Gabapentin (Lexi-Drugs)

Pronunciation
         

(GA ba pen tin)

Brand Names: US

Gralise; Gralise Starter; Neurontin

Brand Names: Canada

ACT Gabapentin [DSC]; AG-Gabapentin; APO-Gabapentin; Auro-Gabapentin; BCI Gabapentin [DSC]; BIO-Gabapentin; DOM-Gabapentin; GD-Gabapentin; GLN-Gabapentin; JAMP-Gabapentin; Mar-Gabapentin; MYLAN-Gabapentin [DSC]; Neurontin; PHL-Gabapentin [DSC]; PMS-Gabapentin; Priva-Gabapentin; PRO-Gabapentin; RAN-Gabapentin; RIVA-Gabapentin; TARO-Gabapentin; TEVA-Gabapentin; VAN-Gabapentin

Pharmacologic Category

Anticonvulsant, MiscellaneousGABA Analog

Dosing: Adult

Alcohol use disorder, moderate to severe (alternative agent) (off-label use): 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 (Brower 2008; Mason 2014; VA/DoD 2015). Note: Gabapentin is suggested by some experts as an alternative when first-line agents cannot be used (Johnson 2018; VA/DoD 2015). Gabapentin may be misused by some patients with substance use disorders; evaluate for risk and signs of addiction and dependence (Mersfelder 2016).

Alcohol withdrawal, mild (alternative agent) (off-label use): Note: Withdrawal will progress at different rates in some patients; flexibility in dosing and duration is warranted (Holt 2018; VA/DoD 2015). The following is one suggested regimen based on a single randomized, double-blind trial: 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 (Myrick 2009).

Cough, chronic refractory (alternative agent) (off-label use): Immediate release: Oral: Initial: 300 mg once daily; increase dose gradually based on response and tolerability in increments of 300 mg to a maximum dose of 900 mg twice daily (ACCP [Gibson 2016]; Ryan 2012). Re-evaluate therapeutic need after 6 months (ACCP [Gibson 2016]).

Fibromyalgia (alternative agent) (off-label use): Note: For patients who do not respond to or tolerate preferred agents (Goldenberg 2018): Immediate release: Oral: Initial: 100 to 300 mg once daily at bedtime; increase dose gradually based on response and tolerability every 1 to 2 weeks to a target dose of 1.2 to 2.4 g/day in divided doses (Arnold 2007; Goldenberg 2018).

Hiccups (singultus) (off-label use): Immediate release: Oral: Usual dose range: 300 mg to 1.2 g/day in 3 to 4 divided doses (Hernández 2004; Jatzko 2007; Moretti 2004; Porzio 2010; Schuchmann 2007). Can be discontinued the day after hiccups subside; long-term therapy may be warranted for persistent or relapsing hiccups (eg, palliative care) (Lembo 2018). Note: In patients with refractory hiccups, may use in combination with a proton pump inhibitor, baclofen, or metoclopramide (Kohse 2017).

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 (Bone 2002; Rosenquist 2018). For critically ill patients with neuropathic pain, gabapentin may be a useful component of multimodal pain control (SCCM [Devlin 2018]).

Immediate release: Oral: Initial: 100 to 300 mg 1 to 3 times daily (ADA [Pop-Busui 2017]; Dolgun 2014; Mishra 2012); increase dose based on response and tolerability to a target dose range of 300 mg to 1.2 g 3 times daily (AAN [Bril 2011]; ADA [Pop-Busui 2017]; EFNS [Attal 2010]; IASP [Finnerup 2015])

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 (IASP [Finnerup 2015]; Sandercock 2012)

Postherpetic neuralgia:

Immediate release: Oral: 300 mg once on day 1, 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.

Postoperative pain (off-label use): Immediate release: Oral: 300 mg to 1.2 g as a single dose, given 1 to 2 hours prior to surgery or immediately following surgery as part of a multimodal analgesia regimen (Chou 2016; Doleman 2015; Peng 2007; Yu 2013). Note: Some experts avoid use in patients with sleep-disordered breathing (eg, obstructive sleep apnea) (Joshi 2018; Mariano 2018).

Pruritus, chronic (alternative agent) (off-label use): Note: For patients with pruritus resistant to preferred therapies (Matsuda 2016; Weisshaar 2012):

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 (Kanitakis 2006; Winhoven 2004; Yilmaz 2010). Higher doses up to 3.6 g/day have been used in oncology populations (Demierre 2006; Lee 2010).

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 (Gunal 2004; Kobrin 2018; Nofal 2016; Razeghi 2009).

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 (range: 300 mg to 2.4 g/day). 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 (Garcia-Borreguero 2002; Happe 2003; IRLSSG/EURLSSG/RLS-F [Garcia-Borreguero 2016]; Saletu 2010; Silber 2018; Vignatelli 2006).

Seizures, focal (partial) onset: Immediate release: Oral: Initial: 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. Some experts recommend a lower starting dose (eg, 100 mg 3 times daily) with titration as tolerated (Schachter 2018).

