Phenobarbital

Antiepileptics. Barbiturates

ATC code: N03AA02

Brand names: Phenobarbital sodium, Luminal, Solfoton

Updated 24 Sep 2026 · Methodology

Indications

Neonatal seizures

First line

Phenobarbital remains the first-line drug for neonatal seizures per international and Russian guidelines. Loading dose 20 mg/kg IV; if seizures persist, additional 10 mg/kg. Maintenance dose 3–5 mg/kg/day. Seizure control 40–60%; if ineffective, add phenytoin or levetiracetam. includes phenobarbital in the Essential Medicines List for neonatal seizure treatment.

After seizure control, gradually transition to long-term antiepileptics with better neurodevelopmental profile (levetiracetam, lamotrigine).

Sources

ICD-10: P90 · ICD-11: KB06

Status epilepticus

Second line

Phenobarbital is used in status epilepticus in resource-limited settings when modern second-line drugs (fosphenytoin, valproate, levetiracetam) are unavailable. 2016 and Essential Medicines List support this. Dose 15–20 mg/kg IV slowly. For refractory status, high-dose phenobarbital (barbiturate coma) is a third-line option in critical care.

Sources

ICD-10: G41 · ICD-11: 8A66

Focal epilepsy

Third line

Phenobarbital retains efficacy in focal and generalized epilepsy in adults. NG217 and ILAE do not list phenobarbital as first-line due to pronounced sedative and cognitive effects, plus dependence risk. Used as reserve in cases refractory to first- and second-line agents. In resource-limited countries and the Essential Medicines List, it retains a role as a basic antiepileptic.

Sources

ICD-10: G40.2 · ICD-11: 8A60

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Acute anxiety, short-term treatment

Not recommended

Use of phenobarbital and combination products containing it (Corvalol, Valocordin, Barboval) for anxiety, insomnia, or cardiovascular symptoms is not supported by international guidelines. Barbiturates were displaced by benzodiazepines in the 1970s due to a narrower therapeutic index and high dependence risk. Long-term regular use of Corvalol and similar products leads to physical dependence, withdrawal with seizures and psychosis, and bromide accumulation (bromism). In the EU these combinations are banned or regulated as prescription psychoactive substances.

Corvalol and Valocordin are sold over-the-counter in Russia, and their regular use remains a common cause of dependence and toxicity.

Sources

ICD-10: F41.9 · ICD-11: 6B0Z

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Allosterically enhances GABA-A signaling, prolongs chloride channel opening. Essential Medicines List for epilepsy, especially in resource-limited settings. Replaced by newer antiepileptics in developed countries due to sedation and CYP induction. In Russia, present in combination OTC sedatives (Corvalol, Valocordin) – chronic use causes dependence and cognitive impairment.

Safety

Contraindications

Hypersensitivity to barbiturates
Severe respiratory insufficiency
Severe hepatic impairment
Acute intermittent porphyria
History of substance use disorder
Intra-arterial administration
Subcutaneous administration (necrosis risk)

Serious adverse effects

Physical dependence with courses over 4–6 weeks
Severe withdrawal with seizures, delirium, risk of fatality
Respiratory and circulatory depression in overdose
Hepatotoxicity (rare)
Teratogenicity: cleft palate, cardiac defects, digital hypoplasia, reduced neurocognitive development

Common adverse effects

Sedation, drowsiness, fatigue
Incoordination, dizziness
Cognitive impairment, especially in children and elderly
Paradoxical excitement in children
Depressed mood

Uncommon adverse effects

DRESS syndrome
Vitamin D deficiency and osteomalacia
Dupuytren contracture
Bone marrow suppression
Hepatotoxicity

Pregnancy: can you take Phenobarbital?

