Gabapentin

Aka: Gabapentin, Neurontin, Horizant, Gralise, Gabapentinoid

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II. Definitions

  1. Gabapentinoid
    1. GABA derivatives that inhibit voltage-gated Calcium channels (at the a2d Subunit)
    2. Gabapentinoid examples include Gabapentin and Pregabalin

III. 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

IV. Efficacy

  1. Chronic Pain (NNT 4.3)
  2. Diabetic Neuropathy (NNT 2.9)
  3. Postherpetic Neuralgia (NNT 3.9)

V. Safety

  1. Pregnancy Category C
  2. Excreted in Breast Milk
  3. Safe in liver disease (not hepatically metabolized)
  4. Reduce dose in renal Impairment

VI. 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

VII. 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

VIII. 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]

IX. 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

X. 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)

XI. Dosing: Neuropathy in Adults

  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

XII. Dosing: Neuropathy in Children

  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

XIII. Dosing: Partial Seizure Prophylaxis

  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)

XIV. 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

XV. 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

XVI. Drug Interactions

  1. No significant Drug Interactions
  2. However, Renal Insufficiency results in drug accumulation

XVII. 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

XVIII. 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]

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Related Studies

Cost: Medications

gabapentin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GABAPENTIN 100 MG CAPSULE Generic $0.03 each
GABAPENTIN 250 MG/5 ML SOLN Generic $0.09 per ml
GABAPENTIN 300 MG CAPSULE Generic $0.04 each
GABAPENTIN 400 MG CAPSULE Generic $0.06 each
GABAPENTIN 600 MG TABLET Generic $0.10 each
GABAPENTIN 800 MG TABLET Generic $0.13 each
neurontin (on 7/19/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
NEURONTIN 300 MG CAPSULE Generic $0.04 each
NEURONTIN 600 MG TABLET Generic $0.10 each
horizant (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
HORIZANT ER 300 MG TABLET $14.98 each
HORIZANT ER 600 MG TABLET $14.94 each
gralise (on 5/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GRALISE ER 300 MG TABLET $9.76 each
GRALISE ER 600 MG TABLET $9.79 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Ontology: gabapentin (C0060926)

Definition (NCI_NCI-GLOSS) A substance that is being studied as a treatment for relieving hot flashes in women with breast cancer. It belongs to the family of drugs called anticonvulsants.
Definition (NCI) A synthetic analogue of the neurotransmitter gamma-aminobutyric acid with anticonvulsant activity. Although its exact mechanism of action is unknown, gabapentin appears to inhibit excitatory neuron activity. This agent also exhibits analgesic properties. (NCI04)
Definition (CSP) cyclohexananeacetic acid originally used as an anticonvulsant, found to have diverse CNS depressant actions.
Definition (PDQ) A synthetic analogue of the neurotransmitter gamma-aminobutyric acid with anticonvulsant activity. Although its exact mechanism of action is unknown, gabapentin appears to inhibit excitatory neuron activity. This agent also exhibits analgesic properties. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38402&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38402&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1108" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C040029
SnomedCT 108402001, 386845007
LNC LP17989-2, MTHU012288
English 1-(aminomethyl)cyclohexaneacetic acid, 1-(aminomethyl)cyclohexaneacetic Acid, gabapentin (medication), GABAPENTIN, gabapentin [Chemical/Ingredient], Convalis, gabapentin, Gabapentin, Gabapentin (product), Gabapentin (substance)
Spanish gabapentina (producto), gabapentina (sustancia), gabapentina
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Neurontin (C0678176)

Definition (CHV) a kind of pain relieving drug
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C040029
English Neurontin, neurontin, Aventis brand of gabapentin, Parke Davis brand of gabapentin, Pfizer brand of gabapentin, Warner-Lambert brand of gabapentin
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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