Social anxiety disorder (alternative agent) (off-label use): Note: Monotherapy or adjunctive therapy for patients who do not tolerate or respond to preferred agents (Stein 2018): 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 (Pande 1999).

Vasomotor symptoms associated with menopause (off-label use):

Immediate release: Oral: Initial: 300 to 400 mg once daily at bedtime; some experts use an initial dose of 100 mg once daily to avoid adverse effects (Santen 2018); 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 (ACOG 2014; NAMS 2015; Reddy 2006; Toulis 2009). Some experts suggest gabapentin for women whose symptoms occur primarily at night and favor a maximum dose of 900 mg to 1.2 g, given as one dose at bedtime (ES [Stuenkel 2015]; Santen 2018).

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 (Pinkerton 2014)

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) (Norton 2001; Tran 2005).

Dosing: Geriatric

Restless legs syndrome (off-label use): Immediate release: Oral: Initial: 100 mg once daily (IRLSSG/EURLSSG/RLS-F [Garcia-Borreguero 2016])

Other indications: Refer to adult dosing. For postoperative pain (off-label use), some experts avoid use in patients >65 years of age (Joshi 2018).

Discontinuation of therapy: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Note: Estimation of renal function for dosing adjustments should be done using the Cockcroft-Gault formula.

Immediate release:

CrCl ≥60 mL/minute: Oral: 300 mg to 1.2 g 3 times daily

CrCl >30 to 59 mL/minute: Oral: 200 to 700 mg twice daily

CrCl >15 to 29 mL/minute: Oral: 200 to 700 mg once daily

CrCl 15 mL/minute: Oral: 100 to 300 mg once daily

CrCl <15 mL/minute: Oral: Reduce daily dose in proportion to creatinine clearance based on dose for creatinine clearance of 15 mL/minute (eg, reduce dose by one-half [range: 50 to 150 mg/day] for CrCl 7.5 mL/minute)

ESRD requiring hemodialysis: Oral: Dose based on CrCl plus a single supplemental dose of 125 to 350 mg (given after each 4 hours of hemodialysis) or in patients with uremic pruritus (off-label use), give 100 to 300 mg only after dialysis on hemodialysis days (Gunal 2004; Kobrin 2018; Nofal 2016; Razeghi 2009).

Extended release: Note: Follow initial dose titration schedule if treatment naive.

CrCl ≥60 mL/minute: Oral: 1.8 g once daily

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.

ESRD requiring hemodialysis: Use is not recommended.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, gabapentin is not hepatically metabolized.

Dosing: Pediatric

Note: Do not exceed 12 hours between doses with 3 times daily dosing. Pediatric doses presented as mg/kg/day and mg/kg/dose; use precaution.

Seizures, partial onset; adjunctive therapy: Oral: Immediate release: Note: If gabapentin is discontinued or if another anticonvulsant is added to therapy, it should be done slowly over a minimum of 1 week.

Children 3 to <12 years:

Initial: 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: 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: 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: 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: Oral: Immediate release: Children and Adolescents: Initial: 5 mg/kg/dose up to 300 mg at bedtime; day 2: Increase to 5 mg/kg/dose twice daily (up to 300 mg twice daily); day 3: Increase to 5 mg/kg/dose 3 times daily (up to 300 mg 3 times daily); further titrate with dosage increases (not frequency) to effect; American Pain Society (APS) recommends a lower initial dose of 2 mg/kg/day which may be considered if concurrent analgesics are also sedating; usual dosage range: 8 to 35 mg/kg/day divided into 3 doses daily (APS, 2008; Galloway, 2000); maximum daily dose: 3,600 mg/day

Dosing: Renal Impairment: Pediatric

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.

Gabapentin Dosing Adjustments in Renal Impairment

Creatinine Clearance

(mL/min)

Total Daily Dose Range

(mg/day)

Dosage Regimens

(Maintenance Doses)

(mg)

ACrCl <15 mL/minute: Reduce daily dose in proportion to creatinine clearance.

BSupplemental 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

900 to 3,600

300

3 times/day

400

3 times/day

600

3 times/day

800

3 times/day

1,200

3 times/day

>30 to 59

400 to 1,400

200 twice daily

300 twice daily

400 twice daily

500 twice daily

700 twice daily

>15 to 29

200 to 700

200 daily

300 daily

400 daily

500 daily

700 daily

15A

100 to 300

100 daily

125 daily

150 daily

200 daily

300 daily

HemodialysisB

Posthemodialysis Supplemental Dose

125 mg

150 mg

200 mg

250 mg

350 mg

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, adjustment not necessary since gabapentin is not hepatically metabolized.

Use: Labeled Indications

Postherpetic neuralgia: Management of postherpetic neuralgia (PHN) in adults.

