Gabapentin
Clinical data | |
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Trade names | Neurontin, others[1] |
Other names | CI-945; GOE-3450; DM-1796 (Gralise) |
AHFS/Drugs.com | Monograph |
MedlinePlus | a694007 |
License data |
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Pregnancy category |
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Dependence liability | Low – Moderate |
Addiction liability | Low |
Routes of administration | By mouth |
Drug class | Gabapentinoid |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 27–60% (inversely proportional to dose; a high fat meal also increases bioavailability)[5][6] |
Protein binding | Less than 3%[5][6] |
Metabolism | Not significantly metabolized[5][6] |
Elimination half-life | 5 to 7 hours[5][6] |
Excretion | Kidney[5][6] |
Identifiers | |
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JSmol) | |
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Gabapentin, sold under the brand name Neurontin among others, is an
Gabapentin was first approved for use in 1993.
Medical uses
Gabapentin is recommended for use in
Seizures
Gabapentin is approved for the treatment of
Neuropathic pain
Gabapentin is recommended as a first-line treatment for chronic neuropathic pain by various medical authorities.[7][8][26][27] This is a general recommendation applicable to all neuropathic pain syndromes except for trigeminal neuralgia, where it may be used as a second- or third-line agent.[8][27]
In regard to the specific diagnoses, a systematic review has found evidence for gabapentin to provide pain relief for some patients with
Gabapentin shows substantial benefit (at least 50% pain relief or a patient global impression of change (PGIC) "very much improved") for neuropathic pain (postherpetic neuralgia or peripheral diabetic neuropathy) in 30–40% of subjects treated as compared to those treated with placebo.[9]
Evidence finds little or no benefit and significant risk in those with chronic low back pain or sciatica.[28][29] Gabapentin is not effective in HIV-associated sensory neuropathy[30] and neuropathic pain due to cancer.[31]
Anxiety
There is a small amount of research on the use of gabapentin for the treatment of anxiety disorders.[32][33]
Gabapentin is effective for the long-term treatment of social anxiety disorder and in reducing preoperative anxiety.[22][23]
In a controlled trial of breast cancer survivors with anxiety,[33] and in a trial for social phobia,[32] gabapentin significantly reduced anxiety levels.
For panic disorder, gabapentin has produced mixed results.[33][32][23]
Sleep
Gabapentin is effective in treating sleep disorders such as insomnia and restless legs syndrome that are the result of an underlying illness, but comes with some risk of discontinuation and withdrawal symptoms after prolonged use at higher doses.[34]
Gabapentin enhances slow-wave sleep in patients with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal.[35]
Drug dependence
Gabapentin is moderately effective in reducing the symptoms of
Gabapentin is ineffective in cocaine dependence and methamphetamine use,
Other
Gabapentin is recommended as a first-line treatment of the acquired pendular nystagmus, torsional nystagmus, and infantile nystagmus; however, it does not work in periodic alternating nystagmus.[44][45][46]
Gabapentin decreases the frequency of hot flashes in both menopausal women and patients with breast cancer. However, antidepressants have similar efficacy, and treatment with estrogen more effectively prevents hot flashes.[47]
Gabapentin reduces
Gabapentin does not appear to provide benefit for bipolar disorder,[23][37][56] complex regional pain syndrome,[57] post-surgical pain,[58] or tinnitus,[59] or prevent episodic migraine in adults.[60]
Contraindications
Gabapentin should be used carefully and at lower doses in people with
Side effects
Suicide
