Neuropathic pain
Gabex is indicated for the treatment of peripheral and central neuropathic pain in
adults.
Epilepsy
Gabex is indicated as adjunctive therapy in adults with partial seizures with or without
secondary generalization.
Generalized Anxiety Disorder
Gabex is indicated for the treatment of Generalized Anxiety Disorder (GAD) in adults.

Posology
The dose range is 150 to 600 mg per day given in either two or three divided doses.
Neuropathic pain
Pregabalin treatment can be started at a dose of 150 mg per day given as two or three
divided doses. Based on individual patient response and tolerability, the dose may be
increased to 300 mg per day after an interval of 3 to 7 days, and if needed, to a maximum
dose of 600 mg per day after an additional 7-day interval.

Epilepsy
Pregabalin treatment can be started with a dose o f 150 m g per day given a s two or three
divided doses. Based on individual patient response and tolerability, the dose may be
increased to 300 mg per day after 1 week. The maximum dose of 600 mg per day may be
achieved after an additional week.
Generalised Anxiety Disorder
The dose range is 150 to 600 m g per day given as t w o or three divided doses.
The need for treatment should be reassessed regularly.
Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual
patient response and tolerability, the dose may be increased to 300 mg per day after 1
week. Following an additional week the dose may be increased to 450 mg per day. The
maximum dose of 600 mg per day may be achieved after an additional week.
Discontinuation of Pregabalin
In a c c o r d a n c e with current clinical practice, if Pregabalin h a s to be discontinued it is
recommended this should be done gradually over a minimum o f 1 week independent
of the indication.
Patients with renal impairment
Pregabalin i s eliminated from the systemic circulation primarily by r e n a l excretion
as unchanged drug. As Pregabalin clearance is directly proportional to creatinine
clearance, dose reduction in patients with compromised renal function must b e
individualized according to Creatinine Clearance (CLcr), as indicated in Table1
determined using the following formula:

Pregabalin is removed effectively from plasma by haemodialysis (50% of drug in 4 hours). For patients receiving haemodialysis, the Pregabalin daily dose should be adjusted based on renal function.
In addition to the daily dose, a supplementary dose should be g i v e n immediately following every 4-hour haemodialysis treatment.

+ Supplementary dose is a single additional dose
Patients with hepatic impairment
No dose adjustment is required for patients with hepatic impairment.
Paediatric population
The safety and efficacy of Gabex in children below the age of 12 years and in adolescents
(12-17 years of age) have not been established. No data are available.
Elderlv (over 65 vears ofage) population
Elderly patients may require a dose reduction of Pregabalin due to a decreased renal function
(See patients with renal impairment).
Method of administration
Gabex™ may be taken with or without food. Gabex™ is for oral use only.

Diabetic patients
In accordance with current clinical practice, some diabetic patients who gain weight on
Pregabalin treatment may need to adjust hypoglycaemic medicinal products.
Hypersensitivity reactions
There have been reports in the postmarketing e x p eri e n c e of hypersensitivity r e a c t i o n s ,
including cases of angioedema. Pregabalin should be discontinued immediately if symptoms
of angioedema, such as facial, perioral, or upper airway swelling occur.
Dizziness,somnolence, loss of consciousness, confusion, and mental impairment
Pregabalin treatment has been associated with dizziness and somnolence, which could
increase the occurrence of accidental injury (fall) in the elderly population. There have also
been post-marketing reports of l o s s of c o n s c i o u s n e s s , confusion a n d mental
i m p a i r m e n t . Therefore, patients should be advised to exercise caution until they are
familiar w i t h the potential effects of the medicinal product.
Vision-related effects
In controlled trials, a higher proportion of patients treated with P r e g a b a l i n reported blurred
vision than did patients treated with placebo which resolved in a majority of cases with
continued dosing.
In the clinical studies where ophthalmologic testing was conducted, the i n c i d e n c e of visual
acuity reduction and visual field changes was greater in Pregabalin-treated patients than in
placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated
patients.
In the post-marketing experience, visual adverse reactions have also been reported, including
loss of vision, visual blurring or other changes of visual acuity, many of which were transient.
Discontinuation o f Pregabalin may result in resolution o r improvement of these visual
symptoms.
Renal failure
Cases of renal failure have been reported and in some cases discontinuation of Pregabalin did
show reversibility of this adverse reaction.

