Version July 2025
Dosage guidance:
Clinical considerations: Neonatal data are limited regarding the incidence of withdrawal upon discontinuation; avoid abrupt discontinuation with prolonged therapy (use >1 week); weaning has been recommended (Ref).
Pain and agitation, refractory: Limited data available; optimal dose not established. Dosing based on two retrospective studies that described individual NICU experiences with gabapentin.
Neonates: Oral: 2.5 to 10 mg/kg/day divided every 8 hours; titrate dose (eg, every 3 to 5 days) as needed to effect; maximum reported dose: 35 mg/kg/day; studies reported gabapentin was well tolerated and resulted in a reduction in N-PASS scores and decreased need for opioids, benzodiazepines, and/or alpha agonists (Ref).
Dosage guidance:
Dosing: Pediatric doses presented as mg/kg/day and mg/kg/dose; use precaution.
Seizures, partial onset; adjunctive therapy: Note: Do not exceed 12 hours between doses with 3-times-daily dosing. If gabapentin is discontinued or if another antiseizure medication is added to therapy, it should be done slowly over a minimum of 1 week.
Children 3 to <12 years: Immediate release:
Initial: Oral: 10 to 15 mg/kg/day divided into 3 doses daily; titrate dose upward over ~3 days.
Maintenance usual dose:
Children 3 to 4 years: Oral: 40 mg/kg/day divided into 3 doses daily; maximum daily dose: In one long-term study, doses up to 50 mg/kg/day were well-tolerated.
Children 5 to <12 years: Oral: 25 to 35 mg/kg/day divided into 3 doses daily; maximum daily dose: In one long-term study, doses up to 50 mg/kg/day were well-tolerated.
Children ≥12 years and Adolescents: Immediate release: Oral: Initial: 300 mg 3 times daily; titrate dose upward if needed; usual maintenance dose: 900 to 1,800 mg/day divided into 3 doses daily; doses up to 2,400 mg/day divided into 3 doses daily are well tolerated long-term; maximum daily dose: Doses up to 3,600 mg/day have been tolerated in short-term studies.
Neuropathic pain: Limited data available: Children and Adolescents: Immediate release: Oral: Initial: 5 mg/kg/dose at bedtime, maximum dose: 300 mg/dose; day 2: Increase to 5 mg/kg/dose twice daily, maximum dose: 300 mg/dose; day 3: Increase to 5 mg/kg/dose 3 times daily, maximum dose: 300 mg/dose; further titrate with dosage increases (not frequency) to effect; usual dosage range: 8 to 35 mg/kg/day divided into 3 doses daily; maximum daily dose: 3,600 mg/day; do not exceed 12 hours between doses with 3-times-daily dosing; a lower initial dose may be considered if concurrent analgesics are also sedating (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral: Immediate release:
Children <12 years: There are no dosing adjustments provided in the manufacturer's labeling (has not been studied).
Children ≥12 years and Adolescents: See table.
|
CrCl |
Total Daily Dose Range |
Dosage Regimens (Maintenance Doses) | ||||
|---|---|---|---|---|---|---|
|
a CrCl <15 mL/minute: Reduce daily dose in proportion to creatinine clearance. | ||||||
|
b Supplemental dose should be administered after each 4 hours of hemodialysis (patients on hemodialysis should also receive maintenance doses based on renal function as listed in the upper portion of the table). | ||||||
|
≥60 mL/minute |
900 to 3,600 mg/day |
300 mg 3 times daily |
400 mg 3 times daily |
600 mg 3 times daily |
800 mg 3 times daily |
1,200 mg 3 times daily |
|
>30 to 59 mL/minute |
400 to 1,400 mg/day |
200 mg twice daily |
300 mg twice daily |
400 mg twice daily |
500 mg twice daily |
700 mg twice daily |
|
>15 to 29 mL/minute |
200 to 700 mg/day |
200 mg daily |
300 mg daily |
400 mg daily |
500 mg daily |
700 mg daily |
|
15 mL/minutea |
100 to 300 mg/day |
100 mg daily |
125 mg daily |
150 mg daily |
200 mg daily |
300 mg daily |
|
Hemodialysisb |
Posthemodialysis Supplemental Dose | |||||
|
125 mg |
150 mg |
200 mg |
250 mg |
350 mg | ||
There are no dosage adjustments provided in the manufacturer's labeling; however, adjustment not necessary since gabapentin is not hepatically metabolized.
(For additional information see "Gabapentin: Drug information")
Dosage guidance:
Safety: For patients with respiratory disease, initiate therapy at the lowest dose (Ref).
Alcohol use disorder, moderate to severe (alternative agent) (off-label use):
Note: Gabapentin is suggested by some experts as an alternative when first-line agents cannot be used (Ref). Gabapentin may be misused by some patients with substance use disorders; evaluate for risk and signs of addiction and dependence (Ref).
Immediate release: Oral: Initial: 300 mg once daily; increase dose based on response and tolerability in increments of 300 mg every 1 to 2 days up to a target dose of 600 mg 3 times daily (Ref). Some experts consider alternative therapies if goals are not met within 6 months of treatment (Ref).
Alcohol withdrawal (off-label use):
Note: Withdrawal will progress at different rates in some patients; flexibility in dosing and duration is warranted (Ref). Regimens vary and depend on withdrawal history, degree of current withdrawal symptoms, quantity of alcohol consumption, concomitant medications for breakthrough symptoms, and whether the patient is treated inpatient or in the ambulatory setting. For example, in an inpatient study that enrolled patients with Clinical Institute Withdrawal Assessment (CIWA) scores >15 and offered no as-needed medications for breakthrough withdrawal symptoms, 3.2 g in divided doses was offered on day 1 of treatment (Ref). Many facilities only treat alcohol withdrawal in the ambulatory setting if CIWA score is ≤15 and there is no history of withdrawal seizures or delirium tremens (Ref). The following are two suggested regimens.
