Understanding Phenobarbital Side Effects

Phenobarbital is one of the oldest and most effective seizure medications still in use. Like all medications, it comes with potential side effects. The good news is that most side effects are mild and often improve as your body adjusts. However, some side effects are serious and require immediate medical attention.

This guide covers what to expect when you start Phenobarbital, which side effects are common, and which ones mean you should call your doctor right away.

New to Phenobarbital? Start with our overview: What Is Phenobarbital? Uses, Dosage, and What You Need to Know in 2026.

Common Side Effects of Phenobarbital

These side effects are relatively normal, especially when you first start taking Phenobarbital or after a dose increase. They usually improve within a few days to weeks:

• Drowsiness — This is the most common side effect. Phenobarbital works by calming brain activity, which can make you sleepy, especially at first.
• Dizziness — You may feel lightheaded or unsteady, particularly when standing up quickly.
• Headache — Mild headaches can occur as your body adjusts.
• Nausea or vomiting — Taking Phenobarbital with food can help reduce stomach upset.
• Excitement or hyperactivity — This is called a "paradoxical reaction" and is more common in children and older adults.

These side effects are usually manageable. If they persist for more than a couple of weeks or interfere with your daily life, talk to your doctor about adjusting your dose.

To understand why these effects happen, read: How Does Phenobarbital Work? Mechanism of Action Explained.

Serious Side Effects: When to Call Your Doctor

Contact your doctor as soon as possible if you experience any of the following:

• Severe drowsiness that does not improve — If you cannot stay awake during normal daily activities, your dose may be too high.
• Confusion or disorientation — Difficulty thinking clearly or not knowing where you are can indicate too much sedation.
• Depression or mood changes — Phenobarbital can affect mood. Report any new feelings of sadness, hopelessness, or emotional changes.
• Suicidal thoughts — All anticonvulsant medications carry a small increased risk of suicidal thoughts. If you or someone you know experiences these, seek help immediately. Call the 988 Suicide and Crisis Lifeline (call or text 988).

Emergency Side Effects: Call 911 Immediately

Go to the emergency room or call 911 if you experience:

• Difficulty breathing or slowed breathing — Phenobarbital can depress the respiratory system, especially at high doses or when combined with other sedating medications.
• Severe skin rash, blistering, or peeling — This could be a sign of Stevens-Johnson syndrome, a rare but life-threatening skin reaction.
• Swelling of the face, lips, tongue, or throat — This is a sign of angioedema, a serious allergic reaction.
• Fever with rash — This combination can indicate a serious drug reaction.

Side Effects in Special Populations

Children

Children may experience paradoxical excitement instead of drowsiness. They may become hyperactive, irritable, or have trouble sleeping. This is more common with Phenobarbital than with many other seizure medications.

Older Adults

Phenobarbital is generally not recommended for older adults according to the Beers Criteria. Older adults are more sensitive to its sedating effects, which increases the risk of falls, confusion, and cognitive impairment. If you are over 65 and take Phenobarbital, your doctor should monitor you closely.

Pregnant Women

Phenobarbital is classified as Pregnancy Category D, meaning it can cause harm to an unborn baby. However, uncontrolled seizures during pregnancy are also dangerous. Do not stop taking Phenobarbital without talking to your doctor first — the risks of stopping must be weighed against the risks of continuing.

Long-Term Side Effects

When taken for months or years, Phenobarbital can cause:

• Vitamin D deficiency and bone weakening — Phenobarbital increases the breakdown of vitamin D, which can lead to osteoporosis over time. Your doctor may recommend vitamin D supplements and periodic bone density scans.
• Cognitive effects — Some studies suggest long-term use may affect memory and concentration. Regular cognitive check-ups can help catch any changes early.
• Dependence — Phenobarbital is habit-forming. Your body can become physically dependent on it, which means stopping suddenly can cause serious withdrawal symptoms, including seizures.

Drug Interactions That Can Worsen Side Effects

Certain medications and substances can make Phenobarbital side effects worse or more dangerous:

• Alcohol — Never drink alcohol while taking Phenobarbital. The combination can cause life-threatening respiratory depression.
• Opioid pain medications — Combining opioids with Phenobarbital increases the risk of severe sedation and breathing problems.
• Benzodiazepines (like Valium or Xanax) — These add to the sedation and respiratory depression caused by Phenobarbital.
• Other sedating medications — Antihistamines, sleep aids, and muscle relaxants can all increase drowsiness.

For a complete list of interactions, read: Phenobarbital Drug Interactions: What to Avoid and What to Tell Your Doctor.

Tips for Managing Phenobarbital Side Effects

• Take it at bedtime — If drowsiness is your main issue, ask your doctor if you can take your full dose at night.
• Take it with food — This can reduce nausea and stomach upset.
• Stay hydrated — Drink plenty of water throughout the day.
• Avoid driving at first — Until you know how Phenobarbital affects you, do not drive or operate heavy machinery.
• Never stop suddenly — Tapering off Phenobarbital must be done under medical supervision to avoid withdrawal seizures.
• Keep a side effect diary — Track what you experience and when. This helps your doctor make informed decisions about your treatment.

When to Talk to Your Doctor About Switching Medications

If Phenobarbital side effects are significantly affecting your quality of life and do not improve with dose adjustments, it may be time to discuss alternatives. Several newer anticonvulsants may have fewer side effects for some patients. Learn more: Alternatives to Phenobarbital.

The Bottom Line

Most Phenobarbital side effects are mild and temporary. Drowsiness, dizziness, and nausea are the most common, and they usually get better with time. Serious side effects like breathing problems, severe skin reactions, or suicidal thoughts are rare but require immediate medical attention.

If you take Phenobarbital, stay in regular contact with your doctor, report any new or worsening symptoms, and never change your dose without medical guidance.

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