1. Gabapentin in the Treatment of Peripheral neuropathy
Gabator
300/400 mg capsule

2. 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
Peripheral Neuropathic Pain
Nerves of peripheral nervous system are damaged
Central Neuropathic pain
Nerves of Central nervous system are damaged
NICE clinical guideline 96, Neuropathic pain :The pharmacological management of neuropathic pain in adults in non-specialist settings Issue date: March

3. Classification of Neuropathic Pain
Mononeuropathy
Involvement of a single nerve
Multiple mononeuropathy
Two or more nerves individually affected.
Polyneuropathy
Generalized involvement of peripheral nerves
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.

4. Causes of Neuropathic Pain
Exposure to drugs, alcohol, toxins
Neuropathic Pain
Surgical procedures/ Amputation
Traumatic Nerve injury/ compression
Metabolic disturbance
Viral infection
Neuropathic pain is a disease, like myocardial infarction is a disease. Myocardial infarction may be caused by smoking, or hypertension, or diabetes. Multiple different things contribute to the cause of myocardial infarction, but myocardial infarction is the disease. Similarly, neuropathic pain is a disease, and this slide shows many of the different conditions that can result in neuropathic pain. But the pain is nonprotective. It is something that persists and behaves separately as a disease itself.
Cancer related (disease or treatment
Vascular related neurodegenerative
Nutritional deficiency

5. Nociceptive vs Neuropathic Pain

6. Pain Pathways in CNS
Brain

7. Prevalence Of Neuropathy in Eastern Cape. South Africa (2011)
Neuropathy is a common general complaint in community
There is a need for focused attention on women and the elderly.
South Afr J Anaesth Analg 2011;17(5),

8. Targets for controlling Neuropathic pain
Restore inhibitory neurotransmission: GABA
Block peripheral sensitization: Sodium channel
Block central sensitization
Modulate calcium channels
Taylor BK, Curr Pain Headache Rep; 2001;5;

9. 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

10. Glutamate & substance P
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

11. 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)

12. Guidelines & Recommendations
Level A drug In the treatment of PHN
Level B drug In the treatment of DPNP
American Academy of Neurology1,2
Level A drug
In trigeminal neuralgia, chronic radiculopathy
European Federation Neurological Societies Task Force3
First line treatment option
In management of chronic neuropathic pain
Canadian Pain Society4
First-line treatment
In peripheral neuropathic pain
Expert panel recommendations for the middle East region5
Elderly adults with partial-onset seizures
ILAE treatment guidelines6
Adopted from:
Adopted from
Eur J Neurol Sep;17(9):1113-e88.
Pain Res Manag Spring; 12(1): 13–21.
J Int Med Res Mar-Apr;38(2):
Epilepsia Jul;47(7):

13. 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

14. Indication and Dosage Partial seizure; Adjunct
Start with 300 mg 3 times daily 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

15. 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
200 BID
300 BID
400 BID
500 BID
700 BID
MODERATE
> 15-29
200 QD
300 QD
400 QD
500 QD
700 QD
SEVERE 15
100 QD
125 QD
150QD

16. Adverse Reactions & Contraindications
Fatigue
Weight Increase
Back Pain
Peripheral Edema
Dizziness
Somnolence
Nausea
Chills & Fever
If known hypersensitivity to the product or any of its components

17. 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 

18. Gabapentin in Neuropathy
Safety, tolerability, and efficacy of gabapentin in
neuropathic pain: Results of a post-marketing
surveillance study in 1214 Filipino patients
Ester S BITANGA MD, *Alejandro C BAROQUE MD, **Alberto S SANTOSOCAMPO
MD, **Almar Y GUEVARRA RN, **Margaret B QUERIJERO MD,
***Carlos L CHUA MD
Philippine Neurological Association, *Santo Tomas University Hospital, **Medical Affairs Division,
Pfizer Philippine, ***University of Philippine-Philippine General Hospital
Abstract
A post-marketing surveillance study of gabapentin usage in Filipino patients with neuropathic pain was
conducted. Safety, tolerability and analgesic efficacy were assessed after a minimum of two weeks of
gabapentin treatment, with starting and final doses determined by the prescribing physician. Of the
1,214 patients who entered the study, 95.7% completed the minimum two weeks duration of therapy.
The mean age was 54 years, and the most common neuropathic pain diagnoses were painful diabetic
neuropathy (30.4%), nonspecific neuropathies (20.2%), trigeminal neuralgia (12.8%), central pain after
stroke (8.8%), and post-herpetic neuralgia (8.4%). Ninety-two percent of patients were maintained
within a dose range of 300mg/day to 1200mg/day. The incidence of adverse events was 6%, and
consisted mostly of somnolence and dizziness, with 76% of patients reporting “very good” to
“excellent” tolerability. There were 34 documented dropouts (2.9%), of which only seven (0.6%) were
thought to be related to an adverse event from gabapentin. Visual analog scale pain scores declined
significantly from a mean of mm at baseline, to mm after treatment (p< 0.05). In
conclusion, gabapentin at 300mg/d to 1200mg/d is well tolerated and efficacious among Filipino
patients with various neuropathic pain syndromes.
Gabapentin showed significant reduction in pain and other related symptoms in all types of neuropathic pain
Neurol J Southeast Asia 2002; 7 : 25 – 34

19. Gabapentin on QoL
Pain Oct;99(3):
Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial.
Serpell MG; Neuropathic pain study group.
Source
University Department of Anaesthesia and Pain Management, Gartnavel General Hospital, 30 Shelly Court, G12 0YN, Scotland, Glasgow, UK.
Abstract
A double-blind, randomised, placebo-controlled 8-week study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain, using doses up to 2400 mg/day. The study used a novel design that was symptom- rather than syndrome-based; an approach that aimed to reflect the realities of clinical practice. Participants had a wide range of neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. Patients were randomised to gabapentin (n=153) or placebo (n=152). Gabapentin was given in three divided doses, initially titrated to 900 mg/day over 3 days, followed by two further increases, to a maximum of 2400 mg/day if required by the end of week 5. The primary outcome measure was changed in average daily pain diary score (baseline versus final week). Over the 8 week study, this score decreased (i.e. improved) by 1.5 (21%) in gabapentin treated patients and by 1.0 (14%) in placebo treated patients (P=0.048, rank-based analysis of covariance). Significant differences were shown in favour of gabapentin (P<0.05) for the Clinician and Patient Global Impression of Change, and some domains of the Short Form-McGill Pain Questionnaire. Improvements were also shown in patient-reported outcomes in quality of life, as seen by significant differences in favour of gabapentin in several domains of the Short-Form-36 Health Survey. Gabapentin was well tolerated and the majority of patients completed the study (79 versus 73% for placebo). The most common adverse events were mild to moderate dizziness and somnolence, most of which were transient and occurred during the titration phase. This study shows that gabapentin reduces pain and improves some quality-of-life measures in patients with a wide range of neuropathic pain syndromes.
Comment in
Gabapentin improves overall quality of life (QoL) in patients with neuropathic pain
Pain Oct;99(3):

20. Place in Therapy Gabapentin Broad spectrum of action Improves QoL
Over all symptom control
No Drug interactions
Benign side effect profile

21. 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

22. Thank You