AEMPS summary of product characteristics (section 4.6): women of childbearing potential should use highly effective contraception during phenobarbital treatment and for 2 months after the last dose, and not rely on oral hormonal contraceptives, whose effect phenobarbital can reduce through enzyme induction. Phenobarbital monotherapy is associated with a higher risk of major congenital malformations (cleft lip and palate, cardiovascular malformations), about 2 to 3 times the background rate of 2–3% in the general population; the risk is dose-dependent and no risk-free dose has been found, and hypospadias, facial dysmorphism, neural tube defects, microcephaly, digital anomalies, small-for-gestational-age babies and neurodevelopmental disorders have also been reported. Phenobarbital should not be used in pregnancy unless the potential benefit outweighs the risks and alternatives have been considered; if there is no alternative, the lowest effective dose is used, as monotherapy where possible, with folic acid before conception and during pregnancy, and treatment is not stopped abruptly because of the risk of seizures. After third-trimester use, newborns may show sedation, hypotonia and sucking problems; in infants of treated mothers, withdrawal with seizures or hyperreactivity (at birth or up to 14 days later) and bleeding in the first 24 hours of life have been reported. To prevent bleeding, the mother takes oral vitamin K1 10 to 20 mg a day in the month before delivery, and the newborn receives 1 to 10 mg intravenously at birth.

Breastfeeding: can you take Phenobarbital?

Passes into breast milk at 36–100% of maternal plasma level. LactMed advises caution and infant monitoring (sedation, poor feeding). Breastfeeding may need to be limited if infant develops significant symptoms.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Dose titration

For epilepsy in adults: starting dose 50–100 mg 2–3 times daily orally, maintenance 100–300 mg/day. Target plasma level 15–40 µg/mL. In children: 3–5 mg/kg/day. In neonates with seizures: loading dose 20 mg/kg IV. Due to long half-life, steady state is reached at 2–3 weeks. Once-daily dosing is sufficient in some patients.

Monitoring

Monitor plasma phenobarbital level (target 15–40 µg/mL) at 2–3 weeks after initiation, with dose changes, and when adverse effects occur. Complete blood count, liver function tests, 25(OH) vitamin D – annually with long-term therapy. In children, assess neurocognitive development. In patients on long-term therapy (over 5 years), bone mineral density.

Special situations

When discontinuing after long-term use, taper gradually by 10–25% every 2–4 weeks. Abrupt withdrawal causes severe symptoms with anxiety, insomnia, seizures, delirium, and risk of fatality. Phenobarbital is a strong CYP3A4 inducer and reduces effectiveness of oral contraceptives, warfarin, many antibiotics, and immunosuppressants. Avoid combining with alcohol, opioids, benzodiazepines without compelling indication due to severe respiratory depression risk. Regular Corvalol or Valocordin use (over 30–60 mL/day) causes dependence – this behavior requires addiction medicine consultation.

Common myths

Myth: "phenobarbital in Corvalol is safe, people have used it for heart problems for decades". Fact: regular Corvalol, Valocordin, and similar products cause physical phenobarbital dependence. Withdrawal causes anxiety, insomnia, seizures. Additionally, bromide accumulates with bromism (mental disturbances, dermatitis, tremor). For cardiac symptoms, see a cardiologist, not Corvalol.

Myth: "phenobarbital is outdated and no longer used". Fact: remains first-line for neonatal seizures. Included in Essential Medicines List.

Myth: "one can drive after Corvalol". Fact: phenobarbital and bromide impair concentration and reaction time for 24–48 hours; with regular use this effect is constant.

Drug–nutrient interactions

Vitamin D

Phenobarbital induces CYP24A1 and accelerates 25(OH) vitamin D catabolism. Long-term therapy (over 2 years) reduces vitamin D level and causes osteopenia and osteomalacia. Check 25(OH) vitamin D annually and supplement cholecalciferol 800–2000 IU/day when level falls to 30 ng/mL or below.

Source: FDA: Phenobarbital sodium injection prescribing information (2019)

Vitamin B12

Long-term phenobarbital use is associated with decreased vitamin B12 level in some patients. When symptoms appear (megaloblastic anemia, neuropathy) or serum level drops, give oral replacement 1000 µg/day.

Source: FDA: Phenobarbital sodium injection prescribing information (2019)

Vitamin K

Phenobarbital induces vitamin K catabolism. In pregnant women in the third trimester and in newborns of mothers on phenobarbital, the risk of hemorrhagic disease of the newborn is increased. Prophylaxis: mother – vitamin K1 10 mg/day orally in the last month of pregnancy; newborn – vitamin K1 1 mg IM immediately after delivery.

Source: FDA: Phenobarbital sodium injection prescribing information (2019)

Folate

Phenobarbital reduces folate level with long-term therapy through impaired absorption and accelerated metabolism. In women of reproductive age, folic acid 4–5 mg/day is recommended 1–3 months preconception to reduce neural tube defect risk. In adults on long-term therapy, 1–5 mg folic acid/day is given.