Withdrawal of concomitant antiepileptic medicinal products
There are insufficient data for the withdrawal of concomitant antiepileptic medicinal products,
once seizure control with Pregabalin in the add-on situation has been reached, in order to reach
monotherapy on Pregabalin.
Withdrawal symptoms
After discontinuation of short-term and long-term treatment with Pregabalin w i t h d r a w a l
symptoms have been observed in some patients. The following events have been mentioned:
insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, nervousness, depression, pain,
convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should
be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during
Pregabalin use or shortly after discontinuing Pregabalin.
Concerning d i s c o n t i n u a t i o n of long-term t r e a t m e n t of Pregabalin, d at a suggest
that the incidence and severity of withdrawal symptoms may be dose-related.
Con gestive heart failure
There have been post-marketing reports of congestive heart failure in some patients receiving
Pregabalin. These reactions are m o s t l y seen in elderly c a r d i o v a s c u l a r compromised
patients during Pregabalin treatment for a neuropathic i n d i c a t i o n . Pregabalin should be
used with caution in these patients. Discontinuation of Pregabalin may resolve the reaction.
Treatment of central neuropathic pain dueto spinal cord injury
In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse
reactions in general, central nervous system adverse reactions and especially somnolence was
increased.
This may be attributed to an additive effect due to concomitant medicinal products (e.g. antispasticity
agents) needed for this condition. This should be considered when prescribing
Pregabalin in this condition.
Suicidal ideation and behaviour
Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in
several indications. A meta-analysis of randomized placebo controlled studies of antiepileptic
drugs has also shown a small increased risk of suicidal ideation and behavior. The
mechanism of this risk is not known and the available data do not exclude the possibility of an
increased risk for Pregabalin.
Therefore patients should be monitored for signs of suicidal ideation a n d behaviors and
appropriate treatment should be considered. Patients (and caregivers of patients) should be
advised to seek medical advice should signs of suicidal ideation or behavior emerge. 

Reduced lower gastrointestinal tract function
There are post-marketing r e p o r t s of events related to reduced lower gastrointestinal tract
function (e.g., intestinal obstruction, paralytic ileus, constipation) when Pregabalin was coadministered
with medications that have the potential to produce constipation, such as opioid
analgesics.
When Pregabalin and opioids will be used in com bination, measures to prevent constipation
may be considered (especially in female patients and elderly).
Misuse, abuse potential or dependence
Cases of misuse, abuse and dependence have been reported. Caution should be exercised in
patients with a history of substance abuse and the patient should be monitored for symptoms of
Pregabalin misuse, abuse or dependence (development of tolerance, dose escalation. drugseeking
behavior have been reported).
Encephalopathy
Cases of encephalopathy have been reported, mostly in patients with underlying conditions that
may precipitate encephalopathy.

Since Pregabalin is predominantly e x c r e t e d unchanged in the urine, undergoes negligible
metabolism in humans (<2% of a dose recovered in urine as metabolites), does not inhibit drug
metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject
to, pharmacokinetic interactions.
In vivo studies and population pharmacokinetic analysis
Accordingly, in in - vivo studies no clinically relevant pharmacokinetic interactions were
observed between Pregabalin and Phenytoin, Carbamazepine, Valproic acid, Lamotrigine,
Gabapentin, Lorazepam, Oxycodone or Ethanol. Population pharmacokinetic analysis
indicated that oral anti diabetics, diuretics, insulin, Phenobarbital, Tiagabine andTopiramate
had no clinically significant effect on Pregabalin clearance.
Oral contraceptives, norethisterone and/or ethinvl oestradiol
Co-administration of Pregabalin with the oral contraceptives norethisterone and/or ethiny1
oestradiol does not influence the steady-state pharmacokinetics of either substance.

CNS influencing medical products
Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials,
multiple oral doses of Pregabalin co-administered with oxycodone, lorazepam, or ethanol did
not result in clinically important effects on respiration. In the postmarketing experience, there
are reports of respiratory failure and coma in patients taking Pregabalin and other CNS
depressant medicinal products. Pregabalin appears to be additive in the impairment of
cognitive and gross motor function caused by oxycodone.
Interactions and the elderlv
No specific p h arm aco d yn am i c interaction studies were conducted in elderly volunteers.
Interaction studies have only been performed in adults.

