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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Other
Phenobarbital is a long-acting barbiturate and anticonvulsant used to control various types of seizures and provide short-term sedation. It works by enhancing GABA-mediated inhibition in the central nervous system.
Name
Phenobarbital
Raw Name
PHENOBARBITAL
Category
Other
Drug Count
9
Variant Count
195
Last Verified
February 17, 2026
RxCUI
198083, 198089, 312357, 312362, 198086, 199164, 199167, 199168, 702519, 198368, 312370, 1046787, 1046924, 2048017, 2624719, 2624724, 2671204, 2671207, 1046815, 1046978, 1739887
UNII
YQE403BP4D, SW9M9BB5K3, 451IFR0GXB, 03J5ZE7KA5, F2R8V82B84
About Phenobarbital
Phenobarbital is a long-acting barbiturate and anticonvulsant used to control various types of seizures and provide short-term sedation. It works by enhancing GABA-mediated inhibition in the central nervous system.
Detailed information about Phenobarbital
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Phenobarbital.
In the United States, the Food and Drug Administration (FDA) has approved Phenobarbital for the treatment of generalized tonic-clonic seizures (formerly known as grand mal seizures), partial seizures, and for the short-term treatment of insomnia (though it is rarely used for sleep today due to safer alternatives). It is also utilized in the emergency management of status epilepticus (a prolonged, life-threatening seizure) and as a sedative to relieve anxiety or tension. Phenobarbital is classified as a Schedule IV controlled substance under the Controlled Substances Act because it carries a risk of dependence and abuse.
Phenobarbital exerts its clinical effects by acting as a non-selective central nervous system (CNS) depressant. At the molecular level, it primarily targets the gamma-aminobutyric acid (GABA) type A receptor complex. GABA is the primary inhibitory neurotransmitter in the brain, responsible for reducing neuronal excitability.
When Phenobarbital binds to the GABA-A receptor, it increases the duration that the chloride ion channel remains open. By allowing more chloride ions to enter the neuron, the drug hyperpolarizes the cell membrane, making it less likely to fire an action potential. This effectively 'slows down' brain activity and raises the seizure threshold, making it harder for abnormal electrical discharges to spread across the brain. Unlike benzodiazepines, which increase the frequency of channel opening, barbiturates like Phenobarbital increase the duration, which explains their potent sedative and anticonvulsant properties. At higher concentrations, Phenobarbital may also inhibit glutamate signaling (an excitatory neurotransmitter) and block certain calcium channels, further contributing to its CNS-depressant effects.
Understanding how the body processes Phenobarbital is crucial for safe administration, as the drug has a very long half-life and a narrow therapeutic index (the margin between a safe dose and a toxic dose).
Your healthcare provider may prescribe Phenobarbital for several FDA-approved and off-label indications:
Phenobarbital is available in several formulations to accommodate different clinical needs:
> Important: Only your healthcare provider can determine if Phenobarbital is right for your specific condition. Regular blood tests are often required to monitor the level of medication in your system.
Dosage must be highly individualized based on the patient's clinical response, age, and blood levels of the drug. The following are typical ranges:
Phenobarbital is frequently used in children, but doses must be calculated carefully based on body weight:
Because a significant portion of Phenobarbital is excreted unchanged by the kidneys, patients with impaired renal function (kidney disease) require lower doses. Healthcare providers may increase the interval between doses or reduce the total daily amount to prevent toxic accumulation.
Since the liver is the primary site of metabolism, patients with cirrhosis or hepatitis are at high risk for toxicity. Phenobarbital should be used with extreme caution in these patients, and in cases of severe hepatic impairment, it is often contraindicated (should not be used).
Older adults are generally more sensitive to the sedative effects of barbiturates. According to the Beers Criteria (a guide for safe medication use in seniors), Phenobarbital should generally be avoided in the elderly due to the high risk of falls, confusion, and prolonged sedation. If used, doses should start at the lowest possible range.
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Never double the dose to catch up, as this significantly increases the risk of toxicity and respiratory depression.
An overdose of Phenobarbital is a medical emergency. Signs include:
If an overdose is suspected, call 911 or your local emergency services immediately. Emergency treatment often involves respiratory support (ventilator), intravenous fluids, and sometimes 'urinary alkalinization' to help the kidneys clear the drug faster.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as sudden discontinuation can trigger severe seizures.
Phenobarbital is a potent CNS depressant, and most patients will experience some degree of side effects, especially during the first few weeks of treatment. Common reactions include:
> Warning: Stop taking Phenobarbital and call your doctor immediately if you experience any of the following:
Prolonged use of Phenobarbital (months to years) is associated with specific risks:
While Phenobarbital does not always carry a specific 'Black Box' warning on all generic labels, the FDA requires a general warning for all antiepileptic drugs (AEDs) regarding the risk of Suicidal Ideation and Behavior. Data from 199 clinical trials showed that patients taking AEDs had about twice the risk of suicidal thinking compared to patients taking a placebo. This risk can appear as early as one week after starting the medication.
Report any unusual symptoms or changes in behavior to your healthcare provider immediately.