Source: FDA: Phenobarbital sodium injection prescribing information (2019)

Drug–drug interactions

1 pair found. Sorted from critical to minor.

ModerateEstradiolEstrogens — natural and semisynthetic

Mechanism

Phenobarbital is a strong CYP3A4 inducer; it lowers oestradiol levels by 40–60%. On menopausal hormone therapy, menopausal symptoms may return. On combined oral contraceptives, unplanned pregnancy risk arises.

Symptoms

Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.

Management

On menopausal hormone therapy, raise the oestradiol dose or switch to transdermal forms. For contraception on phenobarbital, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate. In young women with epilepsy, consider switching phenobarbital to levetiracetam or lamotrigine (no CYP3A4 induction).

Sources

FDA: Tegretol (carbamazepine) prescribing information (2009)

Pair details →Estradiol →

Label mentions142 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalAtazanavir
«Administración con atazanavir, saquinavir, daclatasvir, dasabuvir, dolutregravir, paritaprevir, ombitasvir, ledipasvir, simeprevir, sofosbuvir. (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
Majoranticoagulantesclass named in the label
«Anticoagulantes orales : disminuye la eficacia. Se requiere realizar monitorización frecuente del tiempo de protrombina y del INR durante el tratamiento combinado. Se debe ajustar la dosis del…»
AEMPS, section 4.5 · Open on CIMA
Majorbenzodiazepinasclass named in the label
«El riesgo de depresión respiratoria se incrementa con el uso concomitante de benzodiacepinas. Se debe tener en cuenta el efecto depresor de fenobarbital sobre la respiración. Se recomienda especial…»
AEMPS, section 4.4 · Open on CIMA
Majorcorticosteroidesclass named in the label
«Corticoides (glucocorticoides sistémicos y mineralocorticoides) : disminución de la eficacia. Las consecuencias de esta situación son particularmente significativas en pacientes con la enfermedad de…»
AEMPS, section 4.5 · Open on CIMA
MajorHydrocortisone
«Corticoides (glucocorticoides sistémicos y mineralocorticoides) : disminución de la eficacia. Las consecuencias de esta situación son particularmente significativas en pacientes con la enfermedad de…»
AEMPS, section 4.5 · Open on CIMA
MajorMethadone
«Metadona : aumento del riesgo de depresión respiratoria, la cual puede ser letal en caso de sobredosis. Además, se puede producir una disminución de las concentraciones plasmáticas de metadona con el…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantsclass named in the label
«Drug Interactions: Anticoagulants . Phenobarbital lowers the plasma levels of dicumarol and causes a decrease in anticoagulant activity as measured by the prothrombin time. Barbiturates can induce…»
FDA, section 7 · Open on DailyMed
Moderateanticonceptivos hormonalesclass named in the label
«Estroprogestágenos y progestágenos (utilizados como contraceptivos) : reducción de la eficacia del contraceptivo. Se debe considerar el uso de otros métodos anticonceptivos alternativos (ver sección…»
AEMPS, section 4.5 · Open on CIMA
Moderateantidepresivos tricíclicosclass named in the label
«Antidepresivos (incluyendo IMAOs, tricíclicos e ISRS): disminuyen el umbral de convulsión, por lo que puede favorecer la aparición de crisis convulsivas generalizadas. Se debe valorar la idoneidad…»
AEMPS, section 4.5 · Open on CIMA
ModerateCarbamazepine
«Carbamazepina: disminución gradual de las concentraciones plasmáticas de carbamazepina y de su metabolito activo, sin cambio aparente en su eficacia anticonvulsivante. Esto se debe tener en cuenta…»
AEMPS, section 4.5 · Open on CIMA
ModerateCiclosporin
«Ciclosporina, tacrolimus : por extrapolación a partir de rifampicina, puede reducir la eficacia durante el tratamiento concomitante. Las concentraciones plasmáticas deben ser monitorizadas.»
AEMPS, section 4.5 · Open on CIMA
Moderatecorticosteroidsclass named in the label
«Drug Interactions: Corticosteroids. Barbiturates appear to enhance the metabolism of exogenous corticosteroids, probably through the induction of hepatic microsomal enzymes. Patients stabilized on…»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