CIWA score <10: Immediate release: Oral: Initial: 300 mg every 6 hours on day 1, then 300 mg every 8 hours on day 2, then 300 mg every 12 hours on day 3, then 300 mg at night on day 4. In addition to scheduled doses, provide one additional as-needed 300 mg dose per day for breakthrough withdrawal symptoms (Ref).
CIWA score 10 to 18 (alternative agent) (Ref): Immediate release: Oral: Initial: 300 to 400 mg 3 times daily on days 1 through 3, then 300 to 400 mg twice daily on day 4, then discontinue. For breakthrough symptoms during days 1 through 4, consider providing single doses of 100 mg, which may be administered up to 3 times daily, and a 300 mg dose reserved for the evening (Ref).
Cough, chronic refractory (alternative agent) (off-label use):
Note: Reserve for patients with cough lasting >8 weeks who have had negative responses to treatments for asthma, gastroesophageal reflux disease, and rhinitis (Ref).
Immediate release: Oral: Initial: 300 mg once daily (Ref); if significant somnolence develops, some experts recommend decreasing dose to 100 mg once daily (Ref). May increase dose gradually based on response and tolerability in increments of 300 mg to a maximum dose of 900 mg twice daily (Ref). Re-evaluate therapeutic need after 6 months (Ref).
Essential tremor (alternative agent) (off-label use):
Note: Reserve use for patients with inadequate response to preferred therapy; may be used as adjunctive or monotherapy (Ref).
Immediate release: Oral: Initial: 100 to 300 mg three times daily; may increase total daily dose in 300 mg/day increments based on response and tolerability at intervals of 4 to 7 days up to 1.2 g/day in 3 divided doses (Ref).
Fibromyalgia (alternative agent) (off-label use):
Note: For patients who do not respond to or tolerate preferred agents (Ref):
Immediate release: Oral: Initial: 100 to 300 mg once daily at bedtime; increase dose gradually based on response and tolerability every 1 to 4 weeks to a target dose of 1.2 to 2.4 g/day in divided doses (Ref).
Generalized anxiety disorder (alternative agent) (off-label use):
Note: Adjunctive therapy for short-term symptom relief until concurrent therapy is effective (eg, 4 to 6 weeks, followed by tapering). Long-term augmentation may be considered when preferred treatments (eg, serotonin reuptake inhibitors) are partially effective (Ref).
Immediate release: Oral: Initial: 300 mg/day; may increase dose gradually based on response and tolerability up to 2.4 g/day, in 2 to 3 divided doses (Ref). Note: In patients sensitive to side effects, some experts suggest a lower starting dose (eg, 100 mg/day) and more gradual titration (Ref).
Hiccups (off-label use ): Immediate release: Oral: Usual dose range: 300 mg to 1.2 g/day in 3 to 4 divided doses (Ref). Can be discontinued the day after hiccups subside; long-term therapy may be warranted for persistent or relapsing hiccups (eg, palliative care) (Ref). Note: In patients with refractory hiccups, may use in combination with a proton pump inhibitor, baclofen, or metoclopramide (Ref).
Neuropathic pain:
General dosing recommendations (for other than postherpetic neuralgia) (off-label use):
Note: For chronic use, an adequate trial with gabapentin may require 2 months or more (Ref). For critically ill patients with neuropathic pain, gabapentin may be a useful component of multimodal pain control (Ref).
Immediate release: Oral: Initial: 100 to 300 mg 1 to 3 times daily (Ref); increase dose based on response and tolerability to a target dose range of 300 mg to 1.2 g 3 times daily (Ref).
Extended release: Oral: Initial: 300 mg at bedtime; increase dose based on response and tolerability to a target dose of 900 mg to 3.6 g once daily (Ref).
Panic disorder:
Note: Reserve for augmentation of selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor in patients who need rapid symptom relief or who only experience partial relief of symptoms on antidepressant monotherapy (Ref).
Immediate release: Oral: 200 mg three times daily; may increase daily dose based on response and tolerability in 600 to 900 mg increments at weekly intervals up to 3.6 g/day (Ref).
Postherpetic neuralgia:
Immediate release: Oral: 300 mg once on day one, 300 mg twice daily on day 2, and 300 mg 3 times daily on day 3, then increase as needed up to 1.8 to 3.6 g/day in divided doses. Additional benefit of doses >1.8 g/day has not been established.
Extended release: Oral: Initial: 300 mg once daily; increase by 300 mg each day up to 900 mg once daily. Further increase as needed up to 1.8 g once daily. Additional benefit of doses >1.8 g/day has not been established.
Pruritus, chronic (alternative agent) (off-label use):
Note: For patients with pruritus resistant to preferred therapies (Ref):
Neuropathic (eg, brachioradial pruritus, notalgia paresthetica) or malignancy-related pruritus: Immediate release: Oral: Initial: 300 mg/day in 1 to 3 divided doses; increase dose based on response and tolerability up to 1.8 g/day in divided doses (Ref). Higher doses up to 3.6 g/day have been used in oncology populations (Ref).
Uremic pruritus: Immediate release: Oral: Initial: 100 mg after dialysis on hemodialysis days; may increase dose based on response and tolerability up to 300 mg after dialysis on hemodialysis days (Ref).
