2/12/2016

Updated Management of Painful

Diabetic Neuropathy:
Focus on Pregabalin
DR. dr. Yuanita Langi, SpPD-KEMD FINASIM

Diabetes is a progressive disease

Type 2 diabetes (T2DM) progression is characterised by decline in

beta-cell function and worsening insulin resistance1
Getting to, or maintaining, target HbA1c levels in T2DM requires
intensified treatment over time2

1. Fonseca VA. Br J Diab Vasc Dis 2008;8:S3

2. Nathan DM, et al. Diabetes Care 2009;32:193-203

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Top 10 Countries in Asia With the Highest Number of Persons With Type 2
Diabetes and Impaired Glucose Tolerance in the Age Group 20 to 79 Years in 2007
and Projected Data in 2025a

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long-term

Chronic complications

Complications of diabetes
Acute:
KAD
HONK
Hypoglycemia

Chronic:
Macrovascular
Cardiovascular disease
Cerebrovascular disease
Peripheral arterial disease
Microvascular
Diabetic retinopathy
Diabetic nephropathy
Neuropathy
(autonomic and peripheral)

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Diabetic Neuropathy

Diabetic Neuropathy
About 60-70% of people with diabetes
have mild to severe forms of nervous
system damage, including:
Impaired sensation or pain in the feet or
hands
Slowed digestion of food in the stomach
Carpal tunnel syndrome
Other nerve problems

More than 60% of nontraumatic lowerlimb amputations in the United States

occur among people with diabetes

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Risk Factors of Diabetic Neuropathy

Glucose control
Duration of diabetes
Damage to blood vessels
Mechanical injury to nerves
Autoimmune factors
Genetic susceptibility
Lifestyle factors
Smoking
Diet

Pathogenesis of Diabetic
Neuropathy
Metabolic factors
High blood glucose
Advanced glycation end products
Sorbitol
Abnormal blood fat levels

Ischemia
Impaired nerve fiber repair mechanisms

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Classification of Diabetic Neuropathy

Symmetric polyneuropathy
Autonomic neuropathy
Polyradiculopathy
Mononeuropathy

Symmetric Polyneuropathy
Most common form of diabetic neuropathy
Stocking-glove sensory loss
Symptoms/signs: pain, paresthesia/dysesthesia,
loss of vibratory sensation
Complications: callus, ulcers, charcot arthropathy,
dislocation and stress fractures
Treatment: Glucose control, pain control,
tricyclic antidepressants, topical creams,
anticonvulsants, foot care

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Autonomic Neuropathy
Affects the autonomic nerves controlling
internal organs
Peripheral
Genitourinary
Gastrointestinal
Cardiovascular

Is classified as clinical or subclinical based on

the presence or absence of symptoms

Polyradiculopathy
Lumbar polyradiculopathy (diabetic amyotrophy)
Thigh pain followed by muscle weakness and atrophy
Thoracic polyradiculopathy
Severe pain on one or both sides of the abdomen, possibly
in a band-like pattern
Diabetic neuropathic cachexia
Polyradiculopathy + peripheral neuropathy
Associated with weight loss and depression

Diagnosed by electromyographic (EMG) studies

Treatment
Foot care
Glucose control
Pain control

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Mononeuropathy
Peripheral mononeuropathy
Single nerve damage due to compression or
ischemia
Occurs in wrist (carpal tunnel syndrome), elbow,
or foot (unilateral foot drop)
Symptoms/Signs

numbness
edema
pain
prickling

Recommendations for the screening and treatment of

neuropathy in patients with diabetes

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Recommendations for the screening and

treatment neuropathy in patients with diabetes

PAIN
An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage or described
in terms of such damage
nociceptive
neuropathic

PAIN

acute
chronic

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Nociceptive vs Neuropathic Pain

Nociceptive
Pain

Mixed Type

Caused by activity in
neural pathways in
response to potentially
tissue-damaging stimuli

Caused by a
combination of both
primary injury and
secondary effects

Neuropathic
Pain
Initiated or caused by
primary lesion or
dysfunction in the nervous
system
CRPS*

Postoperative
pain

Arthritis

Mechanical
low back pain

Sickle cell
crisis

Sports/exercise
injuries

Postherpetic
neuralgia

Trigeminal
neuralgia

Neuropathic
low back pain

Central poststroke pain

Distal
polyneuropathy
(eg, diabetic, HIV)
*Complex regional pain syndrome
National Initiative on Pain Control, 2005