The gabapentin label contains a warning of an increased risk of suicidal thoughts and behaviors.[4] According to an insurance claims database study, gabapentin use is associated with about 40% increased risk of suicide, suicide attempt and violent death as compared with a reference anticonvulsant drug topiramate. The risk is increased for both bipolar disorder and epilepsy patients.[66] Another study has shown an approximately doubled rate of suicide attempts and self-harm in patients with bipolar disorder who are taking gabapentin versus those taking lithium.[67] A large Swedish study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences.[68]
Respiratory depression
Serious breathing suppression, potentially fatal, may occur when gabapentin is taken together with
Withdrawal and dependence
Withdrawal symptoms typically occur 1–2 days after abruptly stopping gabapentin (almost unambiguously due to extended use and during a very short-term rebound phenomenon) — similar to, albeit less intense than most benzodiazepines.[72] Agitation, confusion and disorientation are the most frequently reported, followed by gastrointestinal complaints and sweating, and more rare tremor, tachycardia, hypertension and insomnia.[72] In some cases, users experience withdrawal seizures after chronic or semi-chronic use in the absence of periodic cycles or breaks during repeating and consecutive use.[73] All these symptoms subside when gabapentin is re-instated[72] or tapered off gradually at an appropriate rate.[citation needed]
On its own, gabapentin appears to not have a substantial addictive power. In human and animal experiments, it shows limited to no
Overdose
Through excessive ingestion, accidental or otherwise, persons may experience overdose symptoms including drowsiness, sedation, blurred vision, slurred speech, somnolence, uncontrollable jerking motions, and anxiety. A very high amount taken is associated with breathing suppression, coma, and possibly death, particularly if combined with alcohol or opioids.[73][75]
Pharmacology
Pharmacodynamics
Gabapentin is a
The
Gabapentin is a potent activator of voltage-gated potassium channels
Despite the fact that gabapentin is a structural
Pharmacokinetics
Gabapentin is
The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule.[4][82] Drugs that increase the transit time of gabapentin in the small intestine can increase its oral bioavailability; when gabapentin was co-administered with oral morphine, the oral bioavailability of a 600 mg dose of gabapentin increased by 50%.[82]
Gabapentin at a low dose of 100 mg has a
Gabapentin can cross the
Gabapentin undergoes little or no metabolism.[77][82]
Gabapentin is generally safe in patients with liver cirrhosis.[87]
Gabapentin is
Chemistry
Gabapentin is a 3,3-di
Synthesis
A process for chemical synthesis and isolation of gabapentin with high yield and purity[94] starts with conversion of 1,1-cyclohexanediacetic anhydride to 1,1-cyclohexanediacetic acid monoamide and is followed by a 'Hofmann' rearrangement in an aqueous solution of sodium hypobromite prepared in situ.
History
Gabapentin was designed by researchers at
Society and culture
Legal status
United Kingdom
Effective April 2019, the United Kingdom reclassified the drug as a class C controlled substance.[101][102][103][104][105]
United States
Effective 1 July 2017, Kentucky classified gabapentin as a schedule V controlled substance statewide.[106] Effective 9 January 2019, Michigan also classified gabapentin as a schedule V controlled substance.[107] Gabapentin is scheduled V drug in other states such as West Virginia,[108] Tennessee,[109] Alabama,[110] and Virginia.[111] Gabapentin is not scheduled or considered a controlled substance (as per the Controlled Substances Act) at the federal level.
Off-label promotion
Although some small, non-controlled studies in the 1990s—mostly sponsored by gabapentin's manufacturer—suggested that treatment for bipolar disorder with gabapentin may be promising,[112] the preponderance of evidence suggests that it is not effective.[113]
Franklin v. Parke-Davis case
Subsequent to the corporate acquisition of the original patent holder, the pharmaceutical company Pfizer admitted that there had been violations of FDA guidelines regarding the promotion of unproven off-label uses for gabapentin in the Franklin v. Parke-Davis case (see below).
While off-label prescriptions are common for a number of drugs, marketing of off-label uses of a drug is not.
