Can Flexeril (cyclobenzaprine) be taken with Keppra (levetiracetam) and Lamotrigine for seizure control and muscle spasms?

Safety of Taking Flexeril with Keppra and Lamotrigine

Flexeril (cyclobenzaprine) can generally be taken safely with Keppra (levetiracetam) and lamotrigine for patients requiring both seizure control and muscle spasm relief, as there are no significant pharmacokinetic interactions between these medications that would impact morbidity or mortality.

Medication Interactions Analysis

Levetiracetam (Keppra) and Cyclobenzaprine

• Levetiracetam has minimal drug interactions due to its unique pharmacokinetic profile:
  • It is primarily excreted unchanged through the kidneys (66% of administered dose) 1
  • It does not undergo significant hepatic metabolism via cytochrome P450 enzymes 1
  • It has minimal protein binding and does not induce or inhibit liver enzymes 1, 2

Lamotrigine and Cyclobenzaprine

• Lamotrigine is not classified as an enzyme-inducing antiepileptic drug (EIAED) 3
• Unlike older antiepileptic medications (phenytoin, phenobarbital, carbamazepine), lamotrigine does not significantly affect the cytochrome P450 system 2

Cyclobenzaprine Considerations

• Cyclobenzaprine is a muscle relaxant effective for acute skeletal muscle spasm 4
• The most common side effect is sedation, which is dose-dependent (more common at 10mg TID than 5mg TID) 4

Evidence-Based Recommendations

1. Dosing Considerations:

   • Start with lower doses of cyclobenzaprine (5mg TID rather than 10mg TID) to minimize sedation 4
   • Maintain regular dosing of levetiracetam and lamotrigine for seizure control

2. Monitoring Parameters:

   • Watch for excessive sedation or drowsiness, especially during the first 4 weeks of treatment 1
   • Monitor for any changes in seizure frequency or severity
   • Be alert for any signs of cognitive impairment or balance issues

3. Driving Safety:

   • Patients on chronic levetiracetam and lamotrigine therapy generally do not experience clinically meaningful driving impairment 3
   • However, adding cyclobenzaprine may temporarily increase sedation, so caution with driving is warranted initially

Potential Side Effects to Monitor

• Combined CNS depression: All three medications can cause some degree of sedation, so the additive effect should be monitored
• Cognitive effects: Monitor for any worsening of concentration, memory, or alertness
• Balance/coordination: Watch for increased risk of falls, especially in elderly patients

Common Pitfalls to Avoid

1. Avoid abrupt discontinuation of any of these medications, particularly the antiseizure medications, as this could precipitate seizures

2. Avoid other CNS depressants when possible (alcohol, benzodiazepines, opioids) as these could potentiate sedative effects

3. Don't substitute other muscle relaxants without considering their interaction profiles:

   • Some muscle relaxants may have stronger interactions with antiepileptic medications

4. Avoid enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) if possible, as these have more significant drug interactions than levetiracetam and lamotrigine 3, 2

Special Considerations

For patients with renal impairment, dose adjustment of levetiracetam may be necessary as it is primarily excreted by the kidneys 1.

For women of childbearing potential, levetiracetam may be preferred over valproate due to lower teratogenicity risk, though seizure control may be somewhat less effective 5, 6.

In conclusion, while all CNS-active medications carry some risk of additive sedation, the combination of cyclobenzaprine, levetiracetam, and lamotrigine does not present significant pharmacokinetic interactions that would contraindicate their concurrent use.