EpilepsyRx

Phenobarbital

Generic phenobarbital; Sezaby (neonatal IV)

DailyMed-verified antiseizure indications

Indication / use

Label / evidence summary
Sezaby: neonatal seizures in term and preterm infants. The linked traditional oral tablet and solution labels list generalized and partial seizures but are unapproved legacy products; a DailyMed listing does not establish FDA approval.
Role
Maintenance; Rescue / acute treatment
Class
Barbiturate-site GABA-A potentiation; prolongs channel openings

Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.

Formulations & strengths

U.S. products unless another country is named. Strengths are per unit or stated volume.

Brand & formulation labels

Each link names the product and formulation it covers. Archived labels do not establish current availability.

Dosing & administration

Adult / product-specific schedule
Typically 60–200 mg/day individualized.
Pediatric
Traditional maintenance is commonly 3–6 mg/kg/day, individualized. Sezaby neonatal IV: load 20 mg/kg over 15 minutes; if needed, a second loading dose (20 mg/kg term; 10 or 20 mg/kg preterm) starts no sooner than 15 minutes after the first infusion ends; maximum total load 40 mg/kg. Maintenance begins 8–12 hours after the first load: 4.5 mg/kg/day divided as 1.5 mg/kg every 8 hours or 2.25 mg/kg every 12 hours, for up to 5 days.
Titration / repeat dosing
Individualize. Maintenance is often 60–200 mg/day in adults or 3–6 mg/kg/day in children; titrate slowly because steady state may take 2–3 weeks. Loading is a separate monitored protocol.

Practical administration

Product instructions
Sezaby: reconstitute each 100 mg vial with 10 mL 0.9% Sodium Chloride Injection, USP (10 mg/mL); infuse over 15 minutes into a large peripheral vein with neonatal cardiorespiratory monitoring. Legacy liquid/injectable products have different excipients and instructions. Oral BPI elixir contains alcohol 15%; verify the dispensed product.

Dose adjustment & concentrations

Renal impairment
Reduce/caution severe impairment.
Hepatic impairment
Reduce/caution; avoid marked impairment.
Serum reference information
15–40 mcg/mL

Safety

Boxed warning
Sezaby has boxed warnings about opioids, dependence/withdrawal with longer-than-recommended use, and abuse/misuse/addiction with unapproved adolescent/adult use. Traditional legacy products have different labeling; all can cause serious respiratory/CNS depression.
Contraindications
Barbiturate hypersensitivity; manifest/latent porphyria; marked hepatic impairment; respiratory disease with dyspnea or obstruction. Sezaby-specific contraindications: acute porphyria or hypersensitivity to phenobarbital/other barbiturates; consult the neonatal label for all precautions.
Serious precautions & monitoring
Schedule IV; sedation, respiratory depression, tolerance, dependence, and strong enzyme induction.

Common / selected adverse effects

  • Somnolence/sedation common; precise modern trial rate unavailable
  • Behavioral hyperactivity in children reported
  • Respiratory depression is dose related

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
Valproate, felbamate or cenobamatePhenobarbital concentrations rise; long half-life can cause delayed sedation, ataxia or respiratory toxicity.Monitor phenobarbital levels and clinical effects; reduce dose when indicated.
Many ASMs, prednisolone, anticoagulants and hormonal contraceptivesEnzyme induction lowers partner exposure; withdrawal can allow concentrations to rise.Review the full medication list and plan monitoring when phenobarbital starts or stops.
Opioids / benzodiazepines / alcoholAdditive CNS and respiratory depression.Minimize unnecessary combinations and monitor breathing.

Pregnancy & contraception

Fetal / neonatal risk
Phenobarbital crosses the placenta and is associated with fetal malformations. Exposure during the last trimester can cause neonatal withdrawal.
Contraception
Phenobarbital enzyme induction can reduce hormonal contraceptive effectiveness; use an effective alternative or backup method.
Pregnancy / postpartum monitoring
Monitor infants after sustained late-pregnancy exposure for withdrawal.

Clinical evidence

Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.

Extrapolation Guideline-supported off-label use

Trial summary

Study design / duration
Predates FDA efficacy-era and contemporary Phase 3 trial design; evidence comes from older controlled comparisons and clinical experience.
Primary endpoint
No single pivotal endpoint is identified in the cited source.
Results
Marketed before modern Phase 3 requirements. Controlled comparative evidence and long clinical experience support efficacy in focal and generalized tonic-clonic seizures; no single pivotal placebo-adjusted percentage exists.

Trial publications

Mechanism of action

  • GABA-A positive allosteric modulator at site(s) distinct from the benzodiazepine site. Predominantly prolongs channel openings/bursts rather than the classical benzodiazepine frequency effect.
  • At high concentrations, barbiturates can directly gate GABA-A channels and depress excitatory transmission. These concentration-dependent actions contribute to respiratory depression.
  • Clinical distinction: cumulative sedation and enzyme induction require attention; the receptor effect is not interchangeable with diazepam dosing.

Pharmacology

Adult values unless specified. Vd/F denotes apparent oral distribution volume.

Pharmacokinetics

Bioavailability
Oral absorption is essentially complete but slow (UK SmPC). IV: 100% by definition.
Elimination half-life
Adults: 53–118 hours, mean 79 (U.S. label). Children/newborns: a broad 60–180-hour range is reported; neonatal metabolism is immature and may prolong elimination.
Volume of distribution
Approximately 0.9 L/kg (UK elixir SmPC); estimates vary with age and study.
Active metabolite(s)
None known: the major para-hydroxyphenyl metabolite is inactive.
Active-metabolite half-life
Not applicable — no clinically established active metabolite.
Protein binding
20–45%
Metabolism / elimination
Hepatic CYP metabolism plus renal excretion

Adult values must not be used as neonatal PK constants. The Sezaby neonatal formulation and dosing remain product-specific.

Molecular structure

Molecular structure of Phenobarbital
Principal compound; salt and product forms may differ.
NIH PubChem structure and record ↗

Product history

Initial U.S. approval
Legacy phenobarbital products predate modern approval; Sezaby neonatal IV product approved 2022.
Market / formulation history
1912 historically
Brands
Generic phenobarbital; Sezaby (neonatal IV)
Manufacturer / marketer
Multiple generic manufacturers; Luminal is historical
Generic availability
Yes
Related drugs
Barbiturate family; primidone is partly metabolized to phenobarbital.

Sources & review status

Representative sources are selected product labels, not an exhaustive list of generic manufacturers. Consult the exact product and formulation prescribed. Brand-name package inserts are linked separately.

No original-brand approval record is linked for the legacy products. Sezaby has its own separate neonatal IV label.

Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: May 2024. This is a draft reference; final review is pending.

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