Women of childbearing potential I Contraception inmales and females
As the potential risk for humans is unknown, effective contraception must be used in women of
child bearing potential.
Pregnancy
Pregnancy Category C
There are no adequate data from the use of Pregabalin in pregnant women.
Studies in animals have shown reproductive toxicity (see 5.3). The potential risk for humans is
unknown.
Gabex™ should not be used during pregnancy unless clearly necessary (if the benefit to the
mother clearly outweighs the potential risk to the fetus).
Breast-feeding
It is not known if Pregabalin is excreted in the breast milk of humans; however, it is present in
the milk o f rats. Therefore, breast-feeding is not recommended d u r i n g treatment w i t h
Pregabalin.
Fertilitv
There are no clinical data on the effects of Pregabalin on female fertility.
In a clinical trial to assess the effect of Pregabalin on sperm motility, healthy male subjects were
exposed to Pregabalin at a dose of 600 mg/day. After 3 months of treatment, there were no
effects on sperm motility.
A fertility study in female rats has shown adverse reproductive effects. Fertility studies in male
Rats have shown adverse reproductive and developmental effects. The clinical relevance of these
findings is unknown.

Gabex™ may have minor or moderate influence on the ability to drive a n d use machines.
Gabex™ may cause dizziness and somnolence and therefore may influence the ability to
drive or use machines. Patients are advised not to drive, operate complex machinery or
engage in other potentially hazardous activities until it is known whether this medicinal
product affects their ability to perform these activities.

The Pregabalin clinical programme involved over 8900 patients w ho were exposed to
Pregabalin, of who over 5600 were in double- blind placebo controlled trials. The most
commonly reported adverse reactions were dizziness and somnolence. Adverse reactions were
usually mild to moderate in intensity. In all controlled studies, the discontinuation rate due to
adverse reactions was 12% for patients receiving Pregabalin and 5% for patients receiving
placebo. The most common adverse reactions re suiting in discontinuation from Pregabalin
treatment groups were dizziness and somnolence.
In the table below all adverse r e a c t i o n s , which occurred at an incidence greater than
placebo and in more than one patient, are listed by class and frequency (very common ( ≥1/10);
common (≥1/100 to <1/10); uncommon (≥1/1,000 to<1/100); rare (≥1/10,000 to <1/1,000); very
rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing
seriousness.
The adverse reactions listed may also be associated with the underlying disease and/or
concomitant medicinal products.
In the treatment of central neuropathic pain due to spinal cord injury the incidence of
Adverse reactions in general, CNS adverse reactions and especially somnolence was increased
Additional reactions reported from post-marketing experience are included in italics in the list
below.

Additional reactions reported from post-marketing experience are included in italics in the list below.

After discontinuation of short-term and long-term treatment with Pregabalin withdrawal symptoms have been observed in some patients.

The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.

Concerning discontinuation of long-term treatment of Pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.

 To report any side effect(s):

• Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)

• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222,

Exts: 2317-2356-2353-2354-2334-2340.

• Toll free phone: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc

In the post-marketing experience, the most commonly reported adverse reactions
observed when Pregabalin was taken in overdose included somnolence, confusional state,
agitation and restlessness. In rare occasions, cases of coma have been reported.
Treatment of Pregabalin overdose should include general supportive measures and may
include haemodialysis if necessary.

Pharmacotherapeutic group: Antiepileptics, other antiepileptics ATC code:
N03AX16
The active substance, Pregabalin, is a gamma-aminobutyric acid analogue ((S)-3-
(aminomethyl)-5-methylhexanoic acid).
Mechanism of action
Pregabalin binds to an auxiliary subunit (α2- δ protein) of voltage-gated calcium channels in
the central nervous system,

