phenobarbital
Bellatal, Solfoton

phenobarbital sodium
Luminal Sodium

Available forms
Available by prescription only
Capsules: 16 mg
Elixir: 15 mg/5 ml; 20 mg/5 ml
Injection: 30 mg/ml, 60 mg/ml, 65 mg/ml, 130 mg/ml
Tablets: 15 mg, 16 mg, 16.2 mg, 30 mg, 60 mg, 90 mg, 100 mg

Indications and dosages
 All forms of epilepsy except absence seizures, febrile seizures in children. Adults: 60 to 100 mg P.O. daily, divided t.i.d. or given as single dose h.s. Or, give 200 to 300 mg I.M. or I.V. and repeat q 6 hours, p.r.n.
Children: 1 to 6 mg/kg P.O. daily, usually divided q 12 hours. It can, however, be administered once daily. Or give 4 to 6 mg/kg I.V. or I.M. daily and monitor patient’s blood levels.
 Status epilepticus. Adults and children: 10 to 20 mg/kg I.V. over 10 to 15 minutes (don’t exceed 60 mg/minute). Repeat if needed.
 Sedation. Adults: 30 to 120 mg P.O., I.M., or I.V. daily in two or three divided doses. Maximum dose is 400 mg/24 hours.
Children: 8 to 32 mg P.O. daily.
 Insomnia. Adults: 100 to 200 mg P.O. or 100 to 320 mg I.M.
 Preoperative sedation. Adults: 100 to 200 mg I.M. 60 to 90 minutes before surgery.
Children: 1 to 3 mg/kg I.V. or I.M. 60 to 90 minutes before surgery.
 Drug withdrawal. Adults: 30 mg P.O. in three or four divided doses for each 100 to 200 mg of the barbiturate or nonbarbiturate hypnotic that patient has been taking daily. If patient shows signs of withdrawal on the first day, a loading dose of 100 to 200 mg may be administered I.M.
Infants: 3 to 10 mg/kg/day P.O. Gradually decrease over a 2-week period.

Pharmacodynamics
Anticonvulsant action: Exact cellular site and mechanism of action unknown. Suppresses spread of seizure activity produced by epileptogenic foci in the cortex, thalamus, and limbic systems by enhancing the effect of GABA. Both presynaptic and postsynaptic excitability are decreased; also raises the seizure threshold.
Sedative-hypnotic action: Acts throughout the CNS as a nonselective depressant with a slow onset of action and a long duration of action. Particularly sensitive to this drug is the reticular activating system, which controls CNS arousal. Phenobarbital decreases both presynaptic and postsynaptic membrane excitability by facilitating the action of GABA.

Pharmacokinetics
Absorption: Well absorbed after oral administration, with 70% to 90% reaching bloodstream. 100% absorption after I.M. administration. After oral administration, serum levels peak in 1 to 2 hours; levels in CNS peak at 1 to 3 hours. Serum level of 10 mcg/ml needed to produce sedation; 40 mcg/ml usually produces sleep. Levels of 20 to 40 mcg/ml considered therapeutic for anticonvulsant therapy.
Distribution: Distributed widely throughout body. About 25% to 30% protein-bound.
Metabolism: Metabolized by hepatic microsomal enzyme system.
Excretion: 25% to 50% of dose eliminated unchanged in urine; remainder excreted as metabolites of glucuronic acid. Drug’s half-life is 5 to 7 days.

Contraindications and precautions
Contraindicated in patients with barbiturate hypersensitivity or history of manifest or latent porphyria, hepatic dysfunction, respiratory disease with dyspnea or obstruction, or nephritis.
  Use cautiously in elderly or debilitated patients and in those with acute or chronic pain, depression, suicidal tendencies, history of drug abuse, blood pressure alterations, CV disease, shock, or uremia.