Seizures, focal (partial) onset (immediate release only): As adjunctive therapy in the treatment of focal (partial) seizures with and without secondary generalization in adults and pediatric patients 3 years of age and older with epilepsy.

Use: Off-Label: Adult
  Alcohol use disorder, moderate to severe (alternative agent)Level of Evidence [B, G]

Data from randomized, double-blind, placebo-controlled studies support the use of gabapentin in the maintenance of abstinence in patients with alcohol use disorder Ref.

Based on the American Psychiatric Association (APA) guidelines for the pharmacological treatment of patients with alcohol use disorder, gabapentin is suggested for patients with alcohol use disorder (moderate to severe) who want to decrease or abstain from use of alcohol and either prefer gabapentin or are unable to tolerate or are unresponsive to naltrexone and acamprosate Ref. Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for moderate to severe alcohol use disorder is effective and suggested when first-line pharmacotherapy is contraindicated or ineffective Ref.

  Alcohol withdrawal, mild (alternative agent)Level of Evidence [B, G]

Data from a randomized, double-blind, active-controlled study support the use of gabapentin in the treatment of alcohol withdrawal Ref.

Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for mild alcohol withdrawal is effective and suggested when the risk of benzodiazepines outweigh the benefits (eg, inadequate monitoring available, abuse liability, contraindication, adverse reaction) Ref.

  Cough, chronic refractory (alternative agent)Level of Evidence [C, G]

Data from a small, randomized, double-blind, placebo-controlled trial showed that gabapentin significantly improves cough-specific quality of life in patients with refractory chronic cough compared to placebo. Participants with central sensitization of the cough reflex exhibited a greater response to gabapentin treatment compared to participants without central sensitization Ref.

Based on the American College of Chest Physicians (ACCP) guidelines for the treatment of unexplained chronic cough, gabapentin, on a therapeutic trial basis, is suggested in patients with unexplained chronic cough as long as the potential side effects and risk-benefit profile are discussed prior to use, and there is reassessment at 6 months prior to continuation of treatment Ref.

  Fibromyalgia (alternative agent)Level of Evidence [B]

Data from a randomized, double-blind, placebo-controlled study support the use of gabapentin in the treatment of pain and sleep disturbances associated with fibromyalgia RefAccess Full Off-Label Monograph

  Hiccups (singultus)Level of Evidence [C]

Data from a limited number of patients in case reports/series and a retrospective chart review suggest that gabapentin (monotherapy or as an adjunct to other agents such as baclofen, cisapride, omeprazole, haloperidol, and metoclopramide) may decrease the frequency and severity of persistent or intractable hiccups RefAccess Full Off-Label Monograph

  Neuropathic pain (other than postherpetic neuralgia)Level of Evidence [A, G]

In a meta-analysis of trials evaluating the treatment of neuropathic pain, including painful polyneuropathy and spinal cord injury pain, gabapentin was shown to be safe and effective Ref. Data from meta-analyses support the use of immediate-release gabapentin for reducing pain by more than 50% in diabetic neuropathy Ref. Data from a limited number of clinical trials support the use of extended-release gabapentin in reducing pain by more than 50% and improving sleep in diabetic neuropathy Ref.

Based on guidelines from the International Association for the Study of Pain (IASP), European Federation of Neurological Societies (EFNS), and Society of Critical Care Medicine (SCCM), gabapentin is effective and recommended for the management of peripheral neuropathy Ref. Based on guidelines from the EFNS, IASP, and National Institute for Health and Care Excellence (NICE), gabapentin is effective and recommended as first-line therapy, supported by strong evidence, in the management of diabetic neuropathy Ref. The IASP guidelines recommend both immediate- and extended-release gabapentin Ref. In contrast, a guideline from the American Academy of Neurology (AAN), American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation states that gabapentin is probably effective and should be considered an alternative treatment for painful diabetic neuropathy based on limited benefit in 2 controlled trials Ref. Similarly, a position statement from the American Diabetes Association (ADA) recommends gabapentin as a second-line option RefAccess Full Off-Label Monograph

  Postoperative painLevel of Evidence [B, G]

Data from 3 meta-analyses support the use of preemptive doses of gabapentin to decrease postoperative pain and opioid use Ref.

Based on the American Pain Society, American Society of Regional Anesthesia and Pain Medicine, and American Society of Anesthesiologists guidelines on the management of postoperative pain, gabapentin should be considered as part of a perioperative multimodal analgesia regimen.

  Pruritus, chronic (neuropathic or malignancy related) (alternative agent)Level of Evidence [C, G]

Data from a limited number of patients studied suggest that gabapentin may be beneficial for the treatment of chronic pruritus, including brachioradial pruritus Ref.

Based on European Dermatology Forum (EDF) and European Academy of Dermatology and Venerology (EADV) guidelines for the treatment of chronic pruritus, gabapentin is recommended for chronic pruritus of neuropathic origin. Evidence for brachioradial pruritus in based on anecdotal (case report) data Ref.

