Understanding Keppra (Levetiracetam)
Keppra, the brand name for levetiracetam, is a prescription medication used to control seizures in people with epilepsy. It is often prescribed alone or as an add-on treatment. Compared to many older antiepileptic drugs (AEDs), levetiracetam has a relatively clean pharmacokinetic profile, meaning it does not significantly interfere with the liver enzymes that metabolize many other medications. This is a major advantage, but it does not mean the drug is free from important interactions. Some interactions are due to additive side effects, while others involve altered drug levels or specific reactions.
Key drug interactions to avoid or manage
Central Nervous System (CNS) Depressants
Combining Keppra with other medications that cause drowsiness or sedation can result in dangerous additive effects, including increased sleepiness, confusion, and impaired coordination. This can significantly impact daily activities, such as driving or operating machinery.
Common CNS depressants to use with caution or avoid include:
- Benzodiazepines: These are used for anxiety and insomnia. Examples include alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan).
- Opioids: These are powerful pain-relieving medications, such as methadone, oxycodone, and codeine.
- Sedating Antihistamines: Certain allergy medications like diphenhydramine (Benadryl) can cause significant drowsiness.
- Alcohol: Alcohol consumption should be avoided while taking Keppra, as it can significantly enhance the sedative effects and potentially lower the seizure threshold.
Methotrexate
A potentially serious interaction exists between Keppra and the chemotherapy and immunosuppressive drug methotrexate. While the exact mechanism is not fully understood, co-administration can increase the concentration of methotrexate in the blood, leading to a heightened risk of methotrexate toxicity. The consequences can include severe side effects, such as acute kidney failure, and can be fatal.
Management of this interaction requires:
- Careful monitoring of methotrexate and Keppra blood levels.
- Consideration of temporarily switching to an alternative antiepileptic drug during methotrexate treatment.
Other Antiepileptic Drugs (AEDs)
While Keppra is often used alongside other AEDs, some combinations can increase the risk of certain side effects. Interactions can vary, and healthcare providers must monitor patients closely.
- Valproic acid: While early research suggested no significant pharmacokinetic interaction, combining Keppra with valproic acid can lead to additive CNS effects like increased dizziness, drowsiness, and confusion.
- Carbamazepine: Taking Keppra with carbamazepine may increase the risk of carbamazepine side effects, such as vision changes, dizziness, and unsteadiness.
- Clobazam: The FDA has issued a warning regarding the rare but serious drug reaction DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) for both Keppra and clobazam.
Herbal Supplements and Other Products
There is limited data on Keppra's interactions with herbal supplements, but caution is advised. Some herbs, like St. John's Wort or Ginkgo, can interfere with medication effectiveness or alter the seizure threshold. While cannabis and CBD haven't been specifically shown to interact, their use can increase sleepiness, potentially worsening a side effect of Keppra.
Other Medications
Other drug classes can also have undesirable interactions with levetiracetam. These include some antidepressants and antipsychotics that can increase the risk of sleepiness, as well as general anesthesia medications.
Comparison of Keppra vs. Older AEDs
| Aspect | Keppra (Levetiracetam) | Older AEDs (e.g., Carbamazepine, Phenytoin) |
|---|---|---|
| Hepatic Metabolism | Minimal interaction; does not induce or inhibit cytochrome P450 enzymes. | Significant hepatic enzyme induction, leading to numerous drug-drug interactions. |
| CNS Depression | Can cause drowsiness, fatigue, and dizziness, especially when combined with other CNS depressants. | Can cause similar or more pronounced CNS effects, often limiting tolerability. |
| Monitoring | Less routine blood level monitoring required for Keppra itself, but attention to interactions is still needed. | Regular therapeutic drug monitoring is often necessary due to significant drug-drug interactions and variable metabolism. |
| Drug-Drug Interactions | Fewer interactions overall, but critical interactions exist with drugs like methotrexate and CNS depressants. | Higher potential for drug interactions, affecting the efficacy of many other medications. |
What to do if an interaction occurs
If you believe you are experiencing a drug interaction, it is vital to contact your healthcare provider immediately. Symptoms may include excessive drowsiness, mood changes, increased seizures, or signs of an allergic reaction like a rash. Your doctor may need to adjust your dosages, change your medications, or perform additional monitoring. Do not stop taking Keppra suddenly, as this could cause an increase in seizure frequency.
Safety Considerations Beyond Interactions
The FDA has issued warnings regarding the potential for serious skin and allergic reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). This rare but life-threatening reaction can occur within weeks of starting Keppra and may begin with a fever and rash, progressing to organ injury. Patients should also be monitored for behavioral and mood changes, including irritability, aggression, and suicidal thoughts, which can occur with Keppra and other AEDs.
Conclusion
Keppra is a valuable antiepileptic medication with a favorable interaction profile compared to older drugs. However, patients and healthcare providers must remain vigilant about potential drug interactions, particularly with CNS depressants like alcohol and benzodiazepines, and with methotrexate. Given the potential for serious adverse effects like methotrexate toxicity and the rare DRESS reaction, proactive communication and careful monitoring are essential. Always inform your doctor and pharmacist of all prescription, over-the-counter, and herbal supplements you are taking to ensure your safety. For authoritative prescribing information, consult the FDA's official drug safety communications.
