For many individuals living with epilepsy, managing a medication schedule that requires multiple daily doses can be challenging. Forgetting doses is a common problem, which can lead to breakthrough seizures and a loss of seizure control. To address this, pharmaceutical companies have developed extended-release (XR) formulations of existing medications and novel drugs with naturally long half-lives that allow for once-daily dosing. These single-dose regimens can offer greater convenience, improve adherence, and ultimately lead to better health outcomes for patients with epilepsy.
The Benefits of a Once-Daily Regimen
Switching to a once-daily antiseizure medication (ASM) can significantly impact a person's life by simplifying their treatment schedule. The primary benefits include:
- Improved Adherence: Taking a medication once per day is easier to remember than taking it multiple times. This leads to higher rates of treatment adherence, which is vital for maintaining a stable therapeutic level of the drug in the body and preventing seizures.
- Greater Convenience: A single daily dose can make treatment less disruptive to a person's daily routine, including work, school, and social activities. This is especially helpful for children and adolescents who may be reliant on caregivers for medication.
- Stable Drug Levels: Extended-release formulations are designed to release the medication slowly and consistently throughout the day. This reduces the peaks and troughs in drug concentration, which can help minimize side effects and improve seizure control.
Common Once-Daily Antiseizure Medications
Several effective ASMs are available in once-daily formulations, either as extended-release versions of standard drugs or as inherently long-acting agents. The suitability of each depends on the type of seizure and individual patient factors.
Levetiracetam Extended-Release (Keppra XR)
- Uses: Approved for partial-onset seizures in patients aged 12 and older. It can be used alone (monotherapy) or with other ASMs.
- Mechanism: Thought to work by inhibiting nerve cell chemicals in the brain to reduce electrical activity.
- Dosing: Started at a low dose and gradually increased over several weeks under a doctor's supervision.
Oxcarbazepine Extended-Release (Oxtellar XR)
- Uses: The extended-release version (Oxtellar XR) is indicated for partial-onset seizures in adults and children 6 years and older, used as either monotherapy or adjunctive therapy.
- Mechanism: Believed to work by blocking sodium channels in the brain, preventing the spread of abnormal electrical signals.
- Dosing: Taken once daily on an empty stomach.
Topiramate Extended-Release (Qudexy XR, Trokendi XR)
- Uses: These once-daily extended-release formulations are used for partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome.
- Mechanism: Works in several ways, including blocking sodium channels and enhancing the activity of the inhibitory neurotransmitter GABA.
- Dosing: Initial dosing is started slowly and titrated up to the therapeutic range.
Perampanel (Fycompa)
- Uses: Approved for partial-onset seizures (ages 4 and up) and adjunctive treatment for primary generalized tonic-clonic seizures (ages 12 and up). It has a long half-life that makes once-daily dosing possible.
- Mechanism: Works as a selective non-competitive antagonist of the AMPA glutamate receptor, reducing neuronal excitability.
- Dosing: Titrated gradually, with the maximum dose dependent on factors like seizure type and concomitant medications.
Cenobamate (Xcopri)
- Uses: A newer once-daily option for the treatment of partial-onset seizures in adults. Its efficacy has been observed relatively quickly in clinical trials.
- Dosing: As with many ASMs, it is initiated at a low dose and increased slowly to reduce the risk of adverse effects.
Zonisamide (Zonegran)
- Uses: Approved for the adjunctive treatment of partial-onset seizures in adults.
- Dosing: Often taken once daily due to its long half-life, though twice-daily dosing may be used. Like other ASMs, it requires slow titration.
Comparison of Once-Daily Seizure Medications
| Medication (Brand Name) | Approved Seizure Types | Key Side Effects | Special Considerations |
|---|---|---|---|
| Levetiracetam XR (Keppra XR) | Partial-onset (≥12 yrs) | Sleepiness, dizziness, irritability | Generally fewer drug interactions than other ASMs |
| Oxcarbazepine XR (Oxtellar XR) | Partial-onset (≥6 yrs) | Dizziness, drowsiness, nausea, low sodium levels | Take on an empty stomach; can interact with oral contraceptives |
| Topiramate XR (Qudexy XR, Trokendi XR) | Partial-onset, generalized tonic-clonic, LGS | Weight loss, fatigue, cognitive issues, tingling | Risk of kidney stones, requires proper hydration |
| Perampanel (Fycompa) | Partial-onset (≥4 yrs), GTC (≥12 yrs) | Dizziness, somnolence, irritability, aggression | Behavior and psychiatric adverse events can occur |
| Cenobamate (Xcopri) | Partial-onset (adults) | Dizziness, fatigue, double vision | Effective for treating uncontrolled focal seizures |
| Zonisamide (Zonegran) | Partial-onset (adjunctive) | Drowsiness, fatigue, cognitive effects, rash | Slow titration is necessary; monitor for serious rash |
Considerations for Once-Daily Dosing
While the convenience of a once-daily regimen is undeniable, there are important factors to consider:
- Missed Doses: If a single dose is missed, the drop in drug level in the body can be greater and more significant than missing one of several smaller doses. This can increase the risk of a breakthrough seizure. Patients must be diligent about taking their medication consistently.
- Formulation and Bioavailability: Extended-release formulations of the same drug may have different bioavailability profiles. Switching from an immediate-release version to an XR version requires careful monitoring and potential dose adjustments. Patients should be aware of the specific brand and generic versions they are taking.
- Side Effects: Some side effects, like dizziness or sedation, may be more pronounced during the initial titration phase. Doctors will work with patients to find the optimal dose that controls seizures while minimizing adverse effects.
- Interactions: Some ASMs have important interactions with other medications, including hormonal contraceptives. A doctor should always be informed of all drugs being taken.
Conclusion
For many patients with epilepsy, once-daily seizure medications represent a significant improvement in treatment management, offering enhanced convenience and potentially better adherence. The development of extended-release formulations and novel long-acting drugs has expanded the options available for single-dose therapy. Medications like Keppra XR, Oxtellar XR, Qudexy XR/Trokendi XR, Fycompa, Xcopri, and Zonisamide offer effective seizure control for a variety of seizure types. However, the choice of medication, proper dosing, and adherence strategies should always be determined in close consultation with a qualified healthcare provider. Patients should never stop or change their medication abruptly, as this can trigger severe seizures.
For more information on epilepsy and its management, visit the Epilepsy Foundation website.