CriticalAtazanavir
«CONTRAINDICATIONS: Anticonvulsants Carbamazepine, phenobarbital, phenytoin»
FDA, section 4 · Open on DailyMed
CriticalCobicistat
«CONTRAINDICATIONS: Anticonvulsants: carbamazepine, phenobarbital, phenytoin»
FDA, section 4 · Open on DailyMed
CriticalRanolazine
«CONTRAINDICATIONS: CYP3A inducers (e.g., rifampin, phenobarbital, St. John’s wort) (4 , 7.1)»
FDA, section 4 · Open on DailyMed
CriticalVoriconazole
«La administración concomitante con rifampicina, carbamazepina y barbitúricos de acción prolongada p. ej., fenobarbital y hierba de San Juan (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalVoriconazole
«DRUG INTERACTIONS: Long Acting Barbiturates (e.g., phenobarbital, mephobarbital) (CYP450 Induction) Not Studied In Vivo or In Vitro , but Likely to Result in Significant Reduction Contraindicated»
FDA, section 7 · Open on DailyMed
MajorApixaban
«Inductores del CYP3A4 y de la P ‑ gp: La administración concomitante de apixabán con rifampicina, un potente inductor del CYP3A4 y de la P ‑ gp, produjo disminuciones aproximadas del 54 % y 42 % en…»
AEMPS, section 4.5 · Open on CIMA
MajorBupropion
«DRUG INTERACTIONS: • CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based…»
FDA, section 7 · Open on DailyMed
MajorDarunavir
«Darunavir potenciado con cobicistat es más sensible a la inducción del CYP3A que darunavir potenciado con ritonavir. El uso concomitante con inductores potentes de CYP3A está contraindicado, dado que…»
AEMPS, section 4.3 · Open on CIMA
MajorDronedarone
«Inductores del CYP 3A4: Rifampicina (600 mg una vez al día) disminuye los niveles de dronedarona en un 80% sin cambios importantes en los niveles de su metabolito activo. Por lo tanto, la…»
AEMPS, section 4.5 · Open on CIMA
MajorDronedarone
«Effects of Other Drugs on Dronedarone: Avoid rifampin or other CYP3A inducers such as phenobarbital, carbamazepine, phenytoin, and St. John's wort because they decrease exposure to dronedarone…»
FDA, section 7 · Open on DailyMed
MajorEplerenone
«Inductores CYP3A4: Debido al riesgo de descenso de la eficacia de eplerenona, no se recomienda el uso concomitante de inductores CYP3A4 (rifampicina, carbamazepina, fenitoína, fenobarbital, hierba de…»
AEMPS, section 4.5 · Open on CIMA
MajorExemestane
«DRUG INTERACTIONS: Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort) may significantly decrease exposure to EXEMESTANE. Dose…»
FDA, section 7 · Open on DailyMed
MajorFesoterodine
«Inductores del CYP3A4: La inducción del CYP3A4 puede llevar a niveles plasmáticos subterapéuticos. No se recomienda el uso concomitante con inductores del CYP3A4 (por ejemplo, carbamazepina…»
AEMPS, section 4.5 · Open on CIMA
MajorHydrocortisone
«Drug Interactions: The pharmacokinetic interactions listed below are potentially clinically important. Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the…»
FDA, section 7 · Open on DailyMed
MajorItraconazole
«Potencial de interacción: No se debe usar itraconazol hasta 2 semanas después de la suspensión del tratamiento con medicamentos inductores del CYP3A4 (rifampicina, rifabutina, fenobarbital…»
AEMPS, section 4.4 · Open on CIMA
MajorMethylprednisolone
«Drug Interactions: The pharmacokinetic interactions listed below are potentially clinically important. Mutual inhibition of metabolism occurs with concurrent use of cyclosporine and…»
FDA, section 7 · Open on DailyMed
MajorOxycodone
«Los medicamentos que inducen depresión respiratoria como las benzodiacepinas, el fenobarbital y otros opioides (analgésicos, antitusivos o tratamientos de sustitución) pueden aumentar el riesgo de…»
AEMPS, section 4.5 · Open on CIMA
MajorPosaconazole
«Fenitoína: Fenitoína (200 mg una vez al día) disminuyó la C máx y el AUC de posaconazol en un 41 % y un 50 %, respectivamente. Se debe evitar el uso concomitante de posaconazol con fenitoína e…»
AEMPS, section 4.5 · Open on CIMA
MajorRanolazine
«Inductores del CYP3A4: La rifampicina (600 mg una vez al día) disminuye las concentraciones de ranolazina en el estado estacionario en aproximadamente un 95%. Se debe evitar iniciar un tratamiento…»
AEMPS, section 4.5 · Open on CIMA
MajorRivaroxaban
«Inductores del CYP3A4: La administración concomitante de rivaroxabán con rifampicina, un potente inductor del CYP3A4, produjo una disminución aproximada del 50% del AUC media de rivaroxabán, con…»
AEMPS, section 4.5 · Open on CIMA
MajorRoflumilast
«La administración de rifampicina, inductora de enzimas del citocromo P450, resultó en una reducción de aproximadamente un 60% de la actividad inhibidora total de la PDE4. Por lo tanto, el uso de…»
AEMPS, section 4.5 · Open on CIMA
MajorRoflumilast
«Drugs that Induce Cytochrome P450 (CYP) Enzymes: Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets…»
FDA, section 7 · Open on DailyMed
MajorSunitinib
«La administración de sunitinib con inductores potentes del CYP3A4 (por ejemplo, dexametasona, fenitoína, carbamazepina, rifampicina, fenobarbital o plantas medicinales que contienen Hierba de San…»
AEMPS, section 4.5 · Open on CIMA
MajorTicagrelor
«Inductores del CYP3A: La administración concomitante de rifampicina y ticagrelor redujo la C max y el AUC de ticagrelor en un 73% y un 86%, respectivamente. La C max del metabolito activo no varió y…»
AEMPS, section 4.5 · Open on CIMA
MajorTicagrelor
«Strong CYP3A Inducers: Strong CYP3A inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor. Avoid use with strong inducers of CYP3A (e.g., rifampin, phenytoin…»
FDA, section 7 · Open on DailyMed
MajorUlipristal acetate
«No se recomienda el uso concomitante de acetato de ulipristal con inductores de CYP3A4, debido a las interacciones (por ejemplo, barbitúricos [incluyendo primidona y fenobarbital], fenitoína…»
AEMPS, section 4.4 · Open on CIMA
ModerateBetamethasone
«Inductores e inhibidores enzimáticos: primidona, fenobarbital, rifabutina, efedrina y aminoglutetimida, pueden reducir el efecto.»
AEMPS, section 4.5 · Open on CIMA
ModerateClarithromycin
«DRUG INTERACTIONS: Alfentanil Bromocriptine Cilostazol Methylprednisole Vinblastine Phenobarbital St. John’s Wort Use With Caution There have been spontaneous or published reports of CYP3A based…»
FDA, section 7 · Open on DailyMed