Clinical Efficacy and safety
Neuropathic pain
Efficacy has been shown in trials in diabetic neuropathy, p o s t herpetic neuralgia and
spinal cord injury. Efficacy has not been studied in other models of neuropathic pain.
Pregabalin has been studied in 10 controlled clinical trials of up to 13 weeks with twice a
day dosing (BID) and up to 8 weeks with three times a day (TID) dosing. Overall, the safety
and efficacy profiles for BID and TID dosing regimens were similar.
In clinical trials up to 12 weeks for both peripheral and central nemopathic pain, a reduction
in pain was seen by week 1 and was maintained throughout the treatment period.
In controlled clinical trials in peripheral neuropathic pain 35% o f the Pregabalin treated
patients and 18% of the patients on placebo had a 50% improvement in pain score.
For patients not experiencing somnolence, such an improvement was observed in 33% of
patients treated with Pregabalin and 18% of patients on placebo. For patients
who experienced somnolence t h e responder rates were 48% on Pregabalin and
16% on placebo.
In the controlled clinical trial in central neuropathic pain 22% of the Pregabalin treated
patients and 7% of the patients on placebo had a 50% improvement in pain score.

Epilepsy
Adjunctive Treatment
Pregabalin has been studied in 3 controlled clinical trials of 12 week duration with either
twice a day dosing (BID) or three times a day (TID) dosing. Overall, the safety and efficacy
profiles for BID and TID dosing regimens were similar.
A reduction in seizure frequency was observed by Week.
Monotherapy (newly diagnosed patients)
Pregabalin has been studied in 1 controlled clinical trial of 56 week duration with twice a
day dosing (BID). Pregabalin did not achieve non-inferiority to lamotrigine based on the 6-
month seizure freedom endpoint. Pregabalin and lamotrigine were similarly safe and well
tolerated.
Generalized Anxiety Disorder
Pregabalin has been studied in 6 controlled trials of 4-6 week duration, an elderly study of
8 week duration and a long-term relapse prevention study with a double blind relapse
prevention phase of 6 months duration.
Relief of the symptoms of GAD as reflected by the Hamilton Anxiety Rating Scale
(HAM- A) was observed by Week 1.
In controlled clinical trials (4-8 week duration) 52% of the Pregabalin treated patients and
38% of the patients on placebo had at least a 50% improvement in HAM-A total score from
baseline to endpoint.
In controlled trials, a higher proportion of patients treated with Pregabalin reported blurred
vision than did patients treated with placebo which resolved in a majority of cases with
continued dosing. Ophthamologic testing (including visual acuity testing, formal visual
field testing and dilated funduscopic examination) was conducted in over 3600 patients
within controlled clinical trials.
In these patients, visual acuity was reduced in 6.5% of patients treated with Pregabalin,
and 4.8% of placebo-treated patients. Visual field changes were detected in 12.4% of
P r e g a b a l i n treated, and 11.7% of placebo-treated patients. Funduscopic changes were
observed in 1.7% of Pregabalin-treated and 2.1% of placebo-treated patients.

Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with
epilepsy receiving anti-epileptic drugs and patients with chronic pain.
Absorption
Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma
concentrations occurring within 1 hour following both single and multiple dose
administration.
Pregabalin oral bioavailability is estimated to be ≥90% and is independent o f dose.
Following repeated administration, steady state is achieved within 24 to 48 hours. The rate
of Pregabalin absorption is decreased when given with food resulting in a decrease in Cmax
by approximately
25-30% and a delay in t max to approximately 2.5 hours. However, administration of
Pregabalin with food has no clinically significant effect on the extent of Pregabalin
absorption.
Distribution
In preclinical studies, Pregabalin has been shown to cross the blood brain barrier in mice,
rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in
the milk of lactating rats. In humans, the apparent volume of distribution of Pregabalin
following oral administration is approximately 0.561/kg. Pregabalin is not bound to plasma
proteins.
Biotransformation
Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled
Pregabalin, approximately 9 8 % of t h e radio activity recovered in t h e urine was
unchanged Pregabalin.
The N-methylated derivative of Pregabalin, the major metabolite of Pregabalin found in
urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of
racemisation of Pregabalin S-enantiomer to the R-enantiomer.

