Gabapentin in the Treatment of Peripheral neuropathy

Gabator300/400 mg capsule

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Introduction to Neuropathy

Neuropathic pain develops as a result of damage or dysfunction of the nerves of the Peripheral or Central nervous system.

Common examples include painful diabetic neuropathy, post-herpetic neuralgia and trigeminal neuralgia

NICE clinical guideline 96, Neuropathic pain :The pharmacological management of neuropathic pain in adults in non-specialist settings Issue date: March 2010 2

Classification of Neuropathic Pain

Neurophathies may also be categorized based on a functional classification (motor, sensory, autonomic, or mixed) or the type of onset (acute - hours or days, subacute - weeks or months, or chronic - months or years). 

The most common form of neuropathy is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs on both sides of the body.

http://www.medicalnewstoday.com/articles/147963.php 3

Causes of Neuropathic Pain

Neuropathic Pain

Exposure to drugs, alcohol, toxins

Traumatic Nerve injury/ compression

Viral infection

Vascular related neurodegenerative

Nutritional deficiency

Cancer related (disease or treatment

Metabolic disturbance

Surgical procedures/ Amputation

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Nociceptive vs Neuropathic Pain

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Pain Pathways in CNS

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Brain

Prevalence Of Neuropathy in Eastern Cape. South Africa (2011)

South Afr J Anaesth Analg 2011;17(5), 329-337

• Neuropathy is a common general complaint in community• There is a need for focused attention on women and the elderly.

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Taylor BK, Curr Pain Headache Rep; 2001;5;151-161

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Pharmacologic Treatment for Neuropathic pain

CATEGORY EXAMPLES

Topical Agents Lidocaine patch 5%, capsaicin

Opioids Oxycodone, Tramadol, Fentanyl, Morphine, Hydrocodone

Antidepressants

Tricyclic Antidepressants Amitryptiline, Nortryptiline, Desipramine, Imipramine, Doxepin

Selective Noredrinaline reuptake inhibitors

Duloxetine, Venlafaxine

Anticonvulsants Carbamazepine, Valproate, Lamotrigine, Topiramate, Gabapentin, Pregabalin

9http://www.medscape.org/viewarticle/530441_1http://www.medscape.org/viewarticle/530441_1

GABATOR

Class: Antiepileptic Mechanism of action

– Gabapentin binds to alpha – 2 – delta subunit of voltage-sensitive calcium channels and decreases the release of glutamate and Substance-P neurotransmitters

– Gabapentin enters the body through a carrier protein mechanism.

Glutamate & substance P

GABAPENTIN

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Approved Indication

Gabapentin is used primarily for the treatment of seizures, neuropathic pain

FDA approval– Neuropathic pain associated with postherpetic neuralgia– Adjunctive therapy for partial seizures

Adult Adolescent (12 Years & Above) Pediatric (3-12 years)

http://www.rxlist.com/neurontin-drug/indications-dosage.htm

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Guidelines & Recommendations

1. Adopted from: http://www.aan.com/professionals/practice/pdfs/pn_guideline_physicians.pdf2. Adopted from http://www.aan.com/practice/guideline/uploads/480.pdf3. Eur J Neurol. 2010 Sep;17(9):1113-e88.4. Pain Res Manag. 2007 Spring; 12(1): 13–21.5. J Int Med Res. 2010 Mar-Apr;38(2):295-317.6. Epilepsia. 2006 Jul;47(7):1094-120.

Pharmacokinetics

Absorption– Bioavailability: 60%, Increased with high fat meal– Peak plasma time: 2-4 hr

Distribution– Protein Binding: less than 3%

Metabolism– Not metabolized

Excretion– Kidney: 76% to 81%– Feces: 10% to 23%– Half-life: 5-7 hr

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Indication and Dosage

Partial seizure; Adjunct– Start with 300 mg 3 times daily - 900 to 1800 mg given in 3

divided doses, dosages up to 2400 mg have been well tolerated

Post-herpetic neuralgia– 300 mg/day – 1800 mg/day

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Dosing: Special Population

Dosage in Renal Failure

Dosage in Hepatic Insufficiency– No dose adjustment is required

Dosage in Geriatric Patients– Because elderly patients are more likely to have decreased renal

function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients

SEVERITY

RENAL FUNCTION

CREATININE CLEARANCE 

(ML/MIN)

TOTAL DAILY DOSE RANGE

(MG/DAY)DOSE REGIMEN (MG)

MILD > 30-59 400-1400 200 BID 300 BID 400 BID 500 BID 700 BID

MODERATE > 15-29 200-700 200 QD 300 QD 400 QD 500 QD 700 QD

SEVERE 15 100-300 100 QD 125 QD 150QD 200 QD 300 QD

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Adverse Reactions & Contraindications

Adverse reaction

– Fatigue– Weight Increase– Back Pain – Peripheral Edema– Dizziness– Somnolence– Nausea– Chills & Fever

Contraindication

– If known hypersensitivity to the product or any of its components

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Drug Interactions

Drug Interaction Comments

Antacid  Reduced the bioavailability of gabapentin

Gabapentin be taken at least 2 hours following Antacid administration

Naproxen Coadministration of naproxen sodium capsules with Gabapentin appears to increase the amount of gabapentin absorbed by 12% to 15%. 

Hydrocodone Coadministration of Gabapentin decreases hydrocodone Cmax and AUC values in a dose-dependent manner relative to administration of hydrocodone alone

Hydrocodone increases gabapentin AUC values by 14%

Cimetidine The mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance fell by 10% in presence of cimetidine

Cimetidine appeared to alter the renal excretion of gabapentin 

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Gabapentin in Neuropathy

Neurol J Southeast Asia 2002; 7 : 25 – 34

Gabapentin showed significant reduction in pain and other related symptoms in all types of neuropathic pain

p<0.5N = 1156

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Gabapentin on QoL

Gabapentin improves overall quality of life (QoL) in patients with neuropathic pain

Pain. 2002 Oct;99(3):557-66.

2020

Place in Therapy

Salient Features

• Effective in spectrum of neuropathic pain

• Improves various aspects of Neuropathic pain

• Improves co-morbid conditions associated with pain

• Improves overall quality of life

• No significant drug interactions

• Recommended & approved by various regulatory bodies

• An effective choice in employed patients

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