Restless legs syndrome (off-label use): Immediate release: Oral: Initial: 100 to 300 mg once daily 2 hours before bedtime; may increase dose every 1 to 2 weeks until symptom relief is achieved (usual dosage: 300 mg/day to 1.8 g/day in divided doses; maximum single dose: 1.2 g). Suggested maintenance dosing schedule for doses ≥600 mg/day: One-third of total daily dose given midday, remaining two-thirds of the total daily dose given in the evening (Ref).
Seizures, focal (partial) onset (adjunctive agent):
Note: Avoid use in myoclonic or generalized nonmotor (absence) seizures due to potential to worsen generalized convulsion (Ref).
Immediate release: Oral: Initial: 100 to 300 mg 3 times daily; increase dose based on response and tolerability. Usual dosage: 300 to 600 mg 3 times daily; doses up to 2.4 g/day and 3.6 g/day have been tolerated in long-term and short-term clinical studies, respectively (Ref).
Social anxiety disorder (alternative agent) (off-label use):
Note: Reserve for patients who do not tolerate or respond to preferred agents (Ref):
Immediate release: Oral: Initial: 300 mg twice daily; increase dose based on response and tolerability in increments of no more than 300 mg/day up to a maximum of 3.6 g/day in 3 divided doses (Ref). Some experts recommend initiating with 100 mg 3 times daily in patients with respiratory disease (Ref).
Vasomotor symptoms associated with menopause (alternative agent) (off-label use):
Note: Consider for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy (Ref).
Immediate release: Oral: Initial: 100 to 300 mg once daily at bedtime (Ref); increase gradually (eg, over 3 to 12 days) based on response and tolerability up to 600 mg to 2.4 g/day in 2 to 3 divided doses (Ref). Some experts suggest gabapentin for patients whose symptoms occur primarily at night and favor a maximum dose of 900 mg to 1.2 g, given as one dose at bedtime (Ref).
Extended release: Oral: Initial: 600 mg once daily at bedtime; increase gradually (eg, 600 mg every 3 days) to target dose of 600 mg in the morning and 1.2 g at bedtime (Ref).
Discontinuation of therapy: In patients receiving gabapentin chronically, unless safety concerns require a more rapid withdrawal, gabapentin should be withdrawn gradually over ≥1 week to minimize the potential of increased seizure frequency (in patients with epilepsy) or other withdrawal symptoms (eg, confusion, irritability, tachycardia, diaphoresis) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Oral: Immediate release:
Note: Initial doses of gabapentin should be conservative and titrated based on effectiveness and tolerability.
|
CrCl (mL/minute)c |
Approximate Maintenance Dose Adjustment |
Maximum Maintenance Dose |
|---|---|---|
|
aChoose normal dose based on indication (see Adult dosing), then choose the adjusted dose from the column corresponding to the patient's CrCl. | ||
|
bExpert opinion derived from Blum 1994, Davison 2014, Davison 2019, manufacturer's labeling. | ||
|
cEstimation of renal function for dosing adjustments should be done using the Cockcroft Gault formula. | ||
|
>79 |
No dose adjustment necessary |
3,600 mg/day in 3 divided doses |
|
50 to 79 |
No dose adjustment necessary, not to exceed 1,800 mg/day |
1,800 mg/day in 3 divided doses |
|
30 to 49 |
~50% reduction |
900 mg/day in 2 to 3 divided doses |
|
15 to 29 |
~75% reduction |
600 mg/day in 1 to 2 divided doses |
|
<15 |
~90% reduction |
300 mg/day in 1 dose |
Hemodialysis, intermittent (thrice weekly): Dialyzable (50% over 4 hours (Ref)):
Initial: 100 mg 3 times per week after hemodialysis. Titrate to effect up to 300 mg 3 times per week given after hemodialysis on dialysis days (Ref).
Note: Some experts recommend cautious titration to a maximum of 300 mg/day in select patients requiring additional pain control (Ref).
Peritoneal dialysis:
Initial: 100 mg every other day. Titrate to effect up to 300 mg every other day (Ref).
Note: Some experts recommend cautious titration to a maximum of 300 mg/day in select patients requiring additional pain control (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or approximately 1,500 to 3,000 mL/hour) unless otherwise noted.
CVVH/CVVHD/CVVHDF:
Note: Dosing based on expert opinion; no evidence available. Pharmacokinetic characteristics and one case report suggest gabapentin is cleared by CRRT (Ref).
Initial: 100 mg twice daily and titrate to effect. Suggested maximum dose: 300 mg twice daily.
Oral: Extended release:
Note: Follow initial dose titration schedule if treatment naive. Estimation of renal function for dosing adjustments should be done using the Cockcroft-Gault formula. Renally adjusted dose recommendations are based on doses up to 1.8 g/day.
CrCl ≥60 mL/minute: Oral: No dosage adjustment necessary.
CrCl >30 to 59 mL/minute: Oral: 600 mg to 1.8 g once daily; dependent on tolerability and clinical response.
CrCl <30 mL/minute: Use is not recommended.
End-stage renal disease requiring hemodialysis: Use is not recommended.
Peritoneal dialysis: Use is not recommended.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Initial doses of gabapentin should be conservative and titrated based on effectiveness and tolerability. The following recommendations are based on the use of IR formulations of gabapentin only; there are insufficient data to make dosage recommendations for the ER formulations in patients with liver impairment.
Liver impairment prior to treatment initiation:
Initial or dose adjustment in patients with preexisting liver cirrhosis :
Note: Use with caution in patients with hepatic encephalopathy, kidney impairment, or concomitant use of other CNS depressants (Ref).