Phenobarbital is a high-alert medication that requires careful management. Patients must be aware that this drug significantly impairs mental alertness and physical coordination. Activities requiring high concentration, such as driving or operating heavy machinery, should be avoided until you know exactly how the medication affects you. Furthermore, Phenobarbital has a very narrow therapeutic range, meaning the difference between a helpful dose and a dangerous one is small.
As noted in the side effects section, the primary class-wide warning for Phenobarbital involves Suicidality. Healthcare providers must monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Families and caregivers should be alerted to the need for close observation.
To ensure safety and efficacy, your doctor will likely order the following tests:
Due to its long half-life and sedative properties, Phenobarbital causes significant psychomotor impairment. This effect is often more pronounced in the morning if the drug was taken the night before. Patients are generally advised not to drive until they have been on a stable dose for a significant period and their doctor confirms it is safe.
Do not drink alcohol while taking Phenobarbital. Alcohol is also a CNS depressant. Combining the two can lead to additive effects, resulting in severe respiratory depression, profound sedation, coma, or death. Even small amounts of alcohol can significantly increase the impairment caused by Phenobarbital.
Never stop taking Phenobarbital abruptly. Sudden withdrawal can cause 'status epilepticus'—continuous, life-threatening seizures. It can also cause a severe withdrawal syndrome characterized by tremors, hallucinations, delirium, and seizures. If the drug needs to be stopped, your doctor will provide a tapering schedule to slowly reduce the dose over several weeks or months.
> Important: Discuss all your medical conditions, especially any history of depression or substance abuse, with your healthcare provider before starting Phenobarbital.
Phenobarbital should never be used with certain medications due to the risk of life-threatening interactions:
Phenobarbital is a potent inducer of several liver enzymes (CYP3A4, CYP2C9, CYP2C19). This means it 'turns on' the liver's machinery to break down other drugs, often making them less effective:
Phenobarbital can interfere with certain diagnostic tests:
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. Phenobarbital is one of the most 'interactive' drugs in medicine, and changes to any part of your regimen can be dangerous.
There are specific conditions where the risks of Phenobarbital use far outweigh any potential benefits. In these cases, the drug must never be used:
In these situations, Phenobarbital should only be used if no other options are available, and with extreme caution:
Patients who are allergic to Primidone (which is metabolized into Phenobarbital in the body) will almost certainly be allergic to Phenobarbital. There is also a known risk of cross-sensitivity between Phenobarbital and other aromatic anticonvulsants like phenytoin and carbamazepine regarding severe skin reactions (SJS/TEN). If you have reacted to one, notify your doctor immediately before starting another.
> Important: Your healthcare provider will evaluate your complete medical history before prescribing Phenobarbital. Ensure you disclose all past allergies and chronic health conditions.
Phenobarbital is classified as FDA Pregnancy Category D. This means there is clear evidence of human fetal risk based on adverse reaction data, but the potential benefits may warrant use of the drug in pregnant women in certain life-threatening situations.
Phenobarbital passes into breast milk in significant quantities. Because the drug is cleared very slowly by infants, it can accumulate and cause profound sedation, poor feeding, and weight loss in the nursing baby. Breastfeeding is generally not recommended while taking Phenobarbital unless specifically directed by a specialist who can monitor the infant closely.
Phenobarbital is a mainstay of treatment for neonatal seizures. However, in older children, it is often associated with behavioral side effects, including hyperactivity, irritability, and decreased cognitive performance in school. Long-term use in children also requires monitoring of bone health due to the risk of rickets (softening of bones).
Elderly patients (65 and older) are at significantly higher risk for adverse effects. The drug’s long half-life means it stays in their system much longer than in younger adults.
In patients with a Glomerular Filtration Rate (GFR) less than 10 mL/min, the interval between doses should be increased (e.g., every 12-16 hours instead of every 8-12). Phenobarbital is removed by hemodialysis; therefore, a supplemental dose may be required after a dialysis session to maintain therapeutic levels.
For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B), a dose reduction of 25% to 50% is typically recommended. In Class C (severe) impairment, the drug should generally be avoided due to the risk of precipitating hepatic encephalopathy.
> Important: Special populations require individualized medical assessment and frequent monitoring of blood levels.
Phenobarbital is a sedative-hypnotic and anticonvulsant that acts as a positive allosteric modulator of the GABA-A receptor. The GABA-A receptor is a ligand-gated chloride channel. When GABA (the neurotransmitter) binds to the receptor, the channel opens. Phenobarbital binds to a distinct site on the receptor (the barbiturate binding site) and increases the duration of time the chloride channel remains open. This influx of chloride ions leads to hyperpolarization of the postsynaptic neuron, making it less responsive to excitatory stimuli. At higher doses, Phenobarbital can also directly open the chloride channel even in the absence of GABA and may inhibit excitatory AMPA receptors.
| Parameter | Value |
|---|---|
| Bioavailability | 70% - 90% (Oral) |
| Protein Binding | 20% - 45% |
| Half-life | 53 - 118 hours (Adults); 60 - 180 hours (Neonates) |
| Tmax | 8 - 12 hours (Oral) |
| Metabolism | Hepatic (Primary: CYP2C9; Secondary: CYP2C19, 2E1) |
| Excretion | Renal (25% - 50% unchanged); Fecal (minimal) |
Phenobarbital is the prototypical long-acting barbiturate. While it shares a class with drugs like pentobarbital (short-acting) and secobarbital (intermediate-acting), its specific phenyl group at the 5-position confers its unique anticonvulsant properties at doses that are not necessarily anesthetic.