Reuters reported on 25 March 2010, that "Pfizer Inc violated federal racketeering law by improperly promoting the epilepsy drug Neurontin ... Under federal RICO law the penalty is automatically tripled, so the finding will cost Pfizer $141 million."[115] The case stems from a claim from Kaiser Foundation Health Plan Inc. that "it was misled into believing Neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions. Pfizer argued that Kaiser physicians still recommend the drug for those uses",[116] and that "the insurer's website also still lists Neurontin as a drug for neuropathic pain."[117] The Wall Street Journal noted that Pfizer spokesman Christopher Loder said, "We are disappointed with the verdict and will pursue post-trial motions and an appeal."[118] He later added that "the verdict and the judge's rulings are not consistent with the facts and the law."[115]
Gabasync
In November 2011, the results of a double-blind, placebo-controlled study (financed by Hythiam and carried out at
Usage trends
The period from 2008 to 2018 saw a significant increase in the consumption of gabapentinoids. A study published in Nature Communications in 2023, highlights this trend, demonstrating a notable escalation in sales of gabapentinoids. The study, which analyzed healthcare data across 65 countries/ regions, found that the consumption rate of gabapentinoids had doubled over the decade, driven by their use in wide range of indications.[130]
Brand names
Gabapentin was originally marketed under the brand name Neurontin. Since it became generic, it has been marketed worldwide using over 300 different brand names.
Related drugs
Parke-Davis developed a drug called pregabalin, which is related in structure to gabapentin, as a successor to gabapentin.[132] Another similar drug atagabalin has been unsuccessfully tried by Pfizer as a treatment for insomnia.[133] A prodrug form (gabapentin enacarbil)[134] was approved by the U.S. Food and Drug Administration (FDA).
Recreational use
Gabapentin when taken in excess, can induce euphoria, a sense of calm, a
After Kentucky's implementation of stricter legislation regarding opioid prescriptions in 2012, there was an increase in gabapentin-only and multi-drug use in 2012–2015. The majority of these cases were from overdose in suspected suicide attempts. These rates were also accompanied by increases in abuse and recreational use.[143]
Withdrawal symptoms, often resembling those of
Veterinary use
In cats, gabapentin can be used as an analgesic in multi-modal pain management,[145] anxiety medication to reduce stress in cats for travel or vet visits,[146] and anticonvulsant.[147] Veterinarians may prescribe gabapentin as an anticonvulsant and pain reliever in dogs. It is also used to treat chronic pain-associated nerve inflammation in horses and dogs. Side effects include tiredness and loss of coordination but they generally go away within 24 hours of starting the medication.[148][147]
References
- ^ a b "International listings for Gabapentin". Drugs.com. Archived from the original on 16 February 2016. Retrieved 9 February 2016.
- ^ "Gabapentin Use During Pregnancy". Drugs.com. 2 December 2019. Retrieved 21 December 2019.
- ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
- ^ a b c d e f g h i j k l "Neurontin- gabapentin capsule Neurontin- gabapentin tablet, film coated Neurontin- gabapentin solution". DailyMed. 11 April 2019. Retrieved 21 December 2019.
- ^ a b c d e "Neurontin, Gralise (gabapentin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 16 December 2014. Retrieved 6 April 2014.
- ^ S2CID 265753780.
- ^ a b c "1 Recommendations | Neuropathic pain in adults: pharmacological management in non-specialist settings | Guidance". NICE. 20 November 2013. Retrieved 14 December 2020.
- ^ S2CID 14236933.
- ^ PMID 28597471.
- ^ PMID 32521436.
- ^ PMID 23642658.
- ^ S2CID 216082872.
- ISBN 978-0-08-045702-4. Archivedfrom the original on 8 September 2017.
- ^ ISBN 978-1-4685-4410-7.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Gabapentin – Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- ^ S2CID 39262014.
- ^ Stempel J (2 June 2014). "Pfizer to pay $325 million in Neurontin settlement". Reuters. Retrieved 11 June 2018.
- ^ PMID 30480717.
- S2CID 85497732.
- ISBN 978-0-393-70857-8. Archivedfrom the original on 6 January 2016.
- ^ S2CID 252983016.
- ^ PMID 34819636.
- S2CID 46952737.
- S2CID 6943460.