Child-Turcotte-Pugh class A: Oral: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B and C: Immediate release: Oral: Initial: ≤300 mg per day in 1 to 3 divided doses; may titrate as tolerated to the usual indication-specific maximum recommended dose (Ref).
Liver impairment developing in patient already receiving gabapentin:
Chronic disease progression (eg, outpatient):
Note: Use with caution in patients with hepatic encephalopathy, kidney impairment, or concomitant use of CNS depressants (Ref).
Baseline to Child-Turcotte-Pugh class A: Oral: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class B and C: Oral: No dosage adjustment necessary (Ref).
Acute worsening of liver function (eg, requiring hospitalization):Consider an initial 50% reduction in daily dose to mitigate signs and symptoms associated with hepatic encephalopathy, especially if patient presents with concurrent kidney insufficiency (Ref). If discontinuation of gabapentin is necessary, a more rapid taper (eg, 50% reduction in daily dose every 3 to 4 days) while hospitalized with frequent monitoring for withdrawal is recommended (Ref).
Gabapentin may cause dose-dependent CNS depression and present as dizziness and/or drowsiness. In addition, serious, life-threatening, and fatal respiratory depression may occur; most cases occur with concomitant use of CNS depressants (especially opioids) in the setting of underlying respiratory impairment or in older patients (Ref). CNS depression may impair physical or mental abilities and result in accidental injury, including falls.
Mechanism: Dose-related; related to pharmacologic action (ie, structurally related to GABA)
Onset: Varied; timing impacted by concomitant use of medications known to cause CNS depression (eg, opioids) (Ref)
Risk factors:
• Concomitant use of alcohol or other CNS depressants (eg, opioids, benzodiazepines, antidepressants, antihistamines) (Ref)
• Patients with underlying respiratory impairment (Ref)
• Older patients (Ref)
Anaphylaxis or angioedema may occur. Signs and symptoms may include dyspnea, swelling of the lips, throat, and tongue, and hypotension (manufacturer’s labeling).
Mechanism: Non-dose-related; immunologic. In general, anaphylaxis is an IgE-mediated reaction (Ref).
Onset: Rapid; most anaphylactic reactions occur within minutes to hours of administration (Ref).
Risk factors:
• Prior history of immediate hypersensitivity reaction to gabapentin. Note: It is unknown whether cross-reactivity exists between gabapentin and pregabalin, given their similar structures. If an agent with similar structure is prescribed in a patient with a documented allergy to this drug, the possibility of cross-reactivity should be considered.
Isolated cases of dermatologic reactions, including maculopapular skin rash, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous pemphigoid, erythema multiforme, and hypersensitivity angiitis have been reported (Ref).
Mechanism: Non-dose-related; immunologic; Delayed hypersensitivity reactions are mediated by T-cells or antibodies other than IgE (eg, IgG-mediated, such as some cytopenias) (Ref). Severe cutaneous adverse reactions (SCARs) are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).
Onset: Varied; type IV reactions are delayed hypersensitivity reactions that typically occur days to weeks after drug exposure, but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).
Risk factors:
• Prior history of delayed hypersensitivity reaction to gabapentin. Note: It is unknown whether cross-reactivity exists between gabapentin and pregabalin, given their similar structures. If an agent with similar structure is prescribed in a patient with a documented allergy to this drug, the possibility of cross-reactivity should be considered. Gabapentin is usually considered a safe agent for patients with a previous history of drug allergies to other antiseizure medications (Ref).
Neuropsychiatric adverse reactions have occurred in pediatric patients (ages 3 to 12 years) with epilepsy, including emotional lability; hostility (eg, aggressive behaviors); changes in behavior and thinking (eg, concentration problems, changes in school performance); and hyperkinetic muscle activity (eg, restlessness, hyperactivity). In addition, agitation has been reported following use for neuropathic pain in adult patients with cognitive impairment secondary to brain injury (Ref).
Mechanism: Non-dose-related; exact mechanism not established; one theory is gabapentin results in disinhibition similar to what is seen following benzodiazepine use (Ref).
Risk factors:
• Children with intellectual disabilities and attention-deficit/hyperactivity disorders (Ref).
Antiseizure medications (ASMs) have been associated with suicidal ideation and suicidal tendencies. However, the FDA meta-analysis has been criticized due to several important limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some ASMs (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as postictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref). In one retrospective cohort study, gabapentinoids were associated with an increased risk for suicidal behavior and pregabalin was associated with a higher risk as compared to gabapentin; however, the impact of confounding variables (eg, alcohol use, illicit drug use) could not be fully elucidated (Ref).
Mechanism: Non–dose-related. Exact mechanism not established; one theory is antiseizure medications lower the threshold for manifesting psychiatric symptoms in patients susceptible to psychiatric disorders or antiseizure-induced disinhibition and impulsiveness, thereby influencing and promoting suicidal acts (Ref).
Onset: Varied; peak incidence of suicidality across antiseizure medications (not specific to individual agents) has been noted to occur between 1 and 12 weeks of therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.
