Yes

Anticonvulsant, Barbiturate; Barbiturate

Management of generalized tonic-clonic (grand mal) and partial seizures; sedative

C-IV

D

Clinical effects on the fetus: Crosses the placenta. Cardiac defect reported; hemorrhagic disease of newborn due to fetal vitamin K depletion may occur; may induce maternal folic acid deficiency; withdrawal symptoms observed in infant following delivery. Epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of anticonvulsant therapy. Benefit:risk ratio usually favors continued use during pregnancy and breast-feeding.

Breast-feeding/Lactation: Crosses into breast milk

Clinical effects on the infant: Sedation; withdrawal with abrupt weaning reported. American Academy of Pediatrics recommends USE WITH CAUTION.

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

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 or hepatic dysfunction, and 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. May cause CNS depression, which may impair physical or mental abilities. Patients must be cautioned about performing tasks which require mental alertness (ie, operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated. May cause respiratory depression or hypotension, particularly when administered intravenously. Use with caution in hemodynamically unstable patients (hypovolemic shock, CHF) or patients with respiratory disease. Due to its long half-life and risk of dependence, phenobarbital is not recommended as a sedative in the elderly. Use has been associated with cognitive deficits in children. Use with caution in patients with hypoadrenalism.

Cardiovascular: Bradycardia, hypotension, syncope

Central nervous system: Drowsiness, lethargy, CNS excitation or depression, impaired judgment, "hangover" effect, confusion, somnolence, agitation, hyperkinesia, ataxia, nervousness, headache, insomnia, nightmares, hallucinations, anxiety, dizziness

Dermatologic: Rash, exfoliative dermatitis, Stevens-Johnson syndrome

Gastrointestinal: Nausea, vomiting, constipation

Hematologic: Agranulocytosis, thrombocytopenia, megaloblastic anemia

Local: Pain at injection site, thrombophlebitis with I.V. use

Renal: Oliguria

Respiratory: Laryngospasm, respiratory depression, apnea (especially with rapid I.V. use), hypoventilation, apnea

Miscellaneous: Gangrene with inadvertent intra-arterial injection

Symptoms of overdose include unsteady gait, slurred speech, confusion, jaundice, hypothermia, hypotension, respiratory depression, coma

If hypotension occurs, administer I.V. fluids and place the patient in the Trendelenburg position. If unresponsive, an I.V. vasopressor (eg, dopamine, epinephrine) may be required.

Repeated oral doses of activated charcoal significantly reduce the half-life of phenobarbital resulting from an enhancement of nonrenal elimination. The usual dose is 0.1-1 g/kg every 4-6 hours for 3-4 days unless the patient has no bowel movement causing the charcoal to remain in the GI tract. Assure adequate hydration and renal function. Urinary alkalinization with I.V. sodium bicarbonate also helps to enhance elimination. Hemodialysis or hemoperfusion is of uncertain value. Patients in stage IV coma due to high serum barbiturate levels may require charcoal hemoperfusion.

CYP1A2, 2B6, 2C, 2C8, 3A3/4, and 3A5-7 inducer

Decreased effect: Phenobarbital may reduce the efficacy of beta-blockers, chloramphenicol, cimetidine, clozapine, corticosteroids, cyclosporine, disopyramide, doxycycline, ethosuximide, furosemide, griseofulvin, haloperidol, lamotrigine, methadone, nifedipine, oral contraceptives, phenothiazine, phenytoin, propafenone, psychotropics, quinidine, tacrolimus, TCAs, theophylline, warfarin, and verapamil

Increased toxicity when combined with other CNS depressants, benzodiazepines, valproic acid, chloramphenicol, or antidepressants; respiratory and CNS depression may be additive

MAOIs may prolong the effect of phenobarbital

Barbiturates stimulate the metabolism of beta-blockers and decrease their serum concentrations; consider a renally-eliminated beta-blocker (atenolol, nadolol)

Barbiturates may enhance the hepatotoxic potential of acetaminophen via an increased formation of toxic metabolites

Barbiturates may increase chloramphenicol metabolism and chloramphenicol may inhibit the metabolism of barbiturates

Barbiturates may increase the metabolism of corticosteroids, cyclosporine, disopyramide, griseofulvin, nifedipine, oral contraceptives, phenytoin, propafenone, quinidine, verapamil; dosage adjustments may be useful

Barbiturates may enhance the metabolism of methadone resulting in methadone withdrawal

Felbamate may increase phenobarbital concentrations leading to toxicity

Phenobarbital may reduce the diuretic response to furosemide; monitor

Concurrent use of phenobarbital with meperidine may result in increased CNS depression

Concurrent use of phenobarbital with primidone may result in elevated phenobarbital serum concentrations

Valproic acid inhibits the metabolism of phenobarbital resulting in elevated serum phenobarbital concentrations

Protect elixir from light; not stable in aqueous solutions; use only clear solutions; do not add to acidic solutions, precipitation may occur; I.V. form is incompatible with benzquinamide (in syringe), cephalothin, chlorpromazine, hydralazine, hydrocortisone, hydroxyzine, insulin, levorphanol, meperidine, methadone, morphine, norepinephrine, pentazocine, prochlorperazine, promazine, promethazine, ranitidine (in syringe), vancomycin

Short-acting 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.