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AAN Guideline, 2011

PREGABALIN: mechanism of action

Pregabaline binds to the
subunit
alpha 2-delta voltagegated calcium channels
Modulate calcium
influx in
Hyperexecited
neurons and reduce
neurotransmitter
release (Substance P,
Calcitonin Gene-related
peptide, glutamate)

http://synapse.koreamed.org/DOIx.php?id=10.7599/hmr.2011.31.2.55&vmode=PUBREADE
R

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PREGABALIN vs GABAPENTIN

Anesth Analg
2007;105:180515

PREGABALIN
IN NEUROPATHIC PAIN GUIDELINE

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Pregabalin direkomendasikan sebagai terapi (Level A)

untuk nyeri neuropati
Nyeri Neuropati

AAN

FDA

IASP

EFNS

ICSI

Neuropati diabetik perifer

Neuralgia pasca herpes

Sindrom Fibromialgia

Nyeri neuropati kronis

Nyeri neuropati sentral

Post-Spinal Cord Injury

CPS

Keterangan:
AAN: American Academy of Neurology (2011)
FDA: US Food and Drug Administration (2007, 2012)
IASP: International Association for the Study of Pain (2010)
EFNS: European Federation of Neurological Societies (2010)
ICSI: Institute for Clinical Symptoms Improvement (2008)
CPS: Canadian Pain Society (2012)

Attal et al. 2010.7

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Time to onset of clinically

meaningful pain relief was
statistically significantly more
rapid with pregabalin groups
than placebo

The proportions of patients

experiencing 50 or 30%
reductions in pain levels
(responders) were
significantly greater in the
pregabalin groups than in
the placebo group and
were dose related.

Treatment with pregabalin across its effective dosing range is associated with significant, doserelated improvement in pain in patients with DPN

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Pain 115 (2005) 254263

Pain 115 (2005) 254263

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Pregabalin significantly reduce mean

pain score in neuropathic patients

Pain 115 (2005) 254263

Pregabalin significantly improve

mean pain-related sleep
disturbance

Pain 115 (2005) 254263

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BMC Family Practice 2010, 11:85

Pregabalin significantly reduce mean pain

score in neuropathic patients

BMC Family Practice 2010, 11:85

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Pregabalin significantly improve mean pain-related sleep

disturbance
BMC Family Practice 2010, 11:85

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Pregabalin is effective in treating

FM and is relatively safe.

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Opioid consumption during the first 24 h after surgery was significantly

reduced by pregabalin pregabalin had an opioid-sparing effect

The incidence of postoperative vomiting was significantly lower with the use of
pregabalin. This might be related to
the decreased use of opioids after surgery and the consequent decrease in
opioid-related adverse effects.

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Reduction of CPSP:
Gabapentin
Moderate-to-large
Pregabalin
Very large

Anesth Analg 2012;115:42842

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WHY COPY PRODUCTS EXIST?

Original products loose its patent protection

Copy Products have more opportunities

Health Care Cost is continue to increase, needs medicines
with lower price, especially for chronic disease.
Stringent GMP and BIOEQUIVALENCY requirements
ensure the Quality of the products, compare to its
originator

BIOEQUIVALENCE OF

BIOEKUIVALEN = THERAPEUTIC EQUIVALEN

Aaroon S Kesselheim, JAMA 2008;300(21) 2514-2526

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Bioequivalance Study of 150 mg Pregabalin (LEPTICA) CapsuleS Produced

by PT Dexa Medica in Comparson with the Comparator Product (LYRICA
CAPSULE 150 mg, Pfizer Manufacturing Deutscland GMBH, GermanyY)

LEPTICA Capsule 150 mg

Originator Capsule 150 mg

LEPTICA BIOEKUIVALEN

dengan originator

Originator

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Conclusion
60-70% of people with diabetes have mild to severe forms
complications of Diabetic Peripheral Neuropathic Pain.
Management of Diabetic Peripheral Neuropathic Pain :

Glucose control
Foot care
Pain control with Anticonvulsant

Pregabalin is anticonvulsant agent binds to the subunit alpha 2delta voltage-gated calcium channels to regulated influx calcium
and decreasing neurotransmitter releasing.

Treatment with pregabalin across its effective dosing range is

associated with significant, dose-related improvement in pain in
patients with DPN

LEPTICA from Dexa Medica is Bioequivalence with Originator, it

means Quality, Efficacy and Safety is equal with the originator.

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