Secobarbital

Pronunciation

(see koe BAR bi tal)

U.S. Brand Names

Seconal®

Synonyms

Quinalbarbitone Sodium; Secobarbital Sodium

Generic Available

No

Use

Preanesthetic agent; short-term treatment of insomnia

Restrictions

C-II

Pregnancy Risk Factor

D

Lactation

Enters breast milk/use caution (AAP rates "compatible")

Contraindications

Hypersensitivity to barbiturates or any component of the formulation; marked hepatic impairment; dyspnea or airway obstruction; porphyria; pregnancy

Warnings/Precautions

Should be used only after evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7-10 days may indicate psychiatric or medical illness. Potential for drug dependency exists, abrupt cessation may precipitate withdrawal, including status epilepticus in epileptic patients. Do not administer to patients in acute pain. Use caution in elderly, debilitated, renally impaired, or pediatric patients. May cause paradoxical responses, including agitation and hyperactivity, particularly in acute pain and pediatric patients. Use with caution in patients with depression or suicidal tendencies, or in patients with a history of drug abuse. Tolerance, psychological and physical dependence may occur with prolonged use. Use with caution in patients with hepatic function impairment. May cause CNS depression, which may impair physical or mental abilities. Patients must cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated. May cause respiratory depression or hypotension, Use with caution in hemodynamically unstable patients or patients with respiratory disease.

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypotension

Central nervous system: Dizziness, lightheadedness, "hangover" effect, drowsiness, CNS depression, fever, confusion, mental depression, unusual excitement, nervousness, faint feeling, headache, insomnia, nightmares, hallucinations

Dermatologic: Exfoliative dermatitis, rash, Stevens-Johnson syndrome

Gastrointestinal: Nausea, vomiting, constipation

Hematologic: Agranulocytosis, megaloblastic anemia, thrombocytopenia, thrombophlebitis, urticaria apnea

Local: Pain at injection site

Respiratory: Respiratory depression, laryngospasm

Overdosage/Toxicology

Symptoms of overdose include unsteady gait, slurred speech, confusion, jaundice, hypothermia, fever, hypotension, respiratory depression, and coma. Charcoal hemoperfusion or hemodialysis may be useful, especially in the presence of very high serum barbiturate levels when the patient is in shock, coma, or renal failure. Forced alkaline diuresis is of no value in the treatment of intoxications with short-acting barbiturates.

Drug Interactions

Induces CYP2A6 (strong), 2C8/9 (strong)

Acetaminophen: Barbiturates may enhance the hepatotoxic potential of acetaminophen overdoses

Antiarrhythmics: Barbiturates may increase the metabolism of antiarrhythmics, decreasing their clinical effect; includes disopyramide, propafenone, and quinidine

Anticonvulsants: Barbiturates may increase the metabolism of anticonvulsants; includes ethosuximide, felbamate (possibly), lamotrigine, phenytoin, tiagabine, topiramate, and zonisamide; does not appear to affect gabapentin or levetiracetam

Antineoplastics: Limited evidence suggests that enzyme-inducing anticonvulsant therapy may reduce the effectiveness of some chemotherapy regimens (specifically in ALL); teniposide and methotrexate may be cleared more rapidly in these patients

Antipsychotics: Barbiturates may enhance the metabolism (decrease the efficacy) of antipsychotics; monitor for altered response; dose adjustment may be needed

Beta-blockers: Metabolism of beta-blockers may be increased and clinical effect decreased; atenolol and nadolol are unlikely to interact given their renal elimination

Calcium channel blockers: Barbiturates may enhance the metabolism of calcium channel blockers, decreasing their clinical effect

Chloramphenicol: Barbiturates may increase the metabolism of chloramphenicol and chloramphenicol may inhibit barbiturate metabolism; monitor for altered response

Cimetidine: Barbiturates may enhance the metabolism of cimetidine, decreasing its clinical effect

CNS depressants: Sedative effects and/or respiratory depression with barbiturates may be additive with other CNS depressants; monitor for increased effect; includes ethanol, sedatives, antidepressants, narcotic analgesics, and benzodiazepines

Corticosteroids: Barbiturates may enhance the metabolism of corticosteroids, decreasing their clinical effect

Cyclosporine: Levels may be decreased by barbiturates; monitor

CYP2A6 substrates: Secobarbital may decrease the levels/effects of CYP2A6 substrates. Example substrates include ifosfamide and rifampin.

CYP2C8/9 substrates: Secobarbital may decrease the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, losartan, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, sulfonamides, warfarin, and zafirlukast.

