modification
Doxycycline: Barbiturates may decrease serum concentration of Doxycycline. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Griseofulvin: Barbiturates may decrease serum concentration of Griseofulvin. Risk C: Monitor
Hemin: Barbiturates may decrease therapeutic effects of Hemin. Risk X: Avoid
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: Barbiturates may increase nephrotoxic effects of Methoxyflurane. Barbiturates may increase metabolism of Methoxyflurane. Risk X: Avoid
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoprolol: PENTobarbital may increase hypotensive effects of Metoprolol. PENTobarbital may decrease serum concentration of Metoprolol. Risk C: Monitor
MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid
MetroNIDAZOLE (Topical): May increase adverse/toxic effects of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May increase CNS depressant effects of Barbiturates. Mianserin may decrease therapeutic effects of Barbiturates. Barbiturates may decrease serum concentration of Mianserin. Risk X: Avoid
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease serum concentration of Barbiturates. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: Barbiturates may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid
OxyCODONE: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Secnidazole: Products Containing Propylene Glycol may increase adverse/toxic effects of Secnidazole. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Theophylline Derivatives: Barbiturates may decrease serum concentration of Theophylline Derivatives. Risk C: Monitor
Tricyclic Antidepressants: Barbiturates may increase metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Risk D: Consider Therapy Modification
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valproic Acid and Derivatives: May increase CNS depressant effects of Barbiturates. Valproic Acid and Derivatives may increase serum concentration of Barbiturates. Barbiturates may decrease serum concentration of Valproic Acid and Derivatives. Risk C: Monitor
Vitamin K Antagonists: Barbiturates may increase metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. Anticoagulant dose increases of 30% to 60% 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. Risk D: Consider Therapy Modification
Zolpidem: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Barbiturates can be detected in the placenta, fetal liver and fetal brain.
Outcome data following maternal use of pentobarbital during pregnancy are available (Heinonen 1977). Fetal and maternal blood concentrations may be similar following parenteral barbiturate administration. An increased incidence of fetal abnormalities may occur following maternal barbiturate use. When used during the third trimester of pregnancy, withdrawal symptoms may occur in the neonate including seizures and hyperirritability; symptoms may be delayed up to 14 days. Respiratory depression may occur in the newborn when sedative-hypnotic barbiturates are administered to the mother during labor; resuscitation equipment should be available, especially for premature infants. Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D- aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity, may affect brain development. Human fetuses may be most vulnerable during the third trimester.
Treatment of status epilepticus during pregnancy should consider gestational age and etiology of seizures (eg, eclampsia versus other causes) (NCS [Brophy 2012], Rajiv 2019).
Use of pentobarbital for refractory intracranial hypertension in a pregnant patient has been described in a case report (Patel 2022).
Use of hypnotic doses during labor does not impair uterine activity; however, use of full anesthetic doses decreases the force and frequency of uterine contractions. The American College of Obstetricians and Gynecologists (ACOG) recommends that pregnant patients should not be denied medically indicated surgery or procedures, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 2019).
Pentobarbital is present in breast milk (Wilson 1980).
The manufacturer recommends that caution be exercised when administering pentobarbital to patients who are breastfeeding.
Respiratory status (for conscious sedation, includes pulse oximetry), cardiovascular status, CNS status; cardiac monitor and blood pressure monitor required; clinical signs of propylene glycol toxicity (for continuous high-dose and/or long duration IV use), including serum creatinine, BUN, serum lactate, and osmolal gap (Miller 2008; Pillai 2014). Monitor infusion site.
Barbiturate coma: Monitor oxygenation as well as arterial and central venous pressures to guide fluid and vasoactive therapy for maintenance of blood pressure; temperature
Elevated ICP: Monitor ICP, CPP, EEG
Therapeutic:
Sedation: 1 to 5 mcg/mL (SI: 4.4 to 22.1 micromole/L).
Coma or intracranial pressure therapy: Target: 30 to 40 mcg/mL (SI: 132.6 to 176.8 micromole/L) (Eisenberg 1988).
Potentially toxic: >10 mcg/mL (SI: >44.2 micromole/L); dependent on reason for use and patient condition.
Barbiturate with sedative, hypnotic, and antiseizure properties. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. In high doses, barbiturates exhibit antiseizure activity; barbiturates produce dose-dependent respiratory depression; reduce brain metabolism and cerebral blood flow in order to decrease intracranial pressure
Onset of action (Krauss 2006): Children and Adults: Sedation: IM: 10 to 15 minutes; IV: Almost immediate, within 3 to 5 minutes; Oral, Rectal: 15 to 60 minutes
Duration (Krauss 2006): Children and Adults: Sedation: IM: 1 to 2 hours; IV: 15 to 45 minutes; Oral, Rectal: 1 to 4 hours
Distribution: Vd: Children: 0.8 L/kg (Schaible 1982); Adults: 1 L/kg (Ehrnebo 1974)
Protein binding: 45% to 70%
Metabolism: Hepatic via hydroxylation and glucuronidation (Wermeling 1985)
Half-life elimination: Terminal: Children: 26 ± 16 hours (Schaible 1982); Adults: Healthy: 22 hours (average) (Ehrnebo 1974); Range: 15 to 50 hours; dose dependent
Excretion: Urine (<1%, as unchanged drug)
