Can a patient take Pregabalin and Gabapentin (Neurontin) together?

Combining Pregabalin and Gabapentin: Not Recommended

Pregabalin and gabapentin should NOT be taken together as they are therapeutic duplicates with the same mechanism of action, and combining them significantly increases the risk of adverse effects without providing additional pain relief. 1, 2

Why These Medications Should Not Be Combined

Identical Mechanism of Action

• Both pregabalin and gabapentin bind to the same voltage-gated calcium channel at the α2δ subunit and inhibit neurotransmitter release through identical mechanisms 3
• Using both medications simultaneously represents therapeutic duplication—essentially taking two versions of the same drug 2
• The FDA drug label explicitly confirms that gabapentin coadministration does not alter pregabalin pharmacokinetics, indicating no synergistic benefit 1

Documented Adverse Effects from Combination Use

• A case report documented a patient prescribed both medications who developed drowsiness, dizziness, fatigue, and ataxia—all of which resolved when pregabalin was discontinued 2
• Both medications cause dose-dependent dizziness (23-46%), somnolence (15-25%), peripheral edema, and weight gain 3, 4
• Combining these agents amplifies these adverse effects without improving pain control 2

Evidence-Based Combination Therapy Alternatives

• Guidelines support combining gabapentinoids with OTHER drug classes (not with each other), such as: 5
  • Opioids (morphine, oxycodone) combined with gabapentin or pregabalin
  • Tricyclic antidepressants (nortriptyline) combined with gabapentin
  • Topical lidocaine combined with pregabalin
• The combination of nortriptyline and gabapentin was superior to either medication alone in randomized trials 5

Appropriate Clinical Approach

If Patient Is Currently on Gabapentin

• Transition to pregabalin if gabapentin is ineffective or poorly tolerated (not add pregabalin to gabapentin) 3
• Start pregabalin at 75 mg twice daily while continuing morning gabapentin dose for the first few days, then gradually taper gabapentin over several days to weeks 4
• Pregabalin offers faster pain relief (within 1.5-3.5 days vs. 2+ months for gabapentin) and more predictable dosing due to linear pharmacokinetics 3, 4

If Patient Is Currently on Pregabalin

• Optimize pregabalin dosing first before considering alternatives 4
• Standard effective dose is 300 mg/day (150 mg twice daily) with adequate trial of 4 weeks 4, 6
• Maximum dose of 600 mg/day should only be used if inadequate response at 300 mg/day and patient tolerates medication well 4

If Single Agent Fails

• Add a medication from a DIFFERENT drug class, not another gabapentinoid 5
• Consider tricyclic antidepressants, SNRIs, or opioids as combination therapy 5
• For neuropathic pain specifically, guidelines strongly recommend using neuropathic pain medications (gabapentin, carbamazepine, or pregabalin—choose ONE) with opioids 5

Critical Safety Considerations

Comparative Efficacy

• Head-to-head trial showed gabapentin was superior to pregabalin with fewer and less severe adverse events (GBP adverse events: 7 [19%] vs PGB: 31 [81%]; P = .002) 7
• Both medications significantly reduced pain, but gabapentin showed superior pain reduction (mean reduction GBP: 1.72 vs PGB: 0.94; P = .035) 7
• Guidelines suggest gabapentin as first-line with pregabalin considered only after inadequate response to gabapentin 3

Renal Dosing Requirements

• Both medications require mandatory dose reduction in renal impairment as they are eliminated unchanged by the kidneys 3, 4
• For pregabalin: reduce total daily dose by ~50% for CrCl 30-60 mL/min, 75% for CrCl 15-30 mL/min, and 85-90% for CrCl <15 mL/min 4

Abuse Potential Warning

• Both medications have documented misuse potential, particularly in individuals with history of recreational polydrug misuse who may self-administer dosages 3-20 times higher than clinically advisable 8
• Physicians should carefully evaluate previous history of drug abuse before prescribing 8

Bottom Line for This Patient

Contact the patient to explain that taking both medications together is not medically appropriate and increases risk of serious side effects including severe dizziness, drowsiness, and falls. 2 The prescriber should choose ONE gabapentinoid (preferably gabapentin based on superior tolerability) and optimize that single agent, or add a medication from a different drug class if additional pain control is needed. 3, 7