Oral:

Onset of hypnosis: Within 20-60 minutes

Duration: 6-10 hours

I.V.:

Onset of action: Within 5 minutes

Peak effect: Within 30 minutes

Duration: 4-10 hours

Absorption: Oral: 70% to 90%

Protein binding: 20% to 45%, decreased in neonates

Metabolism: In the liver via hydroxylation and glucuronide conjugation

Half-life: Neonates: 45-500 hours; Infants: 20-133 hours; Children: 37-73 hours; Adults: 53-140 hours

Time to peak serum concentration: Oral: Within 1-6 hours

Elimination: 20% to 50% excreted unchanged in urine

Children:

Sedation: Oral: 2 mg/kg 3 times/day

Hypnotic: I.M., I.V., S.C.: 3-5 mg/kg at bedtime

Preoperative sedation: Oral, I.M., I.V.: 1-3 mg/kg 1-1.5 hours before procedure

Adults:

Sedation: Oral, I.M.: 30-120 mg/day in 2-3 divided doses

Hypnotic: Oral, I.M., I.V., S.C.: 100-320 mg at bedtime

Preoperative sedation: I.M.: 100-200 mg 1-1.5 hours before procedure

Anticonvulsant: Status epilepticus: Loading dose: I.V.:

Infants and Children: 10-20 mg/kg in a single or divided dose; in select patients may administer additional 5 mg/kg/dose every 15-30 minutes until seizure is controlled or a total dose of 40 mg/kg is reached

Adults: 300-800 mg initially followed by 120-240 mg/dose at 20-minute intervals until seizures are controlled or a total dose of 1-2 g

Anticonvulsant maintenance dose: Oral, I.V.:

Infants: 5-8 mg/kg/day in 1-2 divided doses

Children:

1-5 years: 6-8 mg/kg/day in 1-2 divided doses

5-12 years: 4-6 mg/kg/day in 1-2 divided doses

Children >12 years and Adults: 1-3 mg/kg/day in divided doses or 50-100 mg 2-3 times/day

Withdrawal: Initial daily requirement is determined by substituting phenobarbital 30 mg for every 100 mg pentobarbital used during tolerance testing; then daily requirement is decreased by 10% of initial dose

Dosing interval in renal impairment: Cl_cr <10 mL/minute: Administer every 12-16 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

Dosing adjustment/comments in hepatic disease: Increased side effects may occur in severe liver disease; monitor plasma levels and adjust dose accordingly

Alcohol: Additive CNS effect, avoid use

Food:

Protein-deficient diets: Increases duration of action of barbiturates. Should not restrict or delete protein from diet unless discussed with physician. Be consistent with protein intake during therapy with barbiturates.

Fresh fruits containing vitamin C: Displaces drug from binding sites, resulting in increased urinary excretion of barbiturate. Educate patients regarding the potential for a decreased anticonvulsant effect of barbiturates with consumption of foods high in vitamin C.

Vitamin D: Loss in vitamin D due to malabsorption; increase intake of foods rich in vitamin D. Supplementation of vitamin D may be necessary.

Phenobarbital serum concentrations, mental status, CBC, LFTs, seizure activity

Therapeutic:

Infants and children: 15-30 mg/mL (SI: 65-129 mmol/L)

Adults: 20-40 mg/mL (SI: 86-172 mmol/L)

Toxic: >40 mg/mL (SI: >172 mmol/L)

Toxic concentration: Slowness, ataxia, nystagmus: 35-80 mg/mL (SI: 150-344 mmol/L)

Coma with reflexes: 65-117 mg/mL (SI: 279-502 mmol/L)

Coma without reflexes: >100 mg/mL (SI: >430 mmol/L)

ammonia (B); bilirubin (S), copper (S), assay interference of LDH, LFTs

No information available to require special precautions

No effects or complications reported

I.V./I.M.: Patient instructions and information are determined by patient condition and therapeutic purpose. If self-administered, use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. While using this medication, do not use alcohol and 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, vomiting, or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help). Report skin rash or irritation; CNS changes (confusion, depression, increased sedation, excitation, headache, insomnia, or nightmares); difficulty breathing or shortness of breath; changes in urinary pattern or menstrual pattern; muscle weakness or tremors; or difficulty swallowing or feeling of tightness in throat. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

Parenteral solutions are highly alkaline; avoid extravasation; institute safety measures to avoid injuries; observe patient for excessive sedation and respiratory depression

Capsule: 16 mg

Elixir: 15 mg/5 mL (5 mL, 10 mL, 20 mL); 20 mg/5 mL (3.75 mL, 5 mL, 7.5 mL, 120 mL, 473 mL, 946 mL, 4000 mL)

Injection, as sodium: 30 mg/mL (1 mL); 60 mg/mL (1 mL); 65 mg/mL (1 mL); 130 mg/mL (1 mL)

Powder for injection: 120 mg

Tablet: 8 mg, 15 mg, 16 mg, 30 mg, 32 mg, 60 mg, 65 mg, 100 mg

Amitai Y and Degani Y, "Treatment of Phenobarbital Poisoning With Multiple Dose of Activated Charcoal in an Infant," J Emerg Med, 1990, 8(4):449-50.

Jacobsen D, Wiik-Larsen E, Dahl T, et al, "Pharmacokinetic Evaluation of Haemoperfusion in Phenobarbital Poisoning," Eur J Clin Pharmacol, 1984, 26(1):109-12.

Lin JL and Jeng LB, "Critical, Acutely Poisoned Patients Treated With Continuous Arteriovenous Hemoperfusion in the Emergency Department," Ann Emerg Med, 1995, 25(1):75-80.

Mockli G, Crowley M, Stern R, et al, "Massive Hepatic Necrosis in a Child After Administration of Phenobarbital," Am J Gastroenterol, 1989, 84(7):820-2.

Pond SM, Olson KR, Osterloh JD, et al, "Randomized Study of the Treatment of Phenobarbital Overdose With Repeated Doses of Activated Charcoal," JAMA, 1984, 251(23):3104-8.