Risk factors:
• Preexisting risk factors for suicidal thoughts and behaviors (including epilepsy)
• Prior history of psychiatric disorders or aggressive behaviors (Ref), including history of depression (Ref)
• Use in conditions other than epilepsy (eg, chronic pain conditions) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. [IR = Immediate Release, ER = Extended Release]
>10%:
Infection: Viral infection (IR, children: 11%)
Nervous system: Ataxia (IR, adolescents and adults: 1% to 13%), dizziness (IR, adolescents and adults: 17% to 28%; ER, adults: 11%; IR, children: 3%) (table 1), drowsiness (IR, adolescents and adults: 19% to 21%; IR, children: 8%; ER, adults: 5%) (table 2), fatigue (IR, adolescents and adults: 11%; IR, children: 3%)
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
2% |
Children |
IR |
Epilepsy |
119 |
128 |
|
17% |
7% |
Adolescents & adults |
IR |
Epilepsy |
543 |
378 |
|
28% |
8% |
Adults |
IR |
Postherpetic neuralgia |
336 |
227 |
|
11% |
2% |
Adults |
ER |
Postherpetic neuralgia |
359 |
364 |
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
8% |
5% |
Children |
IR |
Epilepsy |
119 |
128 |
|
19% |
9% |
Adolescents & adults |
IR |
Epilepsy |
543 |
378 |
|
21% |
5% |
Adults |
IR |
Postherpetic neuralgia |
336 |
227 |
|
5% |
3% |
Adults |
ER |
Postherpetic neuralgia |
359 |
364 |
1% to 10%:
Cardiovascular: Hypertension (ER, adults: >1%), peripheral edema (adolescents and adults: 2% to 8%), vasodilation (IR, adolescents and adults: 1%)
Dermatologic: Excoriation of skin (IR, adolescents and adults: 1%), skin rash (ER, adults: >1%)
Endocrine & metabolic: Hyperglycemia (IR, adults: 1%), weight gain (2% to 3%)
Gastrointestinal: Constipation (adolescents and adults: 1% to 4%), dental disease (IR, adolescents and adults: 2%), diarrhea (IR, adults: 6%), dyspepsia (adolescents and adults: 1% to 2%), nausea (IR: ≤8%; ER, adults: >1%), viral gastroenteritis (ER, adults: >1%), vomiting (IR: ≤8%), xerostomia (adolescents and adults: ≤5%)
Genitourinary: Erectile dysfunction (IR, adolescents and adults: 2%), urinary tract infection (ER, adults: 2%)
Infection: Herpes zoster infection (ER, adults: >1%), infection (IR, adults: 5%)
Nervous system: Abnormal gait (IR, adults: 2%), amnesia (IR, adolescents and adults: 2%), asthenia (IR, adults: 6%), changes in thinking (IR, adolescents and adults: 2% to 3%) (table 3), confusion (ER, adults: >1%), depression (IR, adolescents and adults: 2%), dysarthria (IR, adolescents and adults: 2%), emotional lability (IR, children: 4% to 6%) (table 4), hostility (IR, children: 5% to 8%) (table 5), lethargy (ER, adults: 1%), memory impairment (ER, adults: >1%), pain (ER, adults: 1%), status epilepticus (IR, adolescents and adults: 2%), tremor (IR, adolescents and adults: 7%), vertigo (ER, adults: 1%)
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
1% |
Adolescents & adults |
IR |
Epilepsy |
543 |
378 |
|
3% |
0% |
Adults |
IR |
Postherpetic neuralgia |
336 |
227 |
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
6% |
1% |
Children |
IR |
Epilepsy |
N/A |
N/A |
|
4% |
2% |
Children |
IR |
Epilepsy |
119 |
128 |
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
8% |
2% |
Children |
IR |
Epilepsy |
119 |
128 |
|
5% |
1% |
Children |
IR |
Epilepsy |
N/A |
N/A |
Neuromuscular & skeletal: Back pain (adolescents and adults: 2%), hyperkinetic muscle activity (IR, children: 3% to 5%) (table 6), joint swelling (ER, adults: >1%), limb pain (ER, adults: 2%)
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
5% |
3% |
Children |
IR |
Epilepsy |
N/A |
N/A |
|
3% |
1% |
Children |
IR |
Epilepsy |
119 |
128 |
Ophthalmic: Amblyopia (IR: 3% to 4%), conjunctivitis (IR, adults: 1%), diplopia (IR, adolescents and adults: 1% to 6%), nystagmus disorder (IR, adolescents and adults: 8%)
Otic: Otitis media (IR, adults: 1%)
Respiratory: Bronchitis (IR, children: 3%), cough (IR, adolescents and adults: 2%), dry throat (IR, adolescents and adults: ≤2%), nasopharyngitis (ER, adults: 3%), pharyngitis (IR, adolescents and adults: 1% to 3%), pneumonia (ER, adults: >1%), respiratory tract infection (IR, children: 3%), upper respiratory tract infection (ER, adults: >1%)
Miscellaneous: Accidental injury (IR, adults: 3%) (table 7), fever (IR, children: 10%; ER, adults: >1%)
|
Drug (Gabapentin) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Gabapentin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
3% |
1% |
Adults |
IR |
Postherpetic neuralgia |
336 |
227 |
Postmarketing:
Cardiovascular: Cardiomyopathy (Ref)
Dermatologic: Bullous pemphigoid (Ref), dermatitis (interstitial granulomatous) (Ref), erythema multiforme, Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Altered serum glucose, amenorrhea (Ref), change in libido, hypoglycemia (Ref), hyponatremia (Ref), thyroiditis (Ref)
Genitourinary: Anorgasmia (Ref), breast hypertrophy (Ref), ejaculation failure (Ref), ejaculatory disorder, urinary incontinence (Ref)
Hematologic & oncologic: Thrombocytopenia (Ref)
Hepatic: Hepatotoxicity (Ref), increased liver enzymes (Ref)
Hypersensitivity: Anaphylaxis, angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref), hypersensitivity angiitis (Ref)
Infection: Parasitic infection (Ref)
Nervous system: Agitation (Ref), coma (Ref), encephalopathy (Ref), movement disorder (Ref), myoclonus (facial) (Ref), polyneuropathy (Ref), stuttering (Ref), suicidal ideation (Ref), suicidal tendencies (Ref), visual hallucination (Ref)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, rhabdomyolysis (Ref)
Respiratory: Respiratory depression (Ref)
Hypersensitivity to gabapentin or any component of the formulation
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. A small case series demonstrates altered gabapentin exposure post-bariatric surgery (Wallerstedt 2021). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen. Gabapentin use reduced opioid requirements in bariatric surgery patients when included in a perioperative multimodal pain management regimen (Hung 2022; Tubog 2023).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition (Mehrizi 2012).
