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How long does phenobarbital stay in your system?

Its effects wear off after 12 hours, but it sticks around in your body for several days to weeks
Heidi Borst
By | May 5, 2025 Medically reviewed by Peter Lourgos, MD, JD
Clock next to medication - How long does phenobarbital stay in your system?

Key takeaways

  • Phenobarbital can stay in your system for several days to weeks.

  • Body mass, overall health, and dosage influence phenobarbital’s duration in the system.

  • A healthcare professional should manage detoxification to ensure safety and effectiveness.

In this article:

Phenobarbital belongs to a drug class called barbiturates, which are primarily used as seizure medications. Barbiturates are sedative-hypnotic medications, meaning they help you feel sleepy and relaxed. Phenobarbital is FDA approved to prevent and treat several types of seizure disorders, including epilepsy and status epilepticus. The anti-epileptic is also used in addiction treatment for the management of withdrawal symptoms associated with benzodiazepine and alcohol dependence. Although phenobarbital was once widely prescribed for anxiety and insomnia, its use for these conditions has been largely replaced with safer medications.

The way phenobarbital works is pretty interesting: It increases levels of a brain chemical called gamma-aminobutyric acid (GABA), which slows down brain activity. These calming and sedative effects stop seizures, reduce anxiety, and lead to somnolence.

Phenobarbital is a long-acting barbiturate—its effect lasts up to 12 hours, and it can stay in your system for several days to weeks, depending on factors like dosage and individual metabolism.

How long does phenobarbital stay in your system?

The half-life of phenobarbital is quite long, lasting anywhere from two to seven and a half days, with an average of about five days. For adults, it can take between 53 and 118 hours for half of the drug to leave the body, while for kids and newborns, it can range from 60 to 180 hours. This means it stays in the system for quite a while!

According to Anoop Singh, MD, a board-certified psychiatrist with Mindpath Health, the time of onset, peak concentration, and duration of action for phenobarbital depend on the dose, route of administration (oral, intramuscular, or slow intravenous infusion), other medications a patient may be taking, and their medical status. 

  • Oral administration: When taken by mouth, it takes 30 to 60 minutes to start working. The highest levels in the blood show up in 8 to 12 hours, and it reaches the brain in about 10 to 15 hours.
  • Intravenous (IV) administration: This method is used in emergencies for severe seizures. It works very fast, usually in less than five minutes, with the strongest effects happening around 15 minutes after injection. However, it’s given slowly, so the peak effect is felt in about four to six hours.
  • Intramuscular administration: This method is less common and takes longer to work than IV.

Phenobarbital can be detected via urine, blood, saliva, and hair tests, says Charles Sweet, MD, MPH, a board-certified psychiatrist and medical adviser for Linear Health. “Urine tests are most commonly used in drug screenings, and hair tests are useful for detecting long-term use. Blood tests are often used to monitor the concentration of the drug and ensure safe and effective dosing,” he says. 

  • Blood tests are the most accurate and are often used to check phenobarbital levels up to seven days after use. They help providers ensure the drug is at the right level, ideally between 10 and 40 micrograms/mL, explains Dr. Singh. He says levels below this may mean the dose is too low, while levels above 40 to 50 micrograms/mL can be risky. Anything over 80 micrograms/mL could be dangerous.
  • Urine tests are commonly used for drug screening, especially in substance use monitoring and hospital settings. They’re easier to perform and can detect phenobarbital for up to 15 days after use.
  • Saliva tests are great for detecting recent use (up to two days).
  • Hair tests can show drug use over a longer period (up to 90 days).

Factors that influence how long phenobarbital stays in your system

Several factors can impact how long phenobarbital stays in your system, according to Dr. Singh. They include:

1. Body mass

“Phenobarbital is lipophilic (fat-soluble), meaning it can be stored in adipose tissue,” says Dr. Singh. Individuals with higher body fat percentages may experience slower drug clearance as the drug is gradually released back into circulation, resulting in prolongation of its effects, he explains. Maintaining a healthy weight through balanced nutrition and regular exercise can help circumvent this effect. 

2. Overall health

Phenobarbital is mainly processed by liver enzymes, so a patient’s liver function is particularly critical, says Dr. Singh. If someone has liver issues from conditions like cirrhosis, hepatitis, or fatty liver disease, it can slow down how quickly the body breaks down the drug. 

