Can you take Phenergan with Keppra? Understanding the Risks

October 12, 2025 •

3 min read

According to the drug interaction checker on Drugs.com, using promethazine (Phenergan) together with levetiracetam (Keppra) may significantly increase side effects such as drowsiness and confusion. For this reason, it is critical to consult a healthcare provider to understand the full implications and potential risks associated with taking Phenergan with Keppra.

Quick Summary

Combining the antiepileptic Keppra with the antihistamine Phenergan can cause increased central nervous system depression, leading to heightened sedation, dizziness, and impaired coordination. This potentiation of side effects, including the potential to lower the seizure threshold, necessitates strict medical supervision.

Key Points

Additive CNS Depression: Combining Phenergan and Keppra can cause significantly heightened drowsiness, dizziness, and confusion due to their individual CNS depressant effects.
Impaired Motor Skills: The severe sedation can impair judgment, thinking, and motor coordination, increasing the risk for accidents.
Lowered Seizure Threshold: Phenergan has the potential to lower the seizure threshold, counteracting Keppra's therapeutic effects and increasing seizure risk for epileptic patients.
Need for Medical Supervision: Combining these medications should only be done under a doctor's strict guidance, and in many cases, it may be avoided entirely.
Non-Sedating Alternatives: Safer alternatives exist for allergy or nausea treatment, such as second-generation antihistamines, which avoid the CNS depressant risks.
Monitoring is Crucial: Any patient taking this combination must be closely monitored for excessive sedation or loss of seizure control.

A Closer Look at Promethazine and Levetiracetam

Keppra (levetiracetam) is an antiepileptic drug (AED) used to manage seizures, which can cause central nervous system (CNS) depression, including drowsiness and dizziness. Phenergan (promethazine), a first-generation antihistamine, is used for allergies, motion sickness, and as a sedative or anti-nausea medication. It also acts as a CNS depressant and causes significant sedation.

The Additive and Synergistic Dangers of Combined Use

Combining Keppra and Phenergan, both CNS depressants, can lead to additive or synergistic effects, meaning the combined impact on the CNS is greater than the sum of their individual effects. This interaction can result in severe drowsiness, confusion, and poor motor coordination.

Commonly Observed Symptoms of the Interaction:

Excessive Sedation: Increased sleepiness.
Dizziness and Confusion: Worsened dizziness and mental fog.
Impaired Motor Skills: Difficulty with coordination and concentration.
Exacerbated Behavioral Changes: Potentially restlessness or agitation.

Special Considerations for Epilepsy Patients

For individuals with epilepsy taking Keppra, combining it with Phenergan is particularly risky because Phenergan can lower the seizure threshold, increasing the chance of a seizure. This effect counteracts Keppra's purpose. Therefore, using promethazine in patients with a history of seizures requires extreme caution and strict medical supervision.

Comparison of Medications and Their Combined Effects


Feature	Keppra (Levetiracetam)	Phenergan (Promethazine)	Combined Effects	Medical Recommendation
Drug Class	Antiepileptic Drug (AED)	First-Generation Antihistamine, Sedative	Additive CNS Depression	Avoid or Use with Caution and Physician Guidance
Primary Function	Seizure prevention	Allergy, nausea, sedation	Heightened CNS effects and potential for lowered seizure threshold	Seek non-sedating alternatives or dose adjustments
CNS Effects	Common drowsiness, dizziness, fatigue, irritability.	Significant drowsiness, sedation, impaired mental alertness.	Substantial increase in drowsiness, confusion, dizziness, and impairment.	Monitor closely and avoid hazardous activities.
Seizure Risk	Reduces seizure activity.	Can potentially lower the seizure threshold.	Counteracts Keppra's effect, increasing seizure risk.	Close monitoring and physician consultation are vital.
Other Concerns	Potential for mood and behavioral changes.	Risk of anticholinergic effects and QTc prolongation (rare).	Increased anticholinergic activity and potential for arrhythmias.	Report any unusual symptoms, especially heart palpitations.

Managing the Risk: Alternatives and Precautions

Due to the significant risk of increased CNS depression and other complications, patients on Keppra should be extremely cautious about using Phenergan. Non-sedating alternatives for allergy or nausea relief, such as second-generation antihistamines like cetirizine (Zyrtec) or loratadine (Claritin), are generally safer for individuals with epilepsy.

If Phenergan use is deemed necessary by a healthcare provider, precautions include:

Dosage Adjustment: A doctor may adjust the dosage of either medication.
Close Monitoring: Monitoring for excessive sedation, confusion, or changes in seizure control is essential.
Avoid Hazardous Activities: Patients should avoid driving or operating machinery until they understand the effects of the combination.

Conclusion: Prioritizing Medical Expertise

While the drugs don't significantly affect each other's concentration in the body, their combined CNS depressant effects are a major concern. Given the risks of severe sedation and a potentially lowered seizure threshold, it is crucial to consult a healthcare professional before combining Phenergan and Keppra. Any decision to use them together requires a careful evaluation of risks versus benefits. Patients on epilepsy medication should always inform their doctor about all other medications, including over-the-counter and herbal products. For more information on promethazine safety, the National Institutes of Health provides detailed data.

Frequently Asked Questions

If you accidentally combine Phenergan and Keppra, you may experience extreme drowsiness, dizziness, and confusion. It is crucial to inform your doctor immediately and avoid activities that require mental alertness, like driving, until you know how the medications affect you.

For allergies, non-sedating, second-generation antihistamines like loratadine (Claritin) or cetirizine (Zyrtec) are generally safer alternatives. Your doctor can recommend the most appropriate option for your specific needs.

Yes, Phenergan (promethazine) has the potential to lower the seizure threshold, which means it can increase the risk of seizures, even at therapeutic doses. This is a significant concern for individuals with epilepsy.

If you must take both medications under a doctor's supervision, managing drowsiness involves starting with the lowest effective doses, potentially adjusting timing, and closely monitoring your symptoms. A non-sedating alternative is the safest and most effective strategy.

The interaction is particularly dangerous for patients with seizure disorders and the elderly, who are more susceptible to the CNS depressant and seizure-lowering effects. However, it poses a risk to anyone taking the combination by impairing motor and cognitive functions.

Phenergan causes significant sedation, drowsiness, and impaired mental performance. Keppra also commonly causes drowsiness, fatigue, and dizziness, especially during the first few weeks of treatment. The combination enhances these effects.

Yes, promethazine also has anticholinergic effects, which can be increased when combined with levetiracetam. There is also a rare risk of cardiac arrhythmias (QT prolongation) associated with combining these drugs.