• Renal impairment: Use with caution in patients with renal impairment; dose adjustment required.
• Seizure disorder: The safety and efficacy of the ER formulation has not been studied in patients with epilepsy.
• Substance misuse: Use with caution in patients with a history of substance misuse, including alcohol, benzodiazepines, cannabis, cocaine, and opioids; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur (Evoy 2017; Mersfelder 2016).
Dosage form specific issues:
• Product interchangeability: IR and ER products are not interchangeable with each other or with gabapentin enacarbil due to differences in formulations, indications, and pharmacokinetics.
Other warnings/precautions:
• Tumorigenic potential: Male rat studies demonstrated an association with pancreatic adenocarcinoma (clinical implication in humans is unknown).
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency in patients with epilepsy or other withdrawal symptoms (eg, confusion, irritability, tachycardia, diaphoresis). Therapy should be withdrawn gradually over ≥1 week to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal (Norton 2001; Tran 2005).
Withdrawal has been described following abrupt discontinuation of gabapentin in infants; reported symptoms included episodic tachycardia, emesis, and irritability; symptoms resolved after gabapentin was restarted. Avoid abrupt discontinuation, especially in patients on prolonged therapy (use >1 week); it has been recommended that gabapentin be continued even if patients are made nothing by mouth (NPO) (Carrasco 2015; Edwards 2016; McPherson 2021).
Bradycardia has been reported in infants receiving gabapentin. A case series reported bradycardia occurred within 24 hours of initiation of gabapentin in former 26-week GA twins; the dose was lowered with resolution of bradycardia in one twin; the other twin had gabapentin discontinued without a trial of a lower dose (Edwards 2016). Another case series reported bradycardia in 3 infants; however, all infants were also receiving other medications known to increase risk of bradycardia; following a reduction in the gabapentin dose, bradycardia resolved (O'Mara 2018). Patients should be monitored closely.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Neurontin: 100 mg, 300 mg, 400 mg
Generic: 100 mg, 300 mg, 400 mg
Solution, Oral:
Neurontin: 250 mg/5 mL (470 mL [DSC])
Neurontin: 250 mg/5 mL (470 mL) [strawberry anise flavor]
Generic: 250 mg/5 mL (473 mL); 250 mg/5 mL (5 mL, 6 mL, 470 mL)
Tablet, Oral:
Gabarone: 100 mg, 400 mg [contains corn starch]
Neurontin: 600 mg, 800 mg [scored]
Generic: 600 mg, 800 mg
Tablet, Oral, Extended Release:
Gralise: 300 mg [contains soybean lecithin]
Gralise: 450 mg, 600 mg, 750 mg, 900 mg
Generic: 300 mg, 600 mg
Yes
Capsules (Gabapentin Oral)
100 mg (per each): $0.02 - $0.58
300 mg (per each): $0.03 - $1.34
400 mg (per each): $0.06 - $1.60
Capsules (Neurontin Oral)
100 mg (per each): $3.54
300 mg (per each): $8.86
400 mg (per each): $10.63
Solution (Gabapentin Oral)
250 mg/5 mL (per mL): $0.12 - $0.83
Solution (Neurontin Oral)
250 mg/5 mL (per mL): $1.25
Tablets (Gabapentin (Once-Daily) Oral)
300 mg (per each): $10.64 - $11.49
600 mg (per each): $10.64 - $11.49
Tablets (Gabapentin Oral)
600 mg (per each): $0.07 - $2.53
800 mg (per each): $0.10 - $3.05
Tablets (Gabarone Oral)
100 mg (per each): $20.00
400 mg (per each): $20.00
Tablets (Gralise Oral)
300 mg (per each): $12.77
450 mg (per each): $12.77
600 mg (per each): $12.77
750 mg (per each): $19.15
900 mg (per each): $19.15
Tablets (Neurontin Oral)
600 mg (per each): $16.83
800 mg (per each): $20.19
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Neurontin: 100 mg, 300 mg, 400 mg [contains corn starch, fd&c blue #2 (indigotine,indigo carmine)]
Generic: 100 mg, 300 mg, 400 mg
Tablet, Oral:
Neurontin: 600 mg, 800 mg [contains corn starch]
Generic: 600 mg, 800 mg
Note: Commercial oral solution is available (50 mg/mL).
A 100 mg/mL suspension may be made with immediate-release capsules and either a 1:1 mixture of Ora-Sweet (100 mL) and Ora-Plus (100 mL) or 1:1 mixture of methylcellulose 1% (100 mL) and Simple Syrup N.F. (100 mL). Grind the contents of sixty-seven 300 mg immediate-release capsules in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 200 mL. Label "shake well" and "refrigerate." Stable for 91 days refrigerated (preferred) or 56 days at room temperature.
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: May consider administration of first dose on first day at bedtime to avoid somnolence and dizziness. May be administered without regard to meals; administration with meals may decrease adverse GI effects. Dose may be administered as combination of dosage forms. When given 3 times daily, the maximum time between doses should not exceed 12 hours.
