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PENTobarbital

Pronunciation

(pen toe BAR bi tal)

Index Terms

  • Pentobarbital Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as sodium:

Nembutal: 50 mg/mL (20 mL, 50 mL) [latex free; contains alcohol, usp, propylene glycol]

Brand Names: U.S.

  • Nembutal

Pharmacologic Category

  • Anticonvulsant, Barbiturate
  • Barbiturate

Pharmacology

Barbiturate with sedative, hypnotic, and anticonvulsant properties. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. In high doses, barbiturates exhibit anticonvulsant activity; barbiturates produce dose-dependent respiratory depression; reduce brain metabolism and cerebral blood flow in order to decrease intracranial pressure

Distribution

Vd: Children: 0.8 L/kg (Schaible 1982); Adults: 1 L/kg (Ehrnebo 1974)

Metabolism

Hepatic via hydroxylation and glucuronidation (Wermeling, 1985)

Excretion

Urine (<1%, as unchanged drug)

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 of Action

Krauss 2006: Children and Adults: Sedation: IM: 1 to 2 hours; IV: 15 to 45 minutes; Oral, Rectal: 1 to 4 hours

Half-Life Elimination

Terminal: Children: 26 ± 16 hours (Schaible 1982); Adults: Healthy: 22 hours (average) (Ehrnebo 1974); Range: 15 to 50 hours; dose dependent

Protein Binding

45% to 70%

Use: Labeled Indications

Sedative/hypnotic; status epilepticus (refractory)

Use: Unlabeled

Barbiturate coma in patients with severe brain injury (eg, hemorrhagic stroke, traumatic brain injury) and increased intracranial pressure

Contraindications

Hypersensitivity to barbiturates or any component of the formulation; porphyria

Dosing: Adult

Note: Adjust dose based on patient's age, weight, and condition.

Hypnotic/sedative:

IM: 150 to 200 mg

IV: Initial: 100 mg; decrease dose for elderly or debilitated patients. If needed, may administer additional increments after at least 1 minute, up to a total dose of 200 to 500 mg

Barbiturate coma in severe brain injury patients/elevated intracranial pressure (off-label use; Bratton, 2007): 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.

Status epilepticus, refractory: IV: Note: Mechanical ventilation and cardiovascular monitoring required; titrate dose to cessation of electrographic seizures or burst suppression (NCS [Brophy, 2012]).

Neurocritical Care Society recommendations (NCS [Brophy, 2012]):

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

Dosing: Geriatric

Not recommended for use in the elderly; decrease dose if use becomes necessary.

Dosing: Pediatric

Note: Adjust dose based on patient's age, weight, and condition.

Hypnotic/sedative:

IM: 2 to 6 mg/kg; maximum: 100 mg/dose

IV: 1 to 6 mg/kg titrated in 1 to 2 mg/kg increments every 3 to 5 minutes to desired effect (Krauss, 2006)

Status epilepticus, refractory: IV: Note: Mechanical ventilation and cardiovascular monitoring required; titrate dose to cessation of electrographic seizures or burst suppression (NCS [Brophy, 2012]).

Neurocritical Care Society recommendations:

Loading dose: 5 to 15 mg/kg administered slowly (eg, over 60 to 120 minutes [maximum rate: 50 mg/minute]), may give additional 5 to 10 mg/kg; follow with a continuous infusion (NCS [Brophy, 2012]; Phelps, 2013).

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 (NCS [Brophy, 2012])

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling. However, a reduced dosage in patients with renal dysfunction is recommended.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. However, a reduced dosage in patients with liver dysfunction is recommended.

Administration

Pentobarbital may be administered 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:

Adults: Do not exceed 50 mg/minute; IV push doses may be given undiluted. Parenteral solutions are highly alkaline; avoid extravasation; avoid intra-arterial injection.

Pediatric patients: Status epilepticus: Administer loading doses over 60 to 120 minutes (maximum rate: 50 mg/minute). Administer bolus doses over 10 to 30 minutes (Phelps, 2013).

