Luminal

General

• Adjust dosage carefully and slowly according to individual requirements and response.a b

• Following chronic administration, withdraw phenobarbital slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.a d

• To prevent rebound in rapid eye movement (REM) sleep, withdrawal of a single therapeutic dose over 5 or 6 days (e.g., reducing dosage from 3 to 2 doses daily for 1 week) has been recommended when barbiturates are discontinued following prolonged use.a

Seizures

• 2–3 weeks of therapy may be required to achieve full anticonvulsant effects.b

• When transferring a patient to another anticonvulsant drug, reduce phenobarbital dosage gradually over 1 week while, at the same time, instituting therapy with a low dose of the replacement drug.b

• Withdraw phenobarbital or reduce dosage slowly to avoid precipitating seizures or status epilepticus.b

Insomnia

• Do not administer for periods >2 weeks.a

Administration

Administer orally or by IM or slow IV injection.a b c d Sub-Q injection not recommended.a d

Oral Administration

Frequently administered in 2 or 3 divided doses;a however, there is no advantage in dividing the daily dosage (because of the long half-life).a b

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Reserve IV administration for emergency treatment of acute seizure states; however, usefulness in these conditions is limited.a b (See Seizure Disorders under Uses.)

Patient should be hospitalized and under close supervision.a

To minimize the risk of irritation and thrombosis, do not use small veins (e.g., those on the dorsum of the hands or wrist).d

Avoid intra-arterial injection.b (See Intra-arterial Injection under Cautions.)

≤60 mg/minute.a b d

IM Administration

Maximum volume of single injections is 5 mL; administer deeply into a large muscle to avoid tissue irritation.d

Dosage

Available as phenobarbital sodium; dosage expressed in terms of the salt.d

Pediatric Patients

6 mg/kg daily or 180 mg/m2 daily, in 3 equally divided doses.a c

1–3 mg/kg preoperatively.a d

16–100 mg administered 60–90 minutes before surgery;a alternatively, 1–3 mg/kg preoperatively.a d

Infants: 3–10 mg/kg daily.a After symptoms are relieved, decrease dosage gradually and withdraw drug completely over a 2-week period.a

15–50 mg 2 or 3 times daily.c Alternatively, 3–5 mg/kg or 125 mg/m2 daily.b

4–6 mg/kg daily for 7–10 days to reach therapeutic blood concentrations; alternatively, 10–15 mg/kg daily.d

3–4 mg/kg daily.b

15–20 mg/kg IV over 10–15 minutes.d Alternatively 100–400 mg IM or IV; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).b

7 mg/kg per day from the first to fifth day of life.a

5 mg/kg IM on the first day of life, followed by 5 mg/kg orally on the second to seventh day.a

Children <12 years of age: Dosages of 3–12 mg/kg daily in 2 or 3 divided doses have been used.a

Adults

30–120 mg daily.c

100–320 mg.c

100–320 mg.c d

30-mg dose for each 100- to 200-mg dose of the barbiturate or nonbarbiturate hypnotic that the patient has been taking daily, administered in 3 or 4 divided doses.a If the patient shows signs of withdrawal on the first day, a loading dose of 100–200 mg of phenobarbital sodium may be administered IM in addition to the oral dose.a

After stabilization on phenobarbital sodium, decrease the total daily dose of phenobarbital sodium by 30 mg per day.a After withdrawal symptoms are relieved, gradually decrease dosage and withdraw completely over a 2-week period.a

100–200 mg given 60–90 minutes before surgery.a d

100–300 mg daily,b c usually at bedtime.b

20–320 mg; repeat in 6 hours, if necessary.d Alternatively, 200–600 mg; allow up to 30 minutes for maximum anticonvulsant effect before administering additional doses (to prevent overdosage).b

Some clinicians administer phenobarbital sodium IV until seizures stop or a total dose of 20 mg/kg has been given.a b Discontinue IV injections as soon as the desired effect is obtained.b

Dosages of 90–180 mg daily in 2 or 3 divided doses have been used.a

Special Populations

Hepatic Impairment

Dosage reduction recommended in patients with hepatic impairment;c d e avoid use in patients with marked hepatic impairment.c d

Renal Impairment

Dosage reduction recommended.d e

Geriatric Patients

Dosage reduction recommended.d e f

Contraindications

• Known hypersensitivity to any barbiturates.c d

• Respiratory disease in which dyspnea or obstruction is evident.c d

• Marked impairment of hepatic function.c d

• History of manifest or latent porphyriac d (due to potential for exacerbation of acute intermittent porphyria or porphyria variegata).f

• Previous addiction to sedative and/or hypnotic drugs.c d

Warnings/Precautions

Warnings

Potential for paradoxical excitement and/or euphoria, restlessness, or delirium in patients with severe pain.f Barbiturates could mask important symptoms in patients with acute or chronic pain.d f Use with caution in such patients.d f Should not be used to relieve pain or to produce sedation or sleep in the presence of uncontrolled pain.c f

Possible tolerance, psychologic dependence, and physical dependence.c d (See Contraindications under Cautions.)

Abrupt cessation after prolonged use in dependent individuals may result in withdrawal symptoms (e.g., delirium, convulsions) and potentially be fatal.c d Drug must be withdrawn gradually in patients receiving excessive dosages over extended periods of time.d

Performance of activities requiring mental alertness and physical coordination may be impaired.c d

Concurrent use of other CNS depressants may potentiate CNS depression.c d (See Specific Drugs under Interactions.)

