Gabapentin (Neurontin)

Overview: 

Brand name: Neurontin

Structure and Mechanism

  • 1-(aminomethyl)cyclohexaneacetic acid (C9H17NO2)
  • It is structurally related to gamma-aminobutyric acid (GABA).
  • However, does not modify GABA binding, is not converted into a GABA agonist, and does not inhibit GABA uptake/degradation
  • Instead, a binding site on a voltage-activated calcium channel subunit has been identified

Pharmacokinetics

  • Not appreciably metabolized in humans
  • Eliminated from the systemic circulation by renal excretion
  • Elimination half-life ≅ 5 to 7 hours
  • In elderly patients and those with impaired renal function, plasma clearance is reduced
  • Mean half-life increased from 6.5 h (CrCl >60 mL/min) to 52 h (CrCL <30 mL/min)
  • Gabapentin can be removed from plasma by hemodialysis
  • Bioavailability is not proportional to dose (i.e. bioavailability of gabapentin ≅ 60% (900mg), 47% (1200mg), 34% (2400mg), 33% (2600mg), and 27% (4800mg) per day, given in 3 divided doses. 

Medical Indications

  • In animal models of analgesia, gabapentin prevents allodynia and hyperalgesia.
  • Gabapentin is indicated for:
    • Neuropathic pain caused by postherpetic neuralgia 
    • Adjunctive therapy in the treatment of partial seizures with or without secondary generalization
    • Neuropathic pain caused by diabetic peripheral neuropathy and spinal cord injury 
    • Restless leg syndrome (gabapentin enacarbil)
  • Gabapentin is frequently used off-label for:
    • Neuropathy caused by other etiologies such as chronic regional pain syndrome (CRPS), cancer, multiple sclerosis, phantom limb pain, HIV
    • Vasomotor symptoms (i.e. hot flashes)
    • Acute pain
    • Mood disorder (e.g. anxiety, bipolar)

Dosing

  • Dosing ≅ 10-15 mg/kg/day in 3 divided doses
  • Typically, begin with 300mg qd and uptitrate 
  • Up to 3600mg qd: however, additional benefit for doses >1800 mg/day not demonstrated
  • Often dosed qhs or tid
  • Reduction with decreased CrCl (e.g. CKD, elderly)

Risks and Side Effects

  • Dizziness, somnolence, and peripheral edema
  • Suicidal ideation
  • Respiratory depression concomitant with other depressants (e.g. opioids, sedatives) 
  • Pregnancy Category C (fetotoxic in animal studies, limited human data)
  • Excreted into breast milk
  • Beers Criteria (2019)
  • Potential for withdrawal

ERAS Protocol

  • UCSF 600mg PO qhs for multiple services (e.g. breast, colorectal) 
References: 

Michael Verret et. al.; Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis. Anesthesiology 2020; 133:265–279 doi: https://doi.org/10.1097/ALN.0000000000003428

Straube  S, Derry  S, Moore  RA, Wiffen  PJ, McQuay  HJ. Single dose oral gabapentin for established acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008183. DOI: 10.1002/14651858.CD008183.pub2

Hah J, Mackey SC, Schmidt P, et al. Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial. JAMA Surg. 2018;153(4):303–311. doi:10.1001/jamasurg.2017.491

Author: 
Sekar Manoj