Medications containing this ingredient
Common questions about Phenobarbital
Phenobarbital is primarily used as an anticonvulsant to control various types of seizures, including generalized tonic-clonic and partial seizures. It is also used in hospital settings to treat status epilepticus, a condition involving prolonged, life-threatening seizures. Beyond epilepsy, it can be used for short-term sedation to relieve anxiety or as a pre-operative medication. In some specialized cases, it is used off-label to treat neonatal jaundice or symptoms of alcohol withdrawal. Because of its potency and long-lasting effects, it is usually reserved for cases where other medications have not been effective.
The most common side effects of Phenobarbital include significant drowsiness, dizziness, and a feeling of being 'hungover' or sluggish. Patients often experience ataxia, which is a lack of coordination or unsteadiness while walking. In children and the elderly, it can sometimes cause paradoxical excitement, leading to irritability or hyperactivity instead of sedation. Other frequent issues include nausea, vomiting, and a dull headache. Because the drug stays in the body for a long time, these effects may persist throughout the day even if the dose is taken at night.
No, you must strictly avoid alcohol while taking Phenobarbital. Both substances are central nervous system depressants, and taking them together creates a dangerous 'additive effect.' This means the combination can slow your breathing and heart rate to life-threatening levels much more quickly than either substance alone. Even small amounts of alcohol can cause extreme drowsiness, loss of consciousness, or a fatal overdose. If you have a history of alcohol use, it is vital to discuss this with your doctor before starting treatment.
Phenobarbital is generally not considered safe during pregnancy and is classified as Category D, meaning there is evidence of risk to the human fetus. It has been linked to an increased risk of birth defects such as cleft lip, cleft palate, and heart abnormalities. Additionally, it can cause Vitamin K deficiency in the newborn, which increases the risk of dangerous bleeding. However, because uncontrolled seizures also pose a major risk to both the mother and the baby, a doctor may decide that Phenobarbital is necessary. In such cases, high-dose folic acid and Vitamin K supplementation are typically required.
The time it takes for Phenobarbital to work depends on the formulation and the condition being treated. When taken orally for seizure prevention, it may take several hours to reach peak levels in the blood, and it can take several weeks of consistent dosing to reach a 'steady state' where the drug is most effective. For emergency use, such as status epilepticus, the injectable form begins working within 5 minutes, though its full effect on the brain may take up to 30 minutes. Patients should not expect immediate relief from chronic seizure disorders after just one oral dose.
You should never stop taking Phenobarbital suddenly, as doing so can be extremely dangerous. Abrupt discontinuation can trigger 'rebound' seizures or status epilepticus, which are continuous seizures that do not stop and require emergency medical intervention. Furthermore, because the body becomes physically dependent on the drug over time, sudden withdrawal can cause severe symptoms like tremors, hallucinations, high fever, and delirium. If the medication needs to be stopped, your healthcare provider will create a gradual tapering schedule to slowly lower the dose over several weeks or even months.
If you miss a dose of Phenobarbital, take it as soon as you remember. However, if it is almost time for your next scheduled dose (within a few hours), you should skip the missed dose and simply take your next dose at the regular time. Do not take two doses at once to make up for the missed one, as this can lead to toxicity due to the drug's very long half-life. Maintaining a consistent schedule is key to preventing breakthrough seizures. If you miss more than one dose, contact your healthcare provider for specific instructions.
Weight gain is not typically considered a primary or common side effect of Phenobarbital, unlike some other anticonvulsants like valproic acid. However, because Phenobarbital causes significant sedation and lethargy, some patients may become less physically active, which can indirectly lead to weight gain over time. Some patients also report changes in appetite. If you notice significant or rapid changes in your weight while taking this medication, you should discuss them with your doctor to rule out other causes or metabolic changes.
Phenobarbital has an exceptionally high number of drug interactions because it speeds up the liver's ability to process other medications. It can make birth control pills, blood thinners like warfarin, and many other drugs much less effective. It also has dangerous interactions with other sedatives, including benzodiazepines and opioid pain medications. Because of these complexities, you must provide your doctor and pharmacist with a complete list of every medication, supplement, and herb you are taking. No new medications should be started without checking for an interaction with Phenobarbital.
Yes, Phenobarbital is available as a generic medication and is generally very inexpensive. It is sold under its generic name, although in the past, it was well known by the brand name Luminal. Generic versions are available in various tablet strengths and as an oral elixir. Because the therapeutic range is narrow, it is often recommended to stay with the same manufacturer of the generic drug once a stable blood level has been reached. If your pharmacy changes your generic manufacturer, your doctor may want to re-check your blood levels.