Capsule: Administer with plenty of water. Although the manufacturer recommends swallowing capsules whole, some centers have opened the capsules and mixed the contents in drinks (eg, orange juice) or food (eg, applesauce) when necessary (Ref).
Administration via feeding tube: Note: Absorption may be reduced if administered via jejunum; if jejunal administration is necessary, consider increased monitoring for efficacy (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes (≥8 French): Open capsule(s) and disperse contents in 10 to 30 mL purified water; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition during gabapentin administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Oral solution (commercially available): Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Administration via feeding tube: Note: Enteral feeding tube administration of gabapentin oral solution is not preferred due to its extremely high osmolality. If alternatives are not available and use of the oral solution is necessary for feeding tube administration, consider the risks versus benefits and ensure adequate volumes of purified water are utilized during administration (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes (≥8 French): Note: Absorption may be reduced if administered via jejunum; if jejunal administration is necessary, consider increased monitoring for efficacy (Ref).
Dilute dose in at least an equivalent volume of purified water immediately prior to administration to reduce osmolality (Ref); some experts recommend diluting in a volume of purified water that is at least 3 times the gabapentin solution volume (eg, 10 mL gabapentin solution diluted in at least 30 mL purified water) as this may help decrease the risk of adverse GI effects caused by high osmolality (Ref). Draw up diluted solution into enteral dosing syringe and administer via feeding tube.
Dosage form information: Some undiluted formulations have been reported to have osmolalities of ~6,300 to ~8,300 mOsm/kg (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during gabapentin administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablet, immediate release: The 600 mg and 800 mg tablets are scored and may be split if a half tablet is needed; manufacturer recommends that half tablets not used within 28 days of breaking the scored tablets should be discarded.
Administration via feeding tube: Note: Absorption may be reduced if administered via jejunum; if jejunal administration is necessary, consider increased monitoring for efficacy (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in 15 to 30 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated gabapentin tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed prior to administration (Ref).
General guidance: Hold enteral nutrition during gabapentin administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Oral:
Immediate release: May administer without regards to meals. Administer first dose on first day at bedtime to avoid somnolence and dizziness. Dosage must be adjusted for renal function; when given 3 times daily, the maximum time between doses should not exceed 12 hours. Capsules may be opened and sprinkled on food (eg, applesauce, orange juice, pudding) for patients unable to swallow capsules (Ref).
Extended release: Administer with evening meal. Swallow whole; do not chew, crush, or split.
Bariatric surgery: Gabapentin extended release slowly dissolves in the stomach for absorption in the small intestine. Bariatric surgery may significantly alter this release mechanism in an unknown manner; providers should determine if the condition being treated can be safely monitored or if a switch to an alternate formulation is necessary (Ref). Gabapentin is available in an immediate-release formulation. Oral solutions may contain nonabsorbable sugars (eg, mannitol, sorbitol, xylitol) that can cause dumping syndrome after bariatric surgery; refer to package labeling and monitor for tolerability with use (Ref).
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Absorption may be reduced if administered via jejunum; if jejunal administration is necessary, consider increased monitoring for efficacy (Ref).
Oral capsule:
Gastric (eg, NG, G-tube ) or post-pyloric (eg, J-tube) tubes (≥8 French): Open capsule(s) and disperse contents in 10 to 30 mL purified water; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
General guidance: Hold enteral nutrition (EN) during gabapentin administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral solution (commercially available):
Note: Enteral feeding tube administration of gabapentin oral solution is not preferred due to its extremely high osmolality. If alternatives are not available and use of the oral solution is necessary for feeding tube administration, consider the risks versus benefits and ensure adequate volumes of purified water are utilized during administration (Ref).
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes (≥8 French): Dilute dose in at least an equivalent volume of purified water immediately prior to administration to reduce osmolality (Ref); some experts recommend diluting in a volume of purified water that is at least 3 times the gabapentin solution volume (eg, 10 mL gabapentin solution diluted in at least 30 mL purified water) as this may help decrease the risk of adverse GI effects caused by high osmolality (Ref). Draw up diluted solution into enteral dosing syringe and administer via feeding tube.
Dosage form information: Some undiluted formulations have been reported to have osmolalities of ~6,300 to ~8,300 mOsm/kg (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition (EN) during gabapentin administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral tablet, immediate release:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes: Crush tablet(s) into a fine powder and disperse in 15 to 30 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated gabapentin tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold enteral nutrition (EN) during gabapentin administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral tablet, extended release: Enteral feeding tube administration utilizing gabapentin ER tablets is not recommended. Crushing modified release dosage forms (eg, ER tablets) may result in release of excessive doses, variable serum concentrations, and risk of severe adverse effects (Ref).
Not e: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Capsules and tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Use scored 600 or 800 mg tablets that are broken in half within 28 days of breaking the tablet.
Oral solution: Store refrigerated at 2°C to 8°C (36°F to 46°F).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Gralise: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022544s029lbl.pdf#page=21
Adjunct for treatment of partial seizures with or without secondary generalized seizures (Neurontin: FDA approved in ages ≥3 years and adults); management of post-herpetic neuralgia (Gralise, Neurontin: FDA approved in adults); has also been used as adjunct in the treatment of neuropathic pain, neonatal pain, and agitation.
Gabapentin may be confused with gabapentin enacarbil, gemfibrozil
Neurontin may be confused with Motrin, Neoral, nitrofurantoin, Noroxin [DSC], Zarontin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (GABA analog) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Long-Term Care Settings).