  Pruritus, uremicLevel of Evidence [B, G]

Data from randomized, blinded, controlled trials and a meta-analysis support the use of gabapentin in the treatment of uremic pruritus unresponsive to previous therapy Ref.

Based on European Dermatology Forum (EDF) and European Academy of Dermatology and Venerology (EADV) guidelines for the treatment of chronic pruritus, gabapentin is recommended for chronic kidney disease-associated pruritus RefAccess Full Off-Label Monograph

  Restless legs syndromeLevel of Evidence [B, G]

Gabapentin in the management of restless legs syndrome (RLS) has been evaluated in small controlled trials, demonstrating benefits compared with placebo. Gabapentin enacarbil is FDA-approved for the treatment of RLS Ref.

The American Academy of Sleep Medicine (AASM) guidelines regarding RLS management consider gabapentin effective based on low-level evidence and note that patients with pain symptoms appeared to benefit most. The benefit-risk ratio is unclear. The European Federation of Neurological Societies/European Neurological Society/European Sleep Research Society (EFNS/ENS/ESRS) Task Force guidelines consider gabapentin effective for short-term management and possibly effective for long-term management of RLS. Additional study is needed to establish optimal dosing. Based on the International Restless Legs Syndrome Study Group, European Restless Legs Syndrome Study Group, and RLS Foundation (IRLSSG/EURLSSG/RLS-F) guidelines for the prevention and treatment of dopaminergic augmentation in restless legs syndrome, α2δ ligands (eg, gabapentin) are effective and should be considered for the initial treatment of patients with RLS due to their minimal risk of augmentation. Additionally, patients who experience augmentation on dopaminergic agents may benefit from a switch to α2δ ligands (eg, gabapentin). However, the guidelines note that long-term studies are needed. Access Full Off-Label Monograph

  Social anxiety disorder, adjunct to antidepressants or monotherapy (alternative agent)Level of Evidence [C]

Data from a limited number of patients studied in a double-blind, placebo-controlled trial suggest that gabapentin may be beneficial for the treatment of social anxiety disorder Ref.

  Vasomotor symptoms associated with menopauseLevel of Evidence [B, G]

Data from meta-analyses and an individual patient pooled analysis support the use of immediate-release gabapentin for decreasing the frequency and severity of hot flashes in postmenopausal women and breast cancer survivors Ref. Data from a randomized, double-blind, placebo-controlled study support the use of extended-release gabapentin for decreasing frequency and severity of hot flashes and associated sleep interference in postmenopausal women Ref.

Based on the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) position statement on menopause, the Endocrine Society (ES) guideline on treatment of symptoms of menopause, and the North American Menopause Society (NAMS) position statement on nonhormonal management of menopause-associated vasomotor symptoms, gabapentin is an effective and recommended alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy. Based on the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) breast cancer survivorship care guideline, gabapentin may be used to help mitigate vasomotor symptoms of premature menopause in women previously treated for breast cancer. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Alcohol Use Disorder:

American Psychiatric Association (APA), “Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder,” January 2018

Bipolar Disorder:

CANMAT/ISBD, “2018 Guidelines for the Management of Patients With Bipolar Disorder,” March 2018

Chronic Cough:

ACCP, “Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report,” 2016

Critical Care:

ACCM/SCCM, “Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the Intensive Care Unit,” September 2018

Diabetic Neuropathy:

American Academy of NeurologyAmerican Association of Neuromuscular and Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, “Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy,” April 2011

American Diabetes Association, “Diabetic Neuropathy: A Position Statement by the American Diabetes Association,” 2017

European Federation of Neurological Societies (EFNS), “EFNS guidelines on the pharmacological treatment of neuropathic pain, 2010 revision,” 2010

International Association for the Study of Pain,” Pharmacotherapy for neuropathic pain in adults: Systematic review, meta-analysis and updated NeuPSIG recommendations,” 2015

National Institute for Health and Care Excellence, “Neuropathic pain in adults: Pharmacological management in non-specialist settings,” 2013

Menopause:

Committee on the Evolution of Oncology Practice (CEPO), “Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations,” 2013

Endocrine Society, “Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline,” 2015

North American Menopause Society (NAMS), Nonhormonal management of menopause-associated vasomotor symptoms, 2015

Postoperative pain:

American Pain Society, the American Society of Regional Anesthesia and the American Society of Anesthesiologists, “Guidelines on the management of postoperative pain,” February 2016

Restless Legs Syndrome (RLS):

American Academy of Sleep Medicine, “The treatment of restless legs syndrome and periodic limb movement disorder in adults – An update for 2012: Practice parameters with an evidence-based systematic review and meta-analysis,” 2012

European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society, “European guidelines on management of restless legs syndrome: Report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society,” November 2012

International Restless Legs Syndrome Study Group (IRLSSG), European Restless Legs Syndrome Study Group (ERLSSG), and Restless Legs Syndrome Foundation, “Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: A combined task force of the IRLSSG, ERLSSG and the RLS Foundation,” May 2016

Seizure Disorders:

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy,” 2018

Administration: 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.

