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Gabapentin

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Gabapentin, Neurontin, Horizant, Gralise, Gabapentinoid

  • See Also
  1. Pregabalin (Lyrica)
  • Definitions
  1. Gabapentinoid
    1. GABA derivatives that inhibit voltage-gated Calcium channels (at the a2d Subunit)
    2. Gabapentinoid examples include Gabapentin and Pregabalin
  • Indications
  1. Neuropathic pain (Peripheral Nerve syndromes)
    1. Diabetic Neuropathy
    2. Postherpetic Neuralgia (FDA approved)
    3. Trigeminal Neuralgia
    4. Cancer Pain Management
  2. Multiple Sclerosis
  3. Parkinson's Disease
  4. Fibromyalgia
  5. 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]
  6. Epilepsy
    1. Partial Seizures (adjunctive agent, FDA approved)
    2. Generalized Tonic Clonic Seizures (rarely used)
      1. Low potency as antiepileptic drug
      2. May worsen idiopathic Generalized Seizures
  7. Bipolar Disorder
  8. Anxiety Disorder
    1. Post-Traumatic Stress Disorder (PTSD)
    2. Social Phobia
    3. Generalized Anxiety Disorder
  9. Alcohol Dependence
    1. Doses of 600 mg orally three times daily appear to decrease Alcohol cravings
  10. Opioid Dependence
  • Efficacy
  1. Chronic Pain (NNT 4.3)
  2. Diabetic Neuropathy (NNT 2.9)
  3. Postherpetic Neuralgia (NNT 3.9)
  • Safety
  1. Pregnancy Category C
  2. Excreted in Breast Milk
  3. Safe in liver disease (not hepatically metabolized)
  4. Reduce dose in renal Impairment
  • Mechanism
  1. GABA Amino Acid derivative (does not bind GABA-A or GABA-B Receptors)
  2. Binds presynaptic alpha2-delta1 subunit of Central Nervous System voltage-gated Calcium channels
  3. Decreases excitatory Neurotransmitter release and activity
  • Metabolism
  1. Bioavailability varies by dose
    1. Larger doses have lower Bioavailability
    2. Divided doses result in better Bioavailability
  2. Half-Life: 5 to 7 hours
  3. Therapeutic Dose: 4-8 ug/ml
  4. Primarily renal excretion in its original form (not metabolized)
    1. Creatine Clearance >60 ml/min: Max 900 to 3600 mg/day
    2. Creatine Clearance 30 to 59 ml/min: Max 400 to 1400 mg/day
    3. Creatine Clearance 15 to 29 ml/min: Max 200 to 700 mg/day
    4. Creatine Clearance <15 ml/min: Max 100 to 300 mg/day
  • Adverse Effects
  • Standard Dosing
  1. Most common
    1. Sedation
    2. Dizziness
    3. Ataxia
  2. Other adverse effects
    1. Weight gain
    2. Peripheral Edema
    3. Nausea
    4. Fatigue
    5. Nystagmus
  3. Withdrawal symptoms
    1. Avoid stopping abruptly from higher doses (taper off)
  4. 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]
  5. Cardiovascular Events
    1. Single retrospective EHR chart review associated Gabapentin and Pregabalin with cardiovascular events
    2. Higher quality confirmatory studies are needed
    3. Pan (2022) Cardiovasc Diabetol 21(1):170 +PMID: 36050764 [PubMed]
  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
  • Preparations
  • Newer related agents
  1. Pregabalin (Lyrica)
    1. Indicated in Neuropathy
    2. More potent than Gabapentin, and possibly less Fatigue
  2. Gabapentin extended release (Gralise)
    1. Taken once daily in doses 300 to 1800 mg for Postherpetic Neuralgia
    2. Avoid in patients with Creatinine Clearance <30 ml/min or on Hemodialysis
  3. Gabapentin extended release (Horizant)
    1. Taken 600 mg orally daily (restless legs) to twice daily (Postherpetic Neuralgia)
  1. See metabolism above for maximum dosing in renal Impairment
  2. Starting Dose
    1. Start Gabapentin 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]
  3. Average Dose: 600 mg orally three times daily
  4. 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
  5. Stopping (similar to Pregabalin)
    1. Taper off agent over 1 week or more
    2. Avoid stopping abruptly due to withdrawal symptoms
  1. See metabolism above for maximum dosing in renal Impairment
  2. Not FDA approved (off label use)
  3. Day 1: Give 5 mg/kg orally at bedtime
  4. Day 2: Give 5 mg/kg orally twice daily
  5. Day 3: Give 5 mg/kg orally three times daily
  6. Titrate to Target dose: 8 to 35 mg/kg/day divided three times daily
  1. See metabolism above for maximum dosing in renal Impairment
  2. Child (age 3-12 years old)
    1. Start 10-15 mg/kg/day divided three times daily
    2. Titrate to Target dose: 25 to 35 mg/kg/day (40 mg/kg/day if age 3 to 4 years old) divided three times daily
    3. Maximum: 40 mg/kg/day (up to 3600 mg/day)
  3. Adult (and children age >12 years old)
    1. Start 300 mg orally three times daily
    2. Typical dose 300 to 600 mg orally three times daily
    3. Maximum: 1800 to 2400 mg are well tolerated (3600 mg/day is absolute maximum)
  • Dosing
  • Posthepetic Neuralgia
  1. See Postherpetic Neuralgia
  2. See metabolism above for maximum dosing in renal Impairment
  3. Gabapentin
    1. Day 1: 300 mg orally once
    2. Day 2: 300 mg orally twice daily
    3. Day 3: 300 mg orally three times daily
    4. Titrate as needed for reduction in pain (up to 1800 mg/day)
  4. Long Acting Agents
    1. Gralise once daily in doses titrated up from 300 to 1800 mg over 2 weeks for Postherpetic Neuralgia
    2. Horizant started at 600 mg orally daily for 3 days, then 600 mg orally twice daily
  • Dosing
  • Miscellaneous Other Use
  1. See metabolism above for maximum dosing in renal Impairment
  2. Mostly off label (non-FDA approved usage)
  3. Restless Leg Syndrome
    1. Gabapentin 300 mg orally 2 hours before bed
    2. Horizant 600 mg orally at dinner
  4. Alcohol Dependence
    1. Target dose 600 mg orally three times daily (start lower and titrate to dose)
  5. Migraine Prophylaxis
    1. Start 300 mg orally at bedtime
    2. Titrate to 1800 to 2400 mg/day divided three times daily
  6. Hot Flushes
    1. Take 300 mg orally three times daily
  • Drug Interactions
  1. No significant Drug Interactions
  2. However, Renal Insufficiency results in drug accumulation
  • Resources
  1. Gabapentin (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee9ad9ed-6d9f-4ee1-9d7f-cfad438df388
  2. Gralise (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7d12b4e9-ed44-43c0-9e46-f6c195300f03
  3. Horizant (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c486fc7-c8c4-4c6c-b30c-366dabaeaadd
  • References
  1. (2016) Crit Dec Emerg Med 30(9):24
  2. (2022) Presc Lett, Resource #361206, Antiseizure Medications
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  4. LoVecchio (2022) Crit Dec Emerg Med 36(4): 36
  5. Lapoint (2021) EM:Rap 21(6): 16-7
  6. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
  7. Wiffen (2005) Cochrane Database Syst Rev (3):CD005452 +PMID: 16034978 [PubMed]