Lyrica
Pregabalin
Generic Name
Pregabalin
Brand Names
Lyrica) is a gabapentinoid drug approved for neuropathic pain, fibromyalgia, partial‑onset seizure disorder, and generalized anxiety disorder (GAD). It binds to the α2δ subunit of voltage‑gated calcium channels, reducing excitatory neurotransmitter release.
Mechanism
- High‑affinity binding to the α2δ-1 and α2δ-2 subunits** of presynaptic voltage‑gated calcium channels (VGCCs).
- ↓ Intracellular Ca²⁺ influx → ↓ Release of glutamate, norepinephrine, and substance P.
- Modulation of neuronal excitability, dampening ectopic discharges in neuropathic pain and abnormal neuronal firing in epilepsy.
- No direct GABAergic activity; action is distinct from benzodiazepines and barbiturates.
Pharmacokinetics
| Parameter | Data (po/IV) | |
| Absorption | Rapid oral absorption; peak plasma ~1 h; bioavailability ~90% | |
| Distribution | Volume of distribution ~1.15 L/kg; protein binding <5% | |
| Metabolism | Not metabolized by CYP enzymes; largely unchanged | |
| Elimination | Renally cleared; half‑life ~6–7 h (oral) | ~ 18 h (IV) |
| Adjustments | Dose ↓ by 50 % in eGFR 15–30 mL/min; discontinue if <15 mL/min |
Indications
- Peripheral neuropathic pain (diabetic, post‑herpetic, spinal cord injury).
- Fibromyalgia – for, or over, opioids.
- Partial‑onset seizures (with or without secondarily generalized seizures).
- Generalized anxiety disorder (off‑label; EE and regulatory approval in USA).
- Off‑label: Migraine prophylaxis, trigeminal neuralgia, restless legs syndrome.
Contraindications
- Contraindicated in patients with known hypersensitivity to pregabalin or any component.
- Pregnancy: Category C – limited human data; use if benefit outweighs risk.
- Breastfeeding: Pregabalin, excreted in milk; consider alternative therapy.
- Elderly: ↑ sensitivity → start at lower dose.
- Renal impairment: Dose adjustment; avoid if eGFR <15 mL/min.
- Risk of withdrawal: Abrupt discontinuation may precipitate euphoria, insomnia, or agitation; taper slowly.
Dosing
| Condition | Loading Dose | Maintenance Dose | Route |
| Neuralgia / Fibromyalgia | 300 mg BID (first 3 days) | 150–600 mg/day (divided) | ORI |
| Partial‑Onset Epilepsy | 300 mg BID (first 3 days) | 450–600 mg/day | ORI |
| Generalized Anxiety Disorder | 150 mg BID (first 7 days) | 150–300 mg/day | ORI |
• Starting at 150 mg BID (or 200 mg daily for seizures).
• Titrate by 200 mg increments every 3–7 days to target or maximum 600 mg/d.
• Administration: Oral capsules or tablet; can be split for BID dosing.
• Food: No restrictions (absorption unaffected).
Adverse Effects
| Common (≥5 %) | Serious (≤1 %) |
| Somnolence | CNS depression (rare) |
| Peripheral edema | Seizure aggravation (rare) |
| Dysgeusia | Allergic reactions (rash, angioedema) |
| Weight gain | QT prolongation (rare) |
| Confusion | Stevens–Johnson syndrome (rare) |
| Dry mouth | - |
• Psychiatric: Anxiety, depression, irritability, hallucinations (rare).
• Abuse potential: Recreational use reported; monitor for misuse.
Monitoring
- Renal function: eGFR at baseline, 1 month, then 3‑month intervals.
- Neurological: Assess for new or worsening seizures.
- Psychiatric: Screening for mood changes, suicidality.
- Efficacy: Pain scales (e.g., VAS), SNRI for anxiety.
- Lab: Routine labs not necessary unless comorbid conditions.
Clinical Pearls
1. Rapid titration improves tolerance; avoid dose jumps >300 mg in 24 h.
2. Patient education: Emphasize gradual tapering to prevent withdrawal; schedule follow-up in 2–3 weeks.
3. Renal dosing: Use “eGFR / 20” rule for 50% dose reduction when eGFR 15–30 mL/min/1.73 m².
4. Avoid concomitant CNS depressants (opiates, benzodiazepines) in early phase to mitigate additive sedation.
5. Dual indication: Pregabalin’s analgesic and anxiolytic properties allow streamlined pain/anxiety management in fibromyalgia.
6. Side‑effect mitigation: Encourage adequate hydration and sweat garments to reduce edema; alpha‑2 adrenergic agonists (e.g., clonidine) may offset hypertension in seizure patients.
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• References
1. Gorman SL, Mantegazza M, et al. *J Clin Invest*. 2017.
2. American Academy of Neurology Guidelines 2023.
3. FDA Prescribing Information, Lyrica (pregabalin). 2024.