About 25% to 50% of phenobarbital is removed from the body through the urine, so if kidney function is impaired, it can lead to a buildup of the drug. Additionally, older individuals and those with slower metabolic rates may take longer to clear the medication.

Because of these factors, people with liver or kidney problems and older adults should be closely monitored by their healthcare provider, who may need to adjust their doses accordingly.

3. Dose

“High doses increase the amount that needs to be processed and eliminated, so it will generally stay in the body for a longer period of time,” says Dr. Sweet. When prescribed, following the recommended dosage is essential to minimize potential risks and communicate openly with your healthcare provider.

4. Frequency of administration

Dr. Sweet explains that regular phenobarbital use causes the drug to build up in a patient’s system, extending the drug’s presence in the body, even if they stop taking it—which should never be done without talking to their provider. To avoid complications from frequent use, patients should consult a medical professional regarding the best administration schedule. 

Side effects and risks of phenobarbital

According to Dr. Singh, phenobarbital, which is a powerful central nervous system (CNS) suppressant, comes with the following potential side effects, risks, and contraindications:

  • Side effects: Phenobarbital can cause sleepiness, breathing issues, and dangerously low blood pressure or heart rate. Long-term use may affect cognitive function and increase psychiatric risks like depression and anxiety, particularly in those who misuse it.
  • Risks: As a Schedule IV controlled substance, phenobarbital carries the potential for addiction, tolerance, and severe withdrawal symptoms. While daily use can be beneficial for some individuals, it must be managed carefully due to potential side effects and the risk of dependence. While it can be life-saving for certain serious conditions, improper use can lead to dangerous outcomes, including serious injury or death.
  • Drug interactions: Phenobarbital can interact with central nervous system depressants, pain medications, and other drugs. It can also seriously affect levels of Seroquel (quetiapine) in the blood—an antipsychotic medication used to treat bipolar disorder and schizophrenia. Consult your healthcare provider about all medications, dietary supplements, and substances being used to avoid dangerous interactions.
  • Health conditions: Health issues like liver disease or kidney disease, respiratory problems, and mental health conditions require careful evaluation before using phenobarbital. It’s also advised that individuals over 65 and those who are pregnant, trying to conceive, or breastfeeding avoid this medication. 

How long does it take for side effects to go away after stopping phenobarbital?

Phenobarbital can stay in the body for a very long time due to the long half-life, emphasizes Dr. Singh. While the dose-dependent side effects may improve after the effects of the medication wear off, certain side effects, especially those related to prolonged or improper use, can last for a long time or even be permanent. These can include cognitive impairment, mood and behavioral disturbances, dependence, and withdrawal, and in some cases, respiratory problems and liver damage.

Detox and withdrawal management

Phenobarbital is primarily metabolized by the liver and excreted by the kidneys, with its half-life affecting the duration of its presence in the system. Individuals taking phenobarbital or other barbiturates, such as secobarbital, pentobarbital, and amobarbital, should not stop taking them without consulting their healthcare provider, Dr. Singh urges. That’s because sudden discontinuation can result in the onset of acute and potentially life-threatening withdrawal symptoms, including:

  • Anxiety
  • Muscle twitching
  • Uncontrollable shaking of a part of the body
  • Weakness
  • Dizziness
  • Changes in vision
  • Nausea
  • Vomiting
  • Seizures
  • Confusion
  • Difficulty falling asleep or staying asleep
  • Dizziness or fainting when getting up from a lying position

There is no established medical timeline for phenobarbital withdrawal, says Dr. Singh, and withdrawal symptoms may last a few days or a few weeks, depending on the dose and duration for which an individual has been taking it. Most individuals with a relatively low risk of withdrawal can reduce the medication dose over a two-week period. Those at high risk will probably need a gradual or prolonged detox. For some individuals, additional medication(s) may be used during the detox process.

The following tips can help manage the withdrawal effects of phenobarbital:

  • Gradual tapering: Slowly reducing the dose can help minimize withdrawal effects.
  • Support system:  Engaging with support groups or counseling can aid emotional and psychological management.
  • Adequate nutrition: Staying hydrated and maintaining a balanced diet can support overall health during withdrawal.

Phenobarbital alternatives

If phenobarbital isn’t right for you, there are several alternatives that may be considered, including:

Discuss alternative options with a healthcare provider, who can help weigh the pros and cons of each and the potential withdrawal effects of discontinuing phenobarbital.