Extended release: Administer with evening meal. Swallow whole; do not chew, crush, or split.

Administration: Pediatric

Immediate release: Capsule, tablet, oral solution: 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; do not administer within 2 hours of magnesium- or aluminum-containing antacids. When given 3 times daily, the maximum time between doses should not exceed 12 hours. Capsule should be administered with plenty of water to ensure complete swallowing. 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 (Gidal 1998; Khurana 1996). 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.

Dietary Considerations

Extended release tablet should be taken with food.

Storage/Stability

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).

Extemporaneously Prepared

Note: Commercial oral solution is available (50 mg/mL)

A 100 mg/mL suspension may be made with tablets (immediate release) 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). Crush sixty-seven 300 mg tablets 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.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, vomiting, diarrhea, or dry mouth. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), swollen glands, memory impairment, vision changes, confusion, tremors, shortness of breath, excessive weight gain, swelling of arms or legs, severe loss of strength and energy, involuntary eye movements, twitching, seizures, bruising, bleeding, chills, pharyngitis, muscle pain, muscle weakness, abnormal movements, difficulty swallowing, change in balance, difficulty speaking, difficulty focusing, severe dizziness, passing out, agitation, irritability, panic attacks, or mood changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Neurontin: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM229208.pdf

Gralise: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM245196.pdf

Contraindications

Hypersensitivity to gabapentin or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/angioedema: May occur after the first dose or at any time during treatment. Discontinue therapy and seek immediate medical care if signs or symptoms of anaphylaxis or angioedema occur.

• CNS depression: May cause CNS depression including somnolence and dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Multiorgan hypersensitivity: Potentially serious, sometimes fatal multiorgan hypersensitivity (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) has been reported with some antiepileptic drugs, including gabapentin. Monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, cardiac, and/or hematologic systems; fever, rash, and eosinophilia may also be present. Discontinue immediately if suspected.

• Neuropsychiatric effects: Use in pediatric patients with epilepsy has been associated with the occurrence of CNS adverse effects of mild to moderate intensity. The most significant include emotional lability, hostility (eg, aggressive behaviors), changes in behavior and thinking (eg, concentration problems and changes in school performance), and hyperkinesia (primarily restlessness and hyperactivity).

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dose adjustment required.

• Seizure disorder: The safety and efficacy of the extended release formulation has not been studied in patients with epilepsy.

• Substance abuse: Use with caution in patients with a history of substance abuse, including alcohol, benzodiazepines, cannabis, cocaine, and opioids; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur (Evoy 2017; Mersfelder 2016).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Product interchangeability: Immediate release and extended release 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: Anticonvulsants 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).

Geriatric Considerations

Studies in the elderly have shown a decrease in clearance as age increases. This is most likely due to age-related decreases in renal function. Since many elderly have a CrCl <60 mL/minute, dose reductions may be needed. Renal function estimates and dosage adjustments for gabapentin in older adults should be done using the Cockcroft-Gault equation; data has shown that estimation using the modification of diet in renal disease (MDRD-4) equation results in higher than recommended doses (Hellden 2013). Some practitioners may choose to start at a lower dose (100 mg/day) for patients with multiple risk factors for falls (eg, advanced age, postural hypotension, difficulties with gait and balance).

Warnings: Additional Pediatric Considerations

Neuropsychiatric adverse events, such as emotional lability (eg, behavioral problems), hostility, aggressive behaviors, thought disorders (eg, problems with concentration and school performance), and hyperkinesia (eg, hyperactivity and restlessness), have been reported in clinical trials of pediatric patients ages 3 to 12 years. Most of these pediatric neuropsychiatric adverse events are mild to moderate in terms of intensity but discontinuation of gabapentin may be required; children with mental retardation and attention-deficit disorders may be at increased risk for behavioral side effects (Lee 1996).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Gabapentin crosses the placenta. In a small study (n=6), the umbilical/maternal plasma concentration ratio was ~1.74. Neonatal concentrations declined quickly after delivery and at 24 hours of life were ~27% of the cord blood concentrations at birth (gabapentin neonatal half-life ~14 hours) (Ohman 2005). Pregnancy registry outcome data following maternal use of gabapentin during pregnancy is limited (Holmes 2012). Folic acid supplementation is recommended prior to and during pregnancy in women using gabapentin (Borgelt 2016; Picchietti 2015).

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 women for this indication (Picchietti 2015). Pharmacological agents should not be used for the treatment of alcohol use disorder in pregnant women unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder.

Patients exposed to gabapentin during pregnancy are encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Breast-Feeding Considerations

Gabapentin is present in breast milk.

The relative infant dose (RID) of gabapentin is 8.7% to 13% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 10 to 15 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).

