Is it safe to take Lyrica (pregabalin) and Neurontin (gabapentin) together?

Concurrent Use of Pregabalin (Lyrica) and Gabapentin (Neurontin)

Concurrent use of pregabalin (Lyrica) and gabapentin (Neurontin) is not recommended due to increased risk of adverse effects without additional therapeutic benefit. 1

Mechanism of Action and Therapeutic Duplication

• Both pregabalin and gabapentin are α2δ ligands that work through similar mechanisms, binding to the α2δ-1 subunit of voltage-gated calcium channels 2
• Both medications are approved for similar neuropathic pain conditions, making concurrent use therapeutically redundant 1
• Both drugs reduce neurotransmitter release in neuronal tissue through similar pathways, creating a therapeutic duplication when used together 2

Risks of Combined Therapy

• Combined use significantly increases the risk of adverse effects including:
  • Enhanced drowsiness, dizziness, and sedation 1
  • Increased risk of ataxia and cognitive impairment 1
  • Potential for respiratory depression, especially when combined with other CNS depressants 3
• The American Geriatrics Society identifies this combination as particularly problematic in older adults due to increased fall risk 3
• Concurrent use with opioids or benzodiazepines further increases risk of serious adverse effects 3

Appropriate Management Approach

• Choose either pregabalin OR gabapentin based on patient-specific factors: 1

  • For patients requiring more predictable dosing: Consider pregabalin due to its linear pharmacokinetics 4
  • For patients with cost concerns: Gabapentin may be more affordable 1
  • For patients with renal impairment: Both require dose adjustment, but pregabalin may be easier to dose 4

• When switching between medications: 1

  • Gradually taper the first medication while introducing the second
  • Allow for a transition period to minimize withdrawal symptoms
  • Monitor closely for adverse effects during the transition

Dosing Considerations for Individual Agents

• Pregabalin: 4

  • Starting dose: 50-75 mg twice daily
  • Effective dose range: 150-600 mg/day in divided doses
  • Titrate gradually over 1-2 weeks to minimize side effects

• Gabapentin: 4

  • Starting dose: 100-300 mg at bedtime or 100-300 mg three times daily
  • Effective dose range: 900-3600 mg/day in divided doses
  • Requires slower titration (3-8 weeks) plus 2 weeks at maximum dose for adequate trial

Alternative Approaches for Difficult-to-Treat Pain

• For patients with inadequate response to a single gabapentinoid at maximum tolerated dose: 1
  • Consider duloxetine (60-120 mg/day) for diabetic neuropathic pain 3
  • Consider tricyclic antidepressants (with caution in older adults) 3
  • Alpha lipoic acid may be beneficial for HIV-associated or diabetic peripheral neuropathy 3
  • Topical agents like lidocaine patch may provide relief with minimal systemic effects 3

Special Considerations

• In elderly patients, use lower starting doses and slower titration of either medication to minimize adverse effects 3, 4
• Never abruptly discontinue either medication; always taper gradually over at least 1 week to avoid withdrawal symptoms 4
• For patients with renal impairment, dose adjustment is required for both medications 4

Remember that while some research has explored potential benefits of combination therapy 5, current clinical guidelines and evidence strongly favor using either pregabalin or gabapentin alone rather than in combination 1.