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Frequently asked

What is Phenobarbital used for?

Phenobarbital is evaluated for the following indications with varying evidence strength: Status epilepticus (evidence tier A), Neonatal seizures (evidence tier A), Focal epilepsy (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Phenobarbital?

Common side effects of Phenobarbital (≥ 1 in 100): Sedation, drowsiness, fatigue, Incoordination, dizziness, Cognitive impairment, especially in children and elderly, Paradoxical excitement in children, Depressed mood. See the Safety section for uncommon and serious reactions.

Is Phenobarbital safe during pregnancy?

Is Phenobarbital compatible with breastfeeding?

Can you drink alcohol while taking Phenobarbital?

Avoid combining with alcohol, opioids, benzodiazepines without compelling indication due to severe respiratory depression risk.

Who should not take Phenobarbital?

Phenobarbital is contraindicated in: Hypersensitivity to barbiturates; Severe respiratory insufficiency; Severe hepatic impairment; Acute intermittent porphyria; History of substance use disorder. Full list in the Safety section.

phenobarbital in Corvalol is safe, people have used it for heart problems for decades

regular Corvalol, Valocordin, and similar products cause physical phenobarbital dependence. Withdrawal causes anxiety, insomnia, seizures. Additionally, bromide accumulates with bromism (mental disturbances, dermatitis, tremor). For cardiac symptoms, see a cardiologist, not Corvalol.

phenobarbital is outdated and no longer used

remains first-line for neonatal seizures. Included in WHO Essential Medicines List.

one can drive after Corvalol

phenobarbital and bromide impair concentration and reaction time for 24–48 hours; with regular use this effect is constant.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 07/01/2025
FDA / DailyMedLabel dated 06/11/2026
GRLS

Other drugs in this group

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