The RID of gabapentin was calculated using a milk concentration of 8.7 mcg/mL, providing an estimated daily infant dose via breast milk of 1.3 mg/kg/day. This milk concentration was obtained following maternal administration of oral gabapentin 2,100 mg/day. Gabapentin was detected in the serum of two breastfeeding infants 2 to 3 weeks after delivery and in one infant after 3 months of breastfeeding. Adverse events were not reported in the breastfed infants (Ohman 2005).

Manufacturer recommendations may vary; the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Based on limited information, gabapentin is considered relatively compatible with breastfeeding; infants should be monitored for drowsiness, adequate weight gain, and developmental milestones (Davanzo 2013; Veiby 2015). Available guidelines state gabapentin may be considered for the treatment of refractory restless leg syndrome in breastfeeding women (Picchietti 2015). Pharmacological agents should not be used for the treatment of alcohol use disorder in breastfeeding women unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder (APA [Reus 2018]).

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Central nervous system: Dizziness (immediate release, adolescents and adults: 17% to 28%; extended release, adults: 11%; immediate release, children: 3%), drowsiness (immediate release, adolescents and adults: 19% to 21%; immediate release, children: 8%; extended release, adults: 5%), ataxia (immediate release, adolescents and adults: 1% to 13%), fatigue (immediate release, adolescents and adults: 11%; immediate release, children: 3%)

Infection: Viral infection (immediate release, children: 11%)

1% to 10%:

Cardiovascular: Peripheral edema (adolescents and adults: 2% to 8%), hypertension (extended release, adults: >1%), increased blood pressure (extended release, adults: >1%), vasodilatation (immediate release, adolescents and adults: 1%)

Central nervous system: Hostility (immediate release: 5% to 8%), emotional lability (immediate release: 4% to 6%), abnormality in thinking (immediate release: 2% to 3%), abnormal gait (immediate release, adults: 2%), amnesia (immediate release, adolescents and adults: 2%), depression (immediate release, adolescents and adults: 2%), status epilepticus (immediate release, adolescents and adults: 2%), confusion (extended release, adults: >1%), memory impairment (extended release, adults: >1%), lethargy (extended release, adults: 1%), pain (extended release, adults: 1%), vertigo (extended release, adults: 1%)

Dermatologic: Skin rash (extended release, adults: >1%), excoriation (immediate release, adolescents and adults: 1%)

Endocrine & metabolic: Weight gain (2% to 3%), hyperglycemia (immediate release, adults: 1%)

Gastrointestinal: Nausea (immediate release: ≤8%; extended release, adults: >1%), vomiting (immediate release: ≤8%), diarrhea (immediate release, adults: 6%), xerostomia (adolescents and adults: ≤5%;), constipation (adolescents and adults: 1% to 4%), dental disease (immediate release, adolescents and adults: 2%), dyspepsia (adolescents and adults: 1% to 2%), viral gastroenteritis (extended release, adults: >1)

Genitourinary: Impotence (immediate release, adolescents and adults: 2%), urinary tract infection (extended release, adults: 2%)

Hypersensitivity: Seasonal allergy (extended release, adults: >1%)

Infection: Infection (immediate release, adults: 5%), herpes zoster infection (extended release, adults: >1%)

Neuromuscular & skeletal: Tremor (immediate release, adolescents and adults: 7%), asthenia (immediate release, adults: 6%), hyperkinesia (immediate release: 3% to 5%), back pain (adolescents and adults: 2%), dysarthria (immediate release, adolescents and adults: 2%), limb pain (extended release, adults: 2%), joint swelling (extended release, adults: >1%)

Ophthalmic: Nystagmus (immediate release, adolescents and adults: 8%), diplopia (immediate release, adolescents and adults: 1% to 6%), amblyopia (immediate release: 3% to 4%), conjunctivitis (immediate release, adults: 1%)

Otic: Otitis media (immediate release, adults: 1%)

Respiratory: Bronchitis (immediate release, children: 3%), nasopharyngitis (extended release, adults: 3%), respiratory tract infection (immediate release, children: 3%), pharyngitis (immediate release, adolescents and adults: 1% to 3%), cough (immediate release, adolescents and adults: 2%), dry throat (immediate release, adolescents and adults: ≤2%), pneumonia (extended release, adults: >1%), upper respiratory tract infection (extended release, adults: >1%)

Miscellaneous: Fever (immediate release, children: 10%; extended release, adults: >1%), accidental injury (immediate release, adults: 3%)

<1%, postmarketing, and/or case reports: Agitation, altered serum glucose, anaphylaxis, angioedema, anorgasmia, breast hypertrophy, change in libido, DRESS syndrome, ejaculatory disorder, erythema multiforme, hyponatremia, increased creatine phosphokinase, increased liver enzymes, jaundice, movement disorder, rhabdomyolysis, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

None known.