Possible respiratory depression, apnea, laryngospasm, hypertension, or vasodilation and hypotension, particularly if phenobarbital is administered IV too rapidly.d f Administer slowly; personnel and equipment should be readily available for administration of artificial respiration.d f

Sensitivity Reactions

Exfoliative dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), sometimes fatal, reported rarely.b c d Because skin eruptions can precede potentially fatal reactions, discontinue phenobarbital whenever dermatologic reactions occur.d f

Hypersensitivity reactions (e.g., localized swelling, particularly of the eyelids, cheeks, or lips; erythematous dermatitis) may occur, particularly in patients with a history of asthma, urticaria, or angioedema.c

General Precautions

Inadvertent intra-arterial administration can cause spasm and severe pain along the affected artery, resulting in local reactions varying in severity from transient pain to gangrene.d

Discontinue injection if the patient complains of pain or if signs of inadvertent intra-arterial injection (e.g., patches of discolored skin, a white hand with cyanosed skin, delayed onset of action) occur.b d Appropriate therapy for such inadvertent injection has not been fully established; consult manufacturers’ labeling for current recommendations.b d

Use with caution, if at all, in depressed patients; potential for suicidal tendencies.c d f Prescribe drug in the smallest feasible quantity.c

Use parenterally with extreme caution in debilitated patients or patients with severe hepatic impairment, pulmonary or cardiac disease, status asthmaticus, uremia, or shock.d f

Specific Populations

Tablets: Category B.c Injection: Category D.d

Barbiturates have caused postpartum hemorrhage and hemorrhagic disease in neonates; readily reversible with vitamin K therapy.f i

Possible withdrawal symptoms in neonates born to women who received barbiturates throughout the last trimester of pregnancy.f Premature neonates are particularly susceptible to the depressant effects of barbiturates.f

Distributed into milk; use with caution.c d

May produce paradoxical excitement and hyperactivity or exacerbate existing hyperactivity; if severe, substitute another barbiturate or therapeutic agent.b

Possible behavioral (e.g., hyperactivity, fussiness, lethargy, disturbed sleep, irritability, disobedience, stubbornness, depressive symptoms) or cognitive effects (e.g., deficits on neuropsychiatric tests, impaired short-term memory and memory concentration tasks) associated with anticonvulsant use.d i If such changes occur and alternative causes are not readily evident, consider the possibility that anticonvulsant therapy may be responsible and the need for dosage reduction or substitution of alternative anticonvulsant(s).i

Phenobarbital sodium injection contains benzyl alcohol.d Manufacturer does not recommend use in neonates;d AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.h

Possible increased sensitivity to barbiturates.d Geriatric patients may frequently react to barbiturates with excitement, confusion, or depression.c f

Use with caution; should not be used in patients with marked hepatic impairment.c d (See Contraindications under Cautions.)

Use with extreme caution in patients with nephritis.b d Use parenterally with extreme caution in patients with uremia.d f

Common Adverse Effects

Residual sedation, drowsiness, lethargy, vertigo, nausea, vomiting, headache.c d f

• CNS effects appear to be related, at least partially, to the drug’s ability to enhance activity of GABA, the principal inhibitory neurotransmitter in the CNS,104 105 106 107 108 by altering inhibitory synaptic transmissions that are mediated by GABAA receptors.105 106 108

• Capable of producing all levels of CNS depressionfrom mild sedation to hypnosis to deep coma to death.c d

• Anticonvulsant effects of barbiturates are multiple and rather nonselective.i Principal mechanism of action appears to be reduction of monosynaptic and polysynaptic transmission resulting in decreased excitability of the entire nerve cell; barbiturates also increase the threshold for electrical stimulation of the motor cortex.i

• Barbiturates lower serum bilirubin concentrations in neonates and patients with congenital nonhemolytic unconjugated hyperbilirubinemia, presumably by induction of glucuronyl transferase, the enzyme that conjugates bilirubin.f

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Applies to phenobarbital: oral elixir, oral tablets, parenteral injection

Side effects include:

Residual sedation, drowsiness, lethargy, vertigo, nausea, vomiting, headache.

Daytime Sedation:
30 to 120 mg orally, IM, or IV in 2 or 3 divided doses
Maximum dose: 400 mg during a 24-hour period

Preoperative Sedation:
Parenteral:
100 to 200 mg IM 60 to 90 minutes before surgery

Comments:
-Frequency of administration should be determined by the patient response.
-Parenteral administration should be reserved for situations in which oral administration is impossible/impractical.

Uses: Daytime sedation; preoperative sedation

Acute Convulsions
Parenteral:
20 to 320 mg IM or IV every 6 hours as necessary

Anticonvulsant:
Oral:
60 to 200 mg orally per day

Comments:
-Maintenance doses should be determined by clinical laboratory reference values.
-Prevention of febrile seizures may not influence the development of epilepsy.

Uses: Treatment of generalized and partial seizures; treatment/prophylaxis of febrile seizures

Anticonvulsant:
Oral:
-Initial dose: 15 to 20 mg/kg orally
-Recommended dose: 3 to 6 mg/kg orally

Parenteral:
4 to 6 mg/kg/day for 7 to 10 days or 5 to 15 mg/kg/day IM or IV

Status epilepticus:
Parenteral:
-Initial dose: 15 to 20 mg/kg IV over 10 to 15 minutes

Comments:
-Loading doses of 15 to 20 mg/kg are predicted to produce blood levels of approximately 20 mcg/mL after administration.
-Maintenance doses should be determined by clinical laboratory reference values.
-Prevention of febrile seizures may not influence the development of epilepsy.

Uses: Anticonvulsant used for the treatment of generalized and partial seizures, treatment/prophylaxis of febrile seizures, and treatment of status epilepticus.