Elimination
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as
unchanged drug.
Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma c l e a r a n c e and renal
clearance are directly proportional to creatinine clearance.
Dose a d j u s t m e n t i n patients with reduced renal function o r undergoing haemodialysis
is necessary.
Linearity/non-linearity
Pregabalin pharmacokinetics is linear over the recommended daily dose range. Inter-subject
pharmacokinetic variability for Pregabalin is low (<20%). Multiple dose pharmacokinetics
is predictable from single-dose data. Therefore, there is no need for routine monitoring of
plasma concentrations of Pregabalin.
Gender
Clinical trials indicate that gender does not have a clinically significant influence on the
plasma concentrations of Pregabalin.
Renal impairment
Pregabalin clearance is directly proportional to creatinine clearance. In addition, Pregabalin
is effectively removed from plasma by haemodialysis (following 4 hour haemodialysis
treatment plasma Pregabalin concentrations are reduced by approximately 50%). Because
renal elimination is the major elimination pathway, dose reduction in patients with renal
impairment and dose supplementation following haemodialysis is necessary
Hepatic impairment
No specific pharmacokinetic studies were carried out in patients with impaired
liver function. Since Pregabalin does not undergo significant metabolism and is
excreted predominantly a s unchanged drug in the urine, impaired liver function
would not be expected to significantly alter Pregabalin plasma concentrations.

Elderly (over 65 years of age)
Pregabalin clearance tends to decrease with increasing age. This decrease in Pregabalin oral
clearance is consistent with decreases in creatinine clearance associated with increasing age.
Reduction of Pregabalin dose may be required in patients who have age related compromised
renal function.

In conventional safety pharmacology studies in animals, Pregabalin was well-tolerated at
clinically relevant doses. In repeated dose toxicity studies in rats and monkeys CNS effects
were observed, including hypoactivity, hyperactivity and ataxia. An increased incidence of
retinal atrophy commonly observed in aged albino rats was seen after long term exposure to
Pregabalin at exposures5 times the mean human exposure at the maximum recommended
clinical dose.
Pregabalin was not teratogenic in mice, rats or rabbits. Foetal toxicity in rats and rabbits
occurred only at exposures sufficiently above human exposure. In prenatal/postnatal toxicity
studies, Pregabalin induced offspring developmental toxicity in rats at exposures >2 times the
maximum recommended human exposure.
Adverse effects on fertility in male and female rats were only observed at exposures sufficiently
in excess of therapeutic exposure. Adverse effects on male reproductive organs and sperm
parameters were reversible and occurred only at exposures sufficiently in excess of therapeutic
exposure or were associated with spontaneous degenerative processes in male reproductive
organs in the rat. Therefore the effects were considered of little or no clinical relevance.
Pregabalin is not genotoxic based on results of a battery of in vitro and in vivo tests.
Two-year carcinogenicity studies with Pregabalin were conducted in rats and mice. No tumors
were observed in rats at exposures up to 24 times the mean human exposure at the maximum
recommended clinical dose of 600 mg/day. In mice, no increased incidence of tumors was
found at exposures similar to them in human exposure, but an increased incidence of
haemangiosarcoma was observed at higher exposures. The non-genotoxic mechanism of
Pregabalin-induced t u m o u r f o r m a t i o n i n mice i n v o l v e s platelet changes and associated
endothelial cell proliferation. These platelet changes were not present in rats or in humans based
on short term and limited long term clinical data. There is no evidence to suggest an associated
risk to humans.
In juvenile rats the types of toxicity do not differ qualitatively from those observed in adult rats.
However, juvenile rats are more sensitive. At therapeutic exposures, there was evidence of CNS
clinical signs of hyperactivity and bruxism and some changes in growth (transient body weight
gain suppression). Effects on the oestrus cycle were observed at 5-fold the human therapeutic exposure. Reduced acoustic startle response was observed in juvenile rats 1-2 weeks
after exposure at >2 times the human therapeutic exposure. Nine weeks after exposure,
this effect was no longer observable.

Pregelatinized starch, Talc, and Gelatin that containsSodium lauryl sulphate and
Titanium dioxide. Gabex™ 300mg capsules also contain iron oxide red.

Not applicable.

Keep out of the reach and sight of children.
Do not store above 30 °C.
Store in the original package.
Store in dry place.
Do not use this medicine after the expiry date which is stated on the carton.

Pregabalin 300 mg capsules are packed as Aluminium-PVC/PVDC blisters containing 30 (3x10)
hard capsules in outer carton with Patient Information Leaflet.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures will help to protect the
environment.