Interactions
Drug-drug. Antidepressants, antihistamines, narcotics, phenothiazines, tranquilizers, other sedative-hypnotics: Potentiates CNS and respiratory depressant effects. Monitor patient closely.
Corticosteroids, digitoxin, doxycycline, hormonal contraceptives (and other estrogens), theophylline (and other xanthines): Enhances hepatic metabolism of these drugs. Monitor patient for clinical effectiveness; adjust dosage as needed.
Disulfiram, MAO inhibitors, valproic acid: Decreases metabolism of phenobarbital and increases toxicity. Monitor serum levels.
Griseofulvin: Decreases absorption from GI tract. Separate administration times by at least 2 hours.
Rifampin: Decreases phenobarbital levels because of increased hepatic metabolism. Monitor serum levels; adjust dosage as needed.
Warfarin, other oral anticoagulants: Enhances enzymatic degradation of these drugs. Increased dosages of anticoagulant may be needed.
Drug-herb. Evening primrose oil: May increase anticonvulsant requirement. Discourage use together.
Drug-lifestyle. Alcohol use: Potentiates CNS and respiratory depressant effects. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, lethargy, hangover, paradoxical excitement in elderly patients, somnolence, change in EEG patterns.
CV: bradycardia, hypotension, thrombophlebitis.
GI: nausea, vomiting.
Hematologic: exacerbation of porphyria.
Respiratory: respiratory depression, apnea.
Skin: rash, erythema multiforme, Stevens-Johnson syndrome, urticaria, pain, swelling, necrosis, nerve injury at injection site.
Other: angioedema, physical and psychological dependence.

Effects on lab test results
• May decrease bilirubin level.

Overdose and treatment
Toxicity may cause unsteady gait, slurred speech, sustained nystagmus, somnolence, confusion, respiratory depression, pulmonary edema, areflexia, and coma. Typical shock syndrome with tachycardia and hypotension along with jaundice, oliguria, and chills followed by fever may occur.
 Treatment aims to maintain and support ventilation and pulmonary function as needed; and to support cardiac function and circulation with vasopressors and IV fluids as needed. If patient is conscious and gag reflex is intact, induce emesis (if ingestion was recent) by administering ipecac syrup. If emesis is contraindicated, perform gastric lavage while a cuffed endotracheal tube is in place to prevent aspiration. Follow with administration of activated charcoal or sodium chloride cathartic. Measure intake and output, vital signs and laboratory parameters. Maintain body temperature.
 Alkalinization of urine may be helpful in removing drug from body; hemodialysis may be useful in severe overdose. Oral activated charcoal may enhance drug elimination regardless of its route of administration.

Special considerations
• Oral solution may be mixed with water or juice to improve taste.
• Don’t crush or break extended-release form; this will impair drug action.
• Reconstitute powder for injection with 2.5 to 5 ml sterile water for injection. Roll vial in hands; don’t shake.
• Use a larger vein for I.V. administration to prevent extravasation.
• Avoid I.V. administration at more than 60 mg/minute to prevent hypotension and respiratory depression. It may take up to 30 minutes after I.V. administration to achieve maximum effect.
• Administer parenteral dose within 30 minutes of reconstitution because drug hydrolyzes in solution and on exposure to air.
• Keep emergency resuscitation equipment on hand when administering phenobarbital I.V.
• Administer I.M. dose deep into large muscle mass to prevent tissue injury.
• Don’t use injectable solution if it contains a precipitate.
• Administration of full loading doses over short periods of time to treat status epilepticus will require ventilatory support in adults.
• Full therapeutic effects aren’t seen for 2 to 3 weeks, except when loading dose is used.
• Drug may cause a false-positive phentolamine test. Physiologic drug effect may impair absorption of cyanocobalamin Co 57; it may decrease serum bilirubin levels in neonates, epileptics, and patients with congenital nonhemolytic unconjugated hyperbilirubinemia. Barbiturates may increase sulfobromophthalein retention.
Breast-feeding patients
• Drug appears in breast milk. Avoid use in breast-feeding women.
Pediatric patients
• Paradoxical hyperexcitability may occur in children. Use cautiously.
Geriatric patients
• Elderly patients are more sensitive to drug’s effects and usually need lower doses. Confusion, disorientation, and excitability may occur in elderly patients.

Patient education
• Advise patient of potential for physical and psychological dependence with prolonged use.
• Warn patient to avoid alcohol and other CNS depressants while taking drug. An excessive depressant effect is possible even if drug is taken the evening before alcohol ingestion.
• Caution patient not to stop taking drug suddenly because this could cause a withdrawal reaction.
• Advise patient to avoid driving and other hazardous activities that require alertness until adverse CNS effects of drug are known.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use