Drug Interactions 

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Aluminum Hydroxide: May decrease the 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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Salts: May enhance the CNS depressant effect of Gabapentin. Specifically, high dose intravenous/epidural magnesium sulfate may enhance the CNS depressant effects of gabapentin. Magnesium Salts may decrease the 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 diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Morphine (Systemic): Gabapentin may enhance the CNS depressant effect of Morphine (Systemic). Morphine (Systemic) may increase the serum concentration of Gabapentin. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Orlistat: May decrease the serum concentration of Anticonvulsants. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect 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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect 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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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

Food Interactions

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.

Test Interactions

False positives have been reported with the Ames N-Multistix SG® dipstick test for urine protein

Monitoring Parameters

Periodic renal function, suicidality (eg, suicidal thoughts, depression, behavioral changes)

Advanced Practitioners Physical Assessment/Monitoring

Obtain periodic renal function tests; dosage adjustment may be needed. Assess for signs of depression, suicidal ideation, or behavioral changes. Ensure to prescribe correct dosage form; products are not interchangeable. Assess therapeutic response (seizure activity, force, type, duration) at beginning of therapy and periodically throughout; ensure dosing compliance. Assess for multiorgan hypersensitivity.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor therapeutic response (seizure activity, force, type, duration) at beginning of therapy and periodically throughout. Monitor for CNS depression and suicidal ideation and educate patient to report. Monitor for multiorgan sensitivity (lymphatic, hepatic, renal, cardiac, hematologic symptoms, fever, rash, eosinophilia). If treating seizures, observe and teach seizure/safety precautions. Educate patient on risk for daytime drowsiness with use.

Dosage Forms Considerations

Gralise is the extended release formulation.

Fanatrex FusePaq is a compounding kit for the preparation of an oral suspension. Refer to manufacturer’s labeling for compounding instructions.

Neuraptine cream is compounded from a kit. Refer to manufacturer’s labeling for compounding instructions.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Neurontin: 100 mg, 300 mg, 400 mg

Generic: 100 mg, 300 mg, 400 mg

Miscellaneous, Oral:

Gralise Starter: 300 & 600 mg (78 ea) [contains soybean lecithin]

Solution, Oral:

Neurontin: 250 mg/5 mL (470 mL) [strawberry anise flavor]

Generic: 250 mg/5 mL (470 mL, 473 mL); 300 mg/6 mL (6 mL); 250 mg/5 mL (5 mL, 470 mL)

Tablet, Oral:

Gralise: 300 mg [contains soybean lecithin]

Gralise: 600 mg

Neurontin: 600 mg, 800 mg [scored]

Generic: 600 mg, 800 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Neurontin: 100 mg, 300 mg, 400 mg

Generic: 100 mg, 300 mg, 400 mg

Tablet, Oral:

Neurontin: 600 mg, 800 mg

Generic: 600 mg, 800 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N03AX12
Generic Available (US)

May be product dependent

Pricing: US

Capsules (Gabapentin Oral)

100 mg (per each): $0.03 – $0.55

300 mg (per each): $0.04 – $7.48

400 mg (per each): $0.05 – $1.60

Capsules (Neurontin Oral)

100 mg (per each): $2.68

300 mg (per each): $6.70

400 mg (per each): $8.03

Misc (Gralise Starter Oral)

300 & 600 mg (per each): $10.18

Solution (Gabapentin Oral)

250 mg/5 mL (per mL): $0.32 – $0.83

Solution (Neurontin Oral)

250 mg/5 mL (per mL): $1.01

Tablets (Gabapentin Oral)

600 mg (per each): $0.33 – $3.16

800 mg (per each): $0.39 – $3.36

Tablets (Gralise Oral)

300 mg (per each): $11.19

600 mg (per each): $11.19

Tablets (Neurontin Oral)

600 mg (per each): $12.72

800 mg (per each): $15.26

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.

Mechanism of Action

Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis 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.

Pharmacodynamics/Kinetics

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

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: 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).

Dental Use

Neuropathic pain (consult with physician)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), dry throat, and dental abnormalities.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Pain (off-label use): Children >12 years and Adults: Oral: 300-1800 mg/day given in 3 divided doses has been the most common dosage range

Postherpetic neuralgia or neuropathic pain: Adults: Oral: Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day, daily doses >1800 mg do not generally show greater benefit)

FDA Approval Date
December 30, 1993
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Brand Names: International

