- Last edited on June 7, 2023
Gabapentin (Neurontin)
Primer
Gabapentin (Trade name: Neurontin) is an anticonvulsant. It is commonly also used off-label for anxiety disorders, restless leg syndrome, and in alcohol use disorder. It is structurally similar to GABA but does not directly bind to GABA receptors.
Pharmacokinetics
See also article: Introduction to Pharmacology
Pharmacokinetics of Gabapentin
Absorption | Bioavailabiltiy of 59%. Tmax = 2-4 hours |
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Distribution | High volume of distribution (58L), less than 3% of gabapentin is bound to plasma proteins |
Metabolism | Not metabolized to a significant extent in humans. |
Elimination | Solely renal excretion as unchanged drug, and can be removed from plasma by hemodialysis. |
Half-life | 5-7 hours |
See also article: Cytochrome (CYP) P450 Metabolism
Gabapentin: Cytochrome P450 Metabolism
Substrate of (Metabolized by) | Not metabolized in humans |
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Induces | - |
Inhibits | - |
Pharmacodynamics
Mechanism of Action
- Gabapentin is designed as GABA analog (similar to pregabalin), which means it binds to the α2δ (alpha-2-delta) subunit of presynaptic voltage-sensitive Ca2+ channels (VSCCs), and block the release of excitatory neurotransmitters such as glutamate.
- This changes the VSCC conformation to reduce calcium influx and thus reduce excessive stimulation of postsynaptic receptors.
Toxicity
Indications
- Seizure disorders
- Anxiety disorders, sleep disorders, pain syndromes
Dosing
Dosing for Gabapentin
Starting | |
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Titration | |
Maximum | |
Taper |
Formulations
- Gabapentin comes in oral formulation.
Monitoring
Contraindications
Absolute
Relative
Drug-Drug Interactions
Side Effects
- Gabapentin can also cause myoclonus (especially in the setting of acute kidney injuries when gabapentin is not able to be cleared).[1]
Adverse Events
Withdrawal
- Withdrawal may occur after prolonged use of gabapentin
Misuse
- Gabapentin is an approved treatment as an adjunctive therapy in the management of epilepsy. However, it is most commonly prescribed off-label for other conditions, including anxiety, alcohol use disorder, and chronic pain.[2]
- Gabapentin misuse is increasing (oral, intranasal, and intravenous). Misuse can produce anxiolytic effects and a euphoria that is similar opioid misuse. Gabapentin can cause respiratory depression, physiologic dependence, and withdrawal symptoms on cessation (including diaphoresis, anxiety, confusion, and seizures).
- Patients who are co-prescribed gabapentin and opioids are at a significantly higher risk of death compared with those prescribed opioids alone.[3]
Clinical Pearls
Special Populations
Geriatric
See main article: Geriatric Pharmacology
Pediatric
See main article: Pediatric Pharmacology
Obstetric and Fetal
See main article: Obstetric and Fetal Pharmacology
Medically Ill
See main article: Psychotropic Dosing in the Medically Ill
Resources
Research
References
1)
Desai, A., Kherallah, Y., Szabo, C., & Marawar, R. (2019). Gabapentin or pregabalin induced myoclonus: A case series and literature review. Journal of Clinical Neuroscience, 61, 225-234.