Gabapentin is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with recurrent falls or for the treatment of nonneuropathic pain (O’Mahony 2023).
Substrate of OCT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Aluminum Hydroxide: May decrease serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after administration of antacids containing aluminum hydroxide or magnesium hydroxide. Risk D: Consider Therapy Modification
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of Gabapentin. Cetirizine (Systemic) may decrease serum concentration of Gabapentin. Risk C: Monitor
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
LevETIRAcetam: May increase CNS depressant effects of Gabapentin. Risk C: Monitor
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Salts: May increase CNS depressant effects of Gabapentin. Specifically, high dose intravenous/epidural magnesium sulfate may enhance the CNS depressant effects of gabapentin. Magnesium Salts may decrease serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after use of a magnesium-containing antacid. Monitor patients closely for evidence of reduced response to gabapentin therapy. Monitor for CNS depression if high dose IV/epidural magnesium sulfate is used. Risk D: Consider Therapy Modification
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Tablet, solution (immediate release): No significant effect on rate or extent of absorption; extended release tablet: Increases rate and extent of absorption. Management: Administer immediate release products without regard to food. Administer extended release with food.
Extended release tablet should be taken with food.
Evaluate pregnancy status prior to use. Pregnancy testing is recommended before treating acute alcohol withdrawal symptoms; however, treatment should not be delayed in symptomatic patients if pregnancy status is unknown (ASAM 2020).
Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient’s reproductive lifespan (ACOG 2020; NICE 2022). Obtain reference serum trough concentrations of gabapentin twice prior to pregnancy while patient has stable seizure control and is on a minimal dose (Arfman 2020).
Gabapentin crosses the placenta (Ohman 2005; Ohman 2009).
Gabapentin monotherapy in pregnant patients with epilepsy is associated with lower risks of major congenital malformations compared to some other antiseizure medications (Battino 2024; Blotière 2019; Bromley 2023; Desrochers 2024; Pack 2024; Patorno 2020; Vajda 2023; Vajda 2024; Wang 2024). Data are insufficient to evaluate the risk of neurodevelopmental outcomes (IQ scores or autism spectrum disorder) in children following in utero exposure to gabapentin (Dreier 2023; Honybun 2024; Knight 2021; Pack 2024). Screen for major congenital malformations and monitor fetal growth when antiseizure medications are used during pregnancy. Conduct age-appropriate developmental screening in children who had in utero exposure to antiseizure medications (Pack 2024).
Adequate data are not available to determine if pregnancy-induced physiologic changes alter gabapentin pharmacokinetic properties in a clinically significant way (Arfman 2020; Tomson 2019). Monitor total serum trough concentrations of gabapentin during pregnancy and adjust doses based on decreasing concentrations and seizure control (Arfman 2020; Pack 2024). Formulate a plan to return to prepregnancy doses after delivery (NICE 2022).
Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).
Gabapentin is used off-label for the treatment of restless leg syndrome; however, current guidelines note there is insufficient evidence to recommend its use in pregnant patients for this indication. Avoid use of gabapentin for restless leg syndrome during pregnancy (IRLSSG/EURLSSG/RLS-F [Garcia-Borreguero 2016]; Picchietti 2015).
Pharmacological agents should not be used for the treatment of alcohol use disorder during pregnancy unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder; agents other than gabapentin may be preferred when treatment is needed (APA [Reus 2018]; ASAM 2020).
Gabapentin has been evaluated for the treatment of severe nausea and vomiting of pregnancy (Guttuso 2021), however agents other than gabapentin are currently recommended (ACOG 2018).
Data collection to monitor pregnancy outcomes following exposure to antiepileptic drugs is ongoing. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or www.aedpregnancyregistry.org).
Seizure frequency and duration; renal function; weight; behavior in children; signs and symptoms of suicidality (eg, anxiety, depression, behavior changes).
Routine monitoring of drug levels is not required; a specific target serum concentration range for antiseizure response has not been established (Lindberger 2003); a minimum effective serum concentration may be 2 mcg/mL (Krasowski 2010).
Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence degradation or uptake of GABA. High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit. This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception. These effects on restless leg syndrome are unknown.
Absorption: Variable, from proximal small bowel by L-amino transport system; saturable process; dose-dependent
Distribution: Vd: 58 ± 6 L; CSF concentrations are ~20% of plasma concentrations
Protein binding: <3%
Metabolism: Not metabolized
Bioavailability: Inversely proportional to dose due to saturable absorption:
Immediate release:
900 mg/day: 60%
1,200 mg/day: 47%
2,400 mg/day: 34%
3,600 mg/day: 33%
4,800 mg/day: 27%
Extended release: Variable; increased with higher fat content meal
Half-life elimination:
Infants 1 month to Children 12 years: 4.7 hours
Adults, normal: 5 to 7 hours; increased half-life with decreased renal function; anuric adult patients: 132 hours; adults during hemodialysis: 3.8 hours
Time to peak: Immediate release: Infants 1 month to Children 12 years: 2 to 3 hours; Adults: 2 to 4 hours; Extended release: 8 hours
Excretion: Proportional to renal function; urine (as unchanged drug)
Clearance: Apparent oral clearance is directly proportional to CrCl: Clearance in infants is highly variable; oral clearance (per kg) in children <5 years of age is higher than in children ≥5 years of age
Altered kidney function: Adults: In CrCl <30 mL/minute, half-life is approximately 52 hours (immediate release). In moderate and severe renal impairment, Cl was decreased to 3 and 1 L/hour, respectively, compared with 5 to 7 L/hour in nonrenal impairment patients (ER).