Compatibility

Stable in D5LR, D51/4NS, D51/2NS, D5NS, D10W, LR, 1/2NS.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, fenoldopam.

Compatibility in syringe: Incompatible with butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydroxyzine, meperidine, midazolam, nalbuphine, pentazocine, prochlorperazine edisylate, promethazine, ranitidine.

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F); brief excursions of 15°C to 30°C (59°F to 86°F) permitted. Protect from freezing and avoid excessive heat. When mixed with an acidic solution, precipitate may form. Use only clear solution.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). 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

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other 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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chloramphenicol: May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Contraceptives (Estrogens): Barbiturates may diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Consider therapy modification

Contraceptives (Progestins): Barbiturates may diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

CycloSPORINE (Systemic): Barbiturates may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification

CYP2A6 Substrates: CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dimethindene: 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 (e.g., opioids, barbiturates) with concomitant use. 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: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. 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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Meperidine: Barbiturates may enhance the CNS depressant effect of Meperidine. Barbiturates may increase serum concentrations of the active metabolite(s) of Meperidine. 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

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: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. 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

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. 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 [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. 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

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: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. 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

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

Thiazide and Thiazide-Like Diuretics: Barbiturates may enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. 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

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.

Cardiovascular: Bradycardia, hypotension, syncope

Central nervous system: Abnormal thinking, agitation, anxiety, ataxia, CNS excitation, confusion, depression, dizziness, drowsiness, fever, hallucinations, headache, hyperkinesia, insomnia, nervousness, nightmares, psychiatric disturbances, somnolence

Dermatologic: Angioedema, exfoliative dermatitis, rash

Gastrointestinal: Constipation, nausea, vomiting

Hematologic: Megaloblastic anemia

Hepatic: Hepatotoxicity

Local: Injection site reactions

Respiratory: Apnea (especially with rapid IV use), hypoventilation, laryngospasm, respiratory depression

Miscellaneous: Gangrene with inadvertent intra-arterial injection, hypersensitivity reactions

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).

• Hypotension: May cause hypotension particularly when administered intravenously; use with caution in hemodynamically unstable patients (hypotension or shock). High doses used to induce pentobarbital coma cause hypotension requiring vasopressor therapy.

• 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 status epilepticus or traumatic brain injury.

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 with 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.

Concurrent drug therapy issues:

• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.

Special populations:

• Debilitated patients: Use with caution in patients who are debilitated.

Dosage form specific issues:

• Alkaline solution: Solution for injection is highly alkaline and extravasation may cause local tissue damage.

• Propylene glycol toxicity: Intravenous solution may contain propylene glycol (PG). One case report has described a patient who developed lactic acidosis possibly secondary to PG accumulation following a continuous infusion of pentobarbital (Miller, 2008). Consider monitoring for signs of PG toxicity (eg, lactic acidosis, acute renal failure, osmol gap) in patients who require a continuous infusion of pentobarbital.

Other warnings/precautions:

• Acute pain: Do not administer to patients in acute pain; may heighten/worsen sense of pain.

• Withdrawal: Anticonvulsants 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.

Monitoring Parameters

Respiratory status (for conscious sedation, includes pulse oximetry), cardiovascular status, CNS status; cardiac monitor and blood pressure monitor required

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

Pregnancy Risk Factor

D

Pregnancy Considerations

Barbiturates can be detected in the placenta, fetal liver and fetal brain. Fetal and maternal blood concentrations may be similar following parenteral administration. An increased incidence of fetal abnormalities may occur following maternal 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. Use during labor does not impair uterine activity; however, respiratory depression may occur in the newborn; resuscitation equipment should be available, especially for premature infants.

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 difficulty breathing; slow breathing; shallow breathing; severe dizziness; passing out; anxiety; confusion; depression; severe loss of strength and energy; or severe injection site redness, burning, pain, edema, 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 health care 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.

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