Alpentin (ID); Anatin (LK); Bapex (MX); Barontin (KR); Bineurox (VN); Blugat (MX); Calmpent (PH); Carbatin (TW); Conventin (EG); Die Li (CN); Dineurin (CL); Dineurol (PY); Engaba (PK); Epiven (ID, PH); Epleptin (ZA); Etoclon (CR, DO, GT, HN, NI, PA, SV); G-Pentin (TH); Gabadin (PY); Gabagamma (LV, UA); Gabalept (RO, UA); Gabamax (BD); Gabanet (JO, LB, QA); Gabantin (MX, UA); Gabapen (JP); Gabapenin (KR); Gabaran (AU); Gabaron (PH); Gabasant (ID); Gabatin (CH, KR, LK); Gabator (PH, TZ, ZW); Gabatrex (BH, QA); Gabavex (PH); Gabenil (HK); Gabictal (CR, DO, GT, HN, NI, PA, SV); Gabin (IE); Gabix (PH); Gabon (BD); Gabutin (TH); Gantin (AU); Gapatin (TW); Gapridol (MX); Gaptin (EG); Gaty (TW); Gonnaz (PH); Gordius (LV); Mirgy (VN); Nepatic (ID); Nepsy (BD); Neuleptol (KR); Neupentin (LK); Neuran (HK, MY); Neuril (DK); Neurontin (AE, AR, AT, AU, BB, BE, BG, BH, BO, BR, CH, CN, CO, CY, CZ, DE, EC, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IN, IQ, IR, IS, IT, JO, KE, KR, KW, LB, LT, LU, LV, LY, MT, MX, MY, NL, NO, NZ, OM, PE, PH, PL, PR, PT, QA, RU, SA, SE, SG, SI, SK, SY, TH, TR, TW, UY, VE, YE, ZA); Neuropen (BD); Neuroplex (BH); Neurostil (IE); New-GABA (KR); Nopatic (MX); Nupentin (AU, NZ, SG); Nurona (JO, LB); Opipentin (ID); Pendine (AU); Pengatine (KR); Penral (LK); Pentalipsy (EG); Reinin (PH); Remaltin (TW); Rontin (TH); Sipentin (ID); Tebantin (UA, VN); Volar (JO, LB); Vultin (HK, TH); Vultin 600 (TH)

Gabapentin (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(GA ba pen tin)

Brand Names: US

Gralise; Gralise Starter; Neurontin

Brand Names: Canada

Neurontin

What is this drug used for?
  • It is used to treat seizures.
  • It is used to treat painful nerve diseases.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to gabapentin or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have kidney disease or are on dialysis.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • This drug is not the same as gabapentin enacarbil (Horizant™). Do not use in its place. Talk with the doctor.
  • A very bad and sometimes deadly reaction has happened with this drug. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
  • Memory problems or loss.
  • Change in eyesight.
  • Feeling confused.
  • Shakiness.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Feeling very tired or weak.
  • Not able to control eye movements.
  • If seizures are worse or not the same after starting this drug.
  • Any unexplained bruising or bleeding.
  • Swollen gland.
  • Fever or chills.
  • Sore throat.
  • Muscle pain or weakness.
  • Not able to focus.
  • Very bad dizziness or passing out.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Upset stomach or throwing up.
  • Diarrhea.
  • Dry mouth.
  • Feeling tired or weak.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.
  • If you are taking an antacid that has aluminum or magnesium in it, take this drug at least 2 hours after taking the antacid.
  • Gralise:
  • Take with the evening meal.
  • Swallow whole. Do not chew, break, or crush.
  • All other products:
  • Take with or without food. Take with food if it causes an upset stomach.
  • Capsules:
  • Swallow whole with a full glass of water.
  • Tablets:
  • You may break the tablet in half. Do not chew or crush.
  • If you break the tablet in half, use the other half of the tablet for the next dose, as told by the doctor. Throw away half-tablets not used within 28 days.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Liquid (solution):
  • Store in a refrigerator. Do not freeze.
  • All other products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • All dose forms:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Gabapentin (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(GA ba pen tin)

Brand Names: US

Gralise; Gralise Starter; Neurontin

Brand Names: Canada

Neurontin

What is this drug used for?
  • It is used to treat seizures.
  • It may be given to your child for other reasons. Talk with the doctor.
  • Gralise:
  • If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has kidney disease or is on dialysis.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • This drug is not the same as gabapentin enacarbil (Horizant™). Do not use in its place. Talk with the doctor.
  • A very bad and sometimes deadly reaction has happened with this drug. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Use with care in children. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
  • Memory problems or loss.
  • Change in eyesight.
  • Shakiness.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Not able to control eye movements.
  • Any unexplained bruising or bleeding.
  • Swollen gland.
  • Fever or chills.
  • Sore throat.
  • Muscle pain or weakness.
  • Not able to focus.
  • If seizures are worse or not the same after starting this drug.
  • Feeling confused.
  • Feeling very tired or weak.
  • Very bad dizziness or passing out.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Upset stomach or throwing up.
  • Diarrhea.
  • Dry mouth.
  • Feeling tired or weak.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • To gain the most benefit, do not miss giving your child doses.
  • If your child is taking an antacid that has aluminum or magnesium in it, give this drug at least 2 hours after your child takes the antacid.
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Capsules:
  • Have your child swallow whole with a full glass of water.
  • Tablets:
  • You may break the tablet in half. Do not let your child chew or crush.
  • If you break the tablet in half, use the other half of the tablet for the next dose, as told by the doctor. Throw away half-tablets not used within 28 days.
  • Liquid:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Liquid:
  • Store in a refrigerator. Do not freeze.
  • All other products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.