- PMID 17372630.
- ^ PMID 25575710.
- PMID 28809936.
- PMID 29970367.
- PMID 21203440.
- PMID 29486015.
- ^ S2CID 38188832.
- ^ S2CID 4321472.
- ^ PMID 28769860.
- S2CID 4046961.
- PMID 24364635.
- ^ PMID 26835178.
- S2CID 201662179.
- PMID 31077485.
- ^ PMID 29241365.
- PMID 20081039.
- PMID 24250527.
- PMID 30687936.
- S2CID 21477128.
- S2CID 40370476.
- S2CID 1950738.
- S2CID 209462426.
- S2CID 25028259.
- S2CID 21669996.
- PMID 21767770.
- PMID 33283264.
- S2CID 39737885.
- PMID 24142589.
- PMID 22013182.
- S2CID 10662268.
- PMID 34577534.
- PMID 20054678.
- PMID 27535436. Archived from the originalon 29 September 2020. Retrieved 22 August 2020.
- PMID 21940981.
- PMID 23797675.
- PMID 25590213.
- S2CID 39571068.
- S2CID 32010921.
- S2CID 53165515.
- ^ "Side effects of gabapentin". National Health Service. 16 September 2021. Retrieved 20 January 2024.
- PMID 20388896.
- S2CID 54130760.
- PMID 31189556.
- ^ a b "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR)". U.S. Food and Drug Administration (FDA). 19 December 2019. Archived from the original on 22 December 2019. Retrieved 21 December 2019. This article incorporates text from this source, which is in the public domain.
- ^ "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) When used with CNS depressants or in patients with lung problems" (PDF). Food and Drug Administration. 19 December 2019. Archived from the original on 22 December 2019. Retrieved 22 December 2019. This article incorporates text from this source, which is in the public domain.
- S2CID 266985259.
- ^ S2CID 21108959.
- ^ S2CID 10345555.
- S2CID 49344251.
- ISBN 978-0-9626523-7-0.
- ^ PMID 16376147.
- ^ S2CID 33200190.
- ^ PMID 17222465.
- PMID 17403543.
- PMID 30021858.
- PMID 18656534.
- ^ S2CID 16398062.
- ^ PMID 23567998.
- ^ PMID 26305616.
- ^ S2CID 32513471.
- PMID 10518579.
- S2CID 264888110.
- PMID 20505847.
- ISBN 978-0-323-52998-3.
- ISBN 978-1-4511-5348-4.
- ISBN 978-0-323-17080-2.
- ^ ISBN 978-0-470-01552-0.
- PMID 21428817.
- ^ Kumar A, Soudagar SR, Nijasure AM, Panda NB, Gautam P, Thakur GR. "Process For Synthesis Of Gabapentin".
- ISBN 978-1-118-67846-6.
- ^ "Drug Profile: Gabapentin". Adis Insight.
- PMID 14664664. Archived from the original(PDF) on 17 September 2010. Retrieved 15 August 2006.
- PMID 23342236.
- ^ Orrange S (31 May 2013). "Yabba Dabba Gabapentin: Are Gralise and Horizant Worth the Cost?". GoodRx, Inc. Archived from the original on 23 June 2018. Retrieved 22 June 2018.
- ^ "Gabapentin controlled release – Depomed". Adis Insight.
- ^ "Pregabalin and gabapentin will become controlled drugs in April". NursingNotes. 17 October 2018. Archived from the original on 16 June 2019. Retrieved 16 June 2019.
- ^ "Re: Pregabalin and Gabapentin advice" (PDF). GOV.UK. 14 January 2016.
- ^ "Pregabalin and gabapentin: proposal to schedule under the Misuse of Drugs Regulations 2001". GOV.UK. 10 November 2017. Retrieved 2 April 2020.
- S2CID 53520780.
- ^ "Pregabalin and gabapentin to be controlled as Class C drugs". GOV.UK. 15 October 2018. Retrieved 2 April 2020.
