Gabapentin

Aka: Gabapentin, Neurontin

1. Precautions: Risk of Abuse
   1. Gabapentin and Pregabalin (Lyrica) are abused by patients on Opiates to potentiate CNS Opiate effects
   2. More than one quarter of Opiate patients have abused Gabapentin
   3. Pregabalin (Lyrica) is more potent with faster onset and has higher abuse potential than Gabapentin
   4. Lyrica is categorized as DEA Controlled Substance Class V (and Gabapentin in several states)
   5. Smith (2012) Br J Gen Pract 62(601):406-7 +PMID:22867659 [PubMed]
2. Indications
   1. Neuropathic pain (peripheral nerve syndromes)
      1. Diabetic Neuropathy
      2. Postherpetic Neuralgia
      3. Trigeminal Neuralgia
      4. Cancer Pain Management
   2. Multiple Sclerosis
   3. Parkinson's Disease
   4. Restless Legs Syndrome
      1. Effective in idiopathic RLS
         1. Happer (2001) Neurology 57(9):1717-9 [PubMed]
      2. Effective in RLS among Hemodialysis patients
         1. Thorp (2001) Am J Kidney Dis 38(1):104-108 [PubMed]
   5. Epilepsy
      1. Generalized Tonic Clonic Seizures (rarely used)
      2. Partial Seizures (adjunctive agent)
   6. Bipolar Disorder
   7. Anxiety Disorder
      1. Post-Traumatic Stress Disorder (PTSD)
      2. Social Phobia
      3. Generalized Anxiety Disorder
   8. Alcohol Dependence
      1. Doses of 600 mg orally three times daily appear to decrease Alcohol cravings
3. Safety
   1. Pregnancy Category C
   2. Excreted in Breast Milk
4. Mechanism
   1. GABA amino acid derivative (does not bind GABA-A or GABA-B receptors)
   2. Binds alpha2-delta1 subunit of Central Nervous System voltage-gated Calcium channels
   3. Decreases excitatory Neurotransmitter release and activity
5. Metabolism
   1. Bioavailability varies by dose
      1. Larger doses have lower bioavailability
      2. Divided doses result in better bioavailability
   2. Primarily renal excretion in its original form (not metabolized)
   3. Half-life: 5 to 7 hours
   4. Therapeutic Dose: 4-8 ug/ml
6. Adverse Effects: Standard Dosing
   1. Most common
      1. Sedation
      2. Dizziness
      3. Ataxia
   2. Other adverse effects
      1. Weight gain
      2. Nausea
      3. Fatigue
      4. Nystagmus
7. Adverse Effects: Overdose
   1. Acute Overdose: Sedative-Hypnotic effects
      1. Sleepy or lethargic
      2. Normal Vital Signs
   2. Chronic toxicity (especially with Renal Insufficiency)
      1. Progressive weakness
      2. Fatigue
      3. Altered Level of Consciousness
      4. Falls
8. Preparations: Newer related agents
   1. Pregabalin (Lyrica)
      1. Indicated in Neuropathy
      2. More potent than Gabapentin, and possibly less Fatigue
9. Dosing: Neuropathy in Adults
   1. Starting Dose
      1. Start at 300 mg orally at bedtime
      2. Advance to 300 mg orally three times daily (over 4-7 days)
      3. Plan to ultimately increase to 600 mg three times daily
      4. Patients tolerate starting 300 three times daily without titrating
      5. Fisher (2001) Neurology 56(6):743-8 [PubMed]
   2. Average Dose: 600 mg orally three times daily
   3. Maximum Dose: 1200 mg orally three times daily
      1. No increase in bioavailability above 1200 mg orally three times daily
      2. Minimal pain benefit above 1800 mg/day in most conditions studied
   4. Stopping (similar to Pregabalin)
      1. Taper off agent over 1 week or more
      2. Avoid stopping abruptly due to withdrawal symptoms
10. Dosing: Seizure Prophylaxis
    1. Age 3-12 years old
       1. Gabapentin 10-15 mg/kg (max 40 mg/kg) daily divided three times daily
    2. Age >12 years old
       1. Gabapentin 300-900 mg (max 1800) daily divided three times daily
11. Drug Interactions
    1. No significant Drug Interactions
    2. However, Renal Insufficiency results in drug accumulation
12. Disadvantages
    1. Low potency as antiepileptic
13. References
    1. (2016) Crit Dec Emerg Med 30(9):24
    2. Lapoint (2021) EM:Rap 21(6): 16-7