Generic Name

Pregabalin

Brand Names

Lyrica® among others.

Mechanism

• Binding target: *Pregabalin* selectively binds to the α2δ subunit of voltage‑gated calcium channels in the central nervous system.
• Resulting effect: This reduces calcium influx into neurons, lowering release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P.
• Outcome: Diminished neuronal hyperexcitability leads to analgesia and antiepileptic activity.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration within 1–1.5 h.
• Bioavailability: ~90 % and not affected by food.
• Distribution: ~31 % protein binding; crosses the blood–brain barrier efficiently.
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Elimination: Renal clearance is dose‑dependent; half‑life ~7 h (shorter in patients >75 kg).
• Special populations:
• *Renal impairment:* Dose adjustment required; CrCl ≤ 30 mL/min, reduce to 150 mg/day.
• *Hepatic disease:* No dose adjustment needed.

Indications

• Neuropathic pain (diabetic neuropathy, post‑herpetic neuralgia).
• Peripheral neuropathic pain associated with spinal cord injury and complex regional pain syndrome.
• Partial‑onset seizures as add‑on therapy.
• Generalized anxiety disorder (off‑label in many countries).
• Fibromyalgia (off‑label).

Contraindications

• Contraindications:
• Known hypersensitivity to pregabalin or excipients.
• Severe renal impairment (CrCl ≤ 30 mL/min).
• Warnings:
• Pregnancy: Category C; use only if benefits outweigh risks.
• Pediatric use: Under‑12 yrs → off‑label; under‑18 yrs → limited data.
• Elderly: ↑ risk of dizziness, sedation, falls.
• Breastfeeding: Minimal data; avoid unless benefits noted.
• Use caution in patients with cardiovascular disease, drug‑induced QT prolongation, and those on CNS depressants.

Dosing

• Titration: Increase by 150 mg/day every week until therapeutic effect or adverse effect manifests.
• Per‑rectal use: None available.

Adverse Effects

Common:
• Dizziness
• Somnolence
• Peripheral edema
• Weight gain (≈0.5–1 kg over 6 months)
• Blurred vision

Serious / Rare:
• Hypersensitivity reaction (rash, angioedema)
• Suicidal ideation or behavior
• Severe hyponatremia (rare)
• Visual disturbances (intraocular pressure increase)

Monitoring

• Renal function: CrCl before initiation, then every 4–6 months or if renal function changes.
• Neurological status: Assess for dizziness, somnolence, balance.
• Weight & fluid status: Monitor for edema and weight gain.
• Mental status: Screen for suicidal ideation, especially in patients with mood disorders.
• Efficacy: Pain scores (VAS/NRS), seizure frequency, anxiety rating scales.

Clinical Pearls

• No major CYP interactions: *Pregabalin* avoids many common drug‑drug interactions; ideal for polypharmacy patients.
• Taper gradually: Abrupt cessation can precipitate withdrawal seizures; reduce by ~35 % over 2–4 weeks.
• Elderly dosing: Initiate at the lower end (150 mg/day) and titrate slowly to minimize falls.
• Renal dosing schema: A simple mnemonic—“CrCl > 60 → 600 mg/day; 30–60 → 300 mg/day; < 30 → 150 mg/day.”
• Pregnancy risk profile: Though category C, the FDA has reputable data supporting use when other agents are ineffective; discuss alternatives.
• Smart dosing kits: Some manufacturers offer a 4‑in‑1 prefilled tablet system (one 24 mg, one 48 mg, one 75 mg, one 150 mg) to aid titration.
• Patient education: Emphasize the need to avoid alcohol and other CNS depressants until the side‑effect profile stabilizes.

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• *Prepared with current consensus guidelines and reference literature up to 2026.*