- ^ "Important Notice: Gabapentin Becomes a Schedule 5 Controlled Substance in Kentucky" (PDF). Kentucky State Board of Pharmacy. March 2017. Retrieved 18 June 2018.
- ^ "Gabapentin Scheduled as Controlled Substance to help with State's Opioid Epidemic". Retrieved 16 April 2019.
- ^ "WV Code 212". www.wvlegislature.gov. Retrieved 30 May 2020.
- ^ "Gabapentin will be a Schedule V controlled substance in Tennessee effective July 1, 2018" (PDF). tn.gov. Retrieved 30 May 2020.
- ^ "Pharmacy Division". Alabama Department of Public Health (ADPH). Retrieved 30 May 2020.
- ^ "Scheduling of Gabapentin" (PDF). Virginia Department of Health Professions. Retrieved 28 June 2023.
- S2CID 17085492.
- PMID 22575611.
- ^ Tansey B (14 May 2004). "Huge penalty in drug fraud, Pfizer settles felony case in Neurontin off-label promotion". San Francisco Chronicle. p. C-1. Archived from the original on 23 June 2006.
- ^ a b Berkrot B (25 March 2010). "US jury's Neurontin ruling to cost Pfizer $141 mln". Reuters. Archived from the original on 19 October 2015.
- ^ "Pfizer faces $142M in damages for drug fraud". Bloomberg Businessweek. 25 March 2010. Archived from the original on 19 October 2015. Retrieved 13 January 2012.
- ^ Van Voris B, Lawrence J (26 March 2010). "Pfizer Told to Pay $142.1 Million for Neurontin Marketing Fraud". Bloomberg News. Archived from the original on 13 May 2013. Retrieved 13 January 2012.
- ^ Kamp J (25 March 2010). "Jury Rules Against Pfizer in Marketing Case". The Wall Street Journal. Archived from the original on 19 October 2015. Retrieved 13 January 2012.
- ^ a b c Pelley S, ed. (7 December 2007). "Prescription For Addiction". 60 Minutes. CBS News.
- ^ "Prometa Founder's Spotty Background Explored". 3 November 2006. Archived from the original on 23 September 2015.
- ^ "United States V. Terren S. Peizer". www.justice.gov. 1 March 2023.
- .
- PMID 22082089.
- ^ a b Alpert B (7 November 2005). "Curb Your Cravings For This Stock". The Wall Street Journal.
- ^ Schuster H, Peterson R (7 December 2007). "Prescription For Addiction". CBS News.
- ^ Kari Huus (5 February 2007). "Unproven meth, cocaine 'remedy' hits market". NBC News.
- ^ Humphreys K (24 January 2012). "The Rise and Fall of a "Miracle Cure" for Drug Addiction". Washington Monthly.
- ^ Ramshaw E (20 January 2008). "Texas' Prometa program for treating meth addicts draws skeptics". Dallas Morning News. Archived from the original on 27 October 2010.
- ^ Feuerstein A (13 November 2007). "Hythiam, Shire, Genentech; Talk is proving cheap at Hythiam". Biotech Notebook. TheStreet.
- PMID 37591833.
- ^ "Gralise Approval History". Drugs.com.
- PMID 16425669.
- S2CID 22241527.
- PMID 19787095.
- PMID 22867659.
- S2CID 8959463. Archived from the original(PDF) on 2 March 2019.
- S2CID 195878855.
- ISBN 978-0-19-936057-4.
- PMID 28767350.
- S2CID 24396685.
- PMID 29179227.
- S2CID 208537638.
- S2CID 59226292.
- PMID 27265421.
- PMID 21831060.
- S2CID 7780988.
- ^ a b "Gabapentin". Plumb's Veterinary Drugs. Retrieved 2 April 2021.
- ^ Coile C. "Gabapentin for Dogs: Uses and Side Effects". American Kennel Club. Archived from the original on 6 December 2022. Retrieved 12 May 2023.