Doxycycline: Barbiturates may enhance the metabolism of doxycycline, decreasing its clinical effect; higher dosages may be required

Estrogens: Barbiturates may increase the metabolism of estrogens and reduce their efficacy

Felbamate may inhibit the metabolism of barbiturates and barbiturates may increase the metabolism of felbamate

Griseofulvin: Barbiturates may impair the absorption of griseofulvin, and griseofulvin metabolism may be increased by barbiturates, decreasing clinical effect

Guanfacine: Effect may be decreased by barbiturates

Immunosuppressants: Barbiturates may enhance the metabolism of immunosuppressants, decreasing its clinical effect; includes both cyclosporine and tacrolimus

Loop diuretics: Metabolism may be increased and clinical effects decreased; established for furosemide, effect with other loop diuretics not established

MAO inhibitors: Metabolism of barbiturates may be inhibited, increasing clinical effect or toxicity of the barbiturates

Methadone: Barbiturates may enhance the metabolism of methadone resulting in methadone withdrawal

Methoxyflurane: Barbiturates may enhance the nephrotoxic effects of methoxyflurane

Oral contraceptives: Barbiturates may enhance the metabolism of oral contraceptives, decreasing their clinical effect; an alternative method of contraception should be considered

Theophylline: Barbiturates may increase metabolism of theophylline derivatives and decrease their clinical effect

Tricyclic antidepressants: Barbiturates may increase metabolism of tricyclic antidepressants and decrease their clinical effect; sedative effects may be additive

Valproic acid: Metabolism of barbiturates may be inhibited by valproic acid; monitor for excessive sedation; a dose reduction may be needed

Warfarin: Barbiturates inhibit the hypoprothrombinemic effects of oral anticoagulants via increased metabolism; this combination should generally be avoided

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Compatibility

I.V. form is incompatible when mixed with benzquinamide (in syringe), cimetidine (same syringe), codeine, erythromycin, glycopyrrolate (same syringe), hydrocortisone, insulin, levorphanol, methadone, norepinephrine, pentazocine, phenytoin, sodium bicarbonate, tetracycline, and vancomycin.

Mechanism of Action

Depresses CNS activity by binding to barbiturate site at GABA-receptor complex enhancing GABA activity, depressing reticular activity system; higher doses may be gabamimetic

Pharmacodynamics/Kinetics

Onset of hypnosis: 15-30 minutes

Duration: 3-4 hours with 100 mg dose

Distribution: 1.5 L/kg; crosses the placenta; appears in breast milk

Protein binding: 45% to 60%

Metabolism: Hepatic, by microsomal enzyme system

Half-life elimination: 15-40 hours, mean: 28 hours

Time to peak, serum: Within 2-4 hours

Excretion: Urine (as inactive metabolites, small amounts as unchanged drug)

Dosage

Oral:

Children:

Preoperative sedation: 2-6 mg/kg (maximum dose: 100 mg/dose) 1-2 hours before procedure

Sedation: 6 mg/kg/day divided every 8 hours

Adults:

Hypnotic: Usual: 100 mg/dose at bedtime; range 100-200 mg/dose

Preoperative sedation: 100-300 mg 1-2 hours before procedure

Monitoring Parameters

Blood pressure, heart rate, respiratory rate, CNS status

Patient Education

Use exactly as directed; do not increase dose or frequency or discontinue without consulting prescriber. Drug may cause physical and/or psychological dependence. While using this medication, do not use alcohol or other prescription or OTC medications (especially, pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or constipation (increased exercise, fluids, fruit, or fiber may help). Report skin rash or irritation; CNS changes (confusion, depression, increased sedation, excitation, headache, insomnia, or nightmares); respiratory difficulty or shortness of breath; difficulty swallowing or feeling of tightness in throat; unusual weakness or unusual bleeding in mouth, urine, or stool; or other unanticipated adverse effects. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication. Use appropriate barrier contraceptive measures. Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Dosage Forms

Capsule, as sodium: 100 mg

References

Levine HL, Cohen ME, Duffner PK, et al, "Rectal Absorption and Disposition of Secobarbital in Epileptic Children,"Pediatr Pharmacol (New York), 1982, 2(1):33-8.

Monteil RA, Raybaud H, Madinier I, et al, "Occurrence of Oral Mucosal Necrosis in a Patient With Barbiturate-Induced Coma,"Oral Surg Oral Med Oral Pathol, 1991, 72(5):562-4.

Nahata MC, Starling S, and Edwards RC, "Prolonged Sedation Associated With Secobarbital in Newborn Infants Receiving Ventilatory Support,"Am J Perinatol, 1991, 8(1):35-6.

Tracqui A, Kintz P, Mangin P, et al, "A Fatality Involving Secobarbital, Nitrazepam, and Codeine,"Am J Forensic Med Pathol, 1989, 10(2):130-3.

Wolfert RR and Cox RM, "Room Temperature Stability of Drug Products Labeled for Refrigerated Storage,"Am J Hosp Pharm, 1975, 32(6):585-7.

International Brand Names

Seconal Sodium® (GB)

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