BLACK BOX WARNING
- serious respiratory depression when combined with CNS depressants
pregabalin
Brand: Lyrica, Lyrica CR
⚠ BBW Beers Criteria Prototype: gabapentin
Drug Class: antiepileptic / analgesic
Drug Family: antiepileptic
Subclass: GABA analogue
Organ Systems: cns
Mechanism of Action
Binds alpha-2-delta subunit of voltage-gated calcium channels (like gabapentin but with higher affinity and linear absorption), reducing release of excitatory neurotransmitters.
alpha-2-delta subunit of voltage-gated calcium channels
Indications
- focal-onset seizures (adjunct)
- diabetic peripheral neuropathy
- postherpetic neuralgia
- fibromyalgia
- spinal cord injury neuropathic pain
Contraindications
- hypersensitivity to pregabalin
Adverse Effects
Common
- dizziness
- somnolence
- dry mouth
- edema
- blurred vision
- weight gain
Serious
- angioedema
- respiratory depression (with CNS depressants)
- PR interval prolongation
- myopathy/rhabdomyolysis (rare)
Pharmacokinetics (ADME)
| Absorption | Linear absorption (~90% bioavailability) regardless of dose — advantage over gabapentin |
| Distribution | Not protein-bound; Vd ~0.5 L/kg |
| Metabolism | Negligible metabolism; excreted unchanged |
| Excretion | Entirely renal; dose adjustment required for CrCl <60 mL/min |
| Half-life | 6 hours |
| Onset | Hours to days |
| Peak | 1.5 hours |
| Duration | 8–12 hours |
| Protein Binding | 0% |
| Vd | ~0.5 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| opioids | additive CNS and respiratory depression | major |
| benzodiazepines | additive CNS depression | moderate |
| thiazolidinediones | additive peripheral edema and weight gain | moderate |
Nursing Considerations
- Adjust dose based on creatinine clearance; pregabalin is renally eliminated and must be reduced in proportion to CrCl
- Monitor for signs of angioedema (face, mouth, neck swelling) — discontinue immediately if suspected
- Pregabalin is a Schedule V controlled substance due to misuse potential — assess for substance use disorder history
- Taper over minimum 1 week when discontinuing to avoid withdrawal symptoms (insomnia, nausea, headache, diarrhea)
Clinical Pearls
- Unlike gabapentin, pregabalin has linear pharmacokinetics (predictable bioavailability across doses), making titration more predictable
- FDA-approved for fibromyalgia — one of only three drugs approved for this indication (along with duloxetine and milnacipran)
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.