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GABAPENTIN DOUBLE-E PHARMA 300 MG CAPSULES

Active substance(s): GABAPENTIN

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT
Gabapentin DOUBLE-E PHARMA 300 mg capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 300mg capsule contains 300 mg gabapentin.
Excipients:
Each 300 mg capsule contains 50.50 mg lactose (as monohydrate).
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Hard capsules (capsules):
Yellow hard capsule, imprinted with “300” and containing a white crystalline
powder.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Epilepsy
Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with
and without secondary generalization in adults and children aged 6 years and above
(see section 5.1).
Gabapentin is indicated as monotherapy in the treatment of partial seizures with and
without secondary generalization in adults and adolescents aged 12 years and above.
Treatment of peripheral neuropathic pain
Gabapentin is indicated for the treatment of peripheral neuropathic pain such as
painful diabetic
neuropathy and post-herpetic neuralgia in adults.

4.2

Posology and method of administration
For oral use.
Gabapentin can be given with or without food and should be swallowed whole
with sufficient fluid-intake (e.g. a glass of water).
For all indications a titration scheme for the initiation of therapy is described
in Table 1, which is recommended for adults and adolescents aged 12 years
and above. Dosing instructions for children under 12 years of age are provided
under a separate sub-heading later in this section.
Table 1
DOSING CHART – INITIAL TITRATION
Day 1
Day 2
300 mg once a
300 mg two times a day
day

Day 3
300 mg three times a
day

Discontinuation of gabapentin
In accordance with current clinical practice, if gabapentin has to be
discontinued it is recommended this should be done gradually over a minimum
of 1 week independent of the indication.
Epilepsy
Epilepsy typically requires long-term therapy. Dosage is determined by the
treating physician according to
individual tolerance and efficacy.
Adults and adolescents:
In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy
may be initiated by titrating the dose as described in Table 1 or by
administering 300 mg three times a day (TID) on Day 1. Thereafter, based on
individual patient response and tolerability, the dose can be further increased
in 300 mg/day increments every 2-3 days up to a maximum dose of 3600
mg/day. Slower titration of gabapentin dosage may be appropriate for
individual patients. The minimum time to reach a dose of 1800 mg/day is one
week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is
a total of 3 weeks.
Dosages up to 4800 mg/day have been well tolerated in long-term open-label
clinical studies. The total daily dose should be divided in three single doses,
the maximum time interval between the doses should not exceed 12 hours to
prevent breakthrough convulsions.
Children aged 6 years and above:
The starting dose should range from 10 to 15 mg/kg/day and the effective dose
is reached by upward titration over a period of approximately three days. The
effective dose of gabapentin in children aged 6 years and older is 25 to 35
mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a
longterm clinical study. The total daily dose should be divided in three single
doses, the maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize
gabapentin therapy. Further, gabapentin may be used in combination with
other antiepileptic medicinal products without concern for alteration of the
plasma concentrations of gabapentin or serum concentrations of other
antiepileptic medicinal products.
Peripheral neuropathic pain
Adults
The therapy may be initiated by titrating the dose as described in Table 1.
Alternatively, the starting dose is 900 mg/day given as three equally divided
doses. Thereafter, based on individual patient response and tolerability, the
dose can be further increased in 300 mg/day increments every 2-3 days up to a
maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be
appropriate for individual patients.
The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400
mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.
In the treatment of peripheral neuropathic pain such as painful diabetic
neuropathy and post-herpetic neuralgia, efficacy and safety have not been
examined in clinical studies for treatment periods longer than 5 months. If a
patient requires dosing longer than 5 months for the treatment of peripheral
neuropathic pain, the treating physician should assess the patient's clinical
status and determine the need for additional therapy.
Instruction for all areas of indication
In patients with poor general health, i.e., low body weight, after organ
transplantation etc., the dose should be titrated more slowly, either by using
smaller dosage strengths or longer intervals between dosage increases.
Use in elderly patients (over 65 years of age)
Elderly patients may require dosage adjustment because of declining renal
function with age (see Table 2).
Somnolence, peripheral oedema and asthenia may be more frequent in elderly
patients.
Use in patients with renal impairment
Dosage adjustment is recommended in patients with compromised renal
function as described in Table 2 and/or those undergoing haemodialysis.
Gabapentin 100 mg capsules can be used to follow dosing recommendations
for patients with renal insufficiency.
Table 2
DOSAGE OF GABAPENTIN IN ADULTS BASED ON RENAL
FUNCTION
Creatinine Clearance (ml/min)
Total Daily Dosea (mg/day)
900-3600
≥ 80
50-79
600-1800
30-49
300-900
15-29
150b -600
c
<15
150b -300

a Total daily dose should be administered as three divided doses. Reduced
dosages are for patients with renal impairment (creatinine clearance < 79
ml/min).
b To be administered as 300 mg every other day.
c For patients with creatinine clearance <15 ml/min, the daily dose should be
reduced in proportion to creatinine clearance (e.g., patients with a creatinine
clearance of 7.5 ml/min should receive one-half the daily dose that patients
with a creatinine clearance of 15 ml/min receive).
Use in patients undergoing haemodialysis
For anuric patients undergoing haemodialysis who have never received
gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of
gabapentin following each 4 hours of haemodialysis, is recommended.
On dialysis-free days, there should be no treatment with gabapentin.
For renally impaired patients undergoing haemodialysis, the maintenance dose
of gabapentin should be based on the dosing recommendations found in Table
2. In addition to the maintenance dose, an additional 200 to 300 mg dose
following each 4-hour haemodialysis treatment is recommended.
4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipients.

4.4

Special warnings and precautions for use
Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomised placebo
controlled trials of anti-epileptic drugs has also shown a small increased risk of
suicidal ideation and behaviour. The mechanism of this risk is not known and the
available data do not exclude the possibility of an increased risk for gabapentin.
Therefore patients should be monitored for signs of suicidal ideation and behaviours
and appropriate treatment should be considered. Patients (and caregivers of patients)
should be advised to seek medical advice should signs of suicidal ideation or
behaviour emerge.
If a patient develops acute pancreatitis under treatment with gabapentin,
discontinuation of gabapentin should be considered (see section 4.8).
Although there is no evidence of rebound seizures with gabapentin, abrupt
withdrawal of anticonvulsant agents in epileptic patients may precipitate status
epilepticus (see section 4.2).
As with other antiepileptic medicinal products, some patients may experience an
increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in
treatment refractive patients on more than one anti-epileptic, in order to reach
gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective against primary generalized seizures such as
absences and may aggravate these seizures in some patients. Therefore, gabapentin
should be used with caution in patients with mixed seizures including absences.

No systematic studies in patients 65 years or older have been conducted with
gabapentin. In one double blind study in patients with neuropathic pain, somnolence,
peripheral oedema and asthenia occurred in a somewhat higher percentage in patients
aged 65 years or above, than in younger patients. Apart from these findings, clinical
investigations in this age group do not indicate an adverse event profile different from
that observed in younger patients.
The effects of long-term (greater than 36 weeks) gabapentin therapy on learning,
intelligence, and development in children and adolescents have not been adequately
studied. The benefits of prolonged therapy must therefore be weighed against the
potential risks of such therapy.
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
Severe, life-threatening, systemic hypersensitivity reactions such as Drug rash with
eosinophilia and systemic symptoms (DRESS) have been reported in patients taking
antiepileptic drugs including gabapentin (see section 4.8).
It is important to note that early manifestations of hypersensitivity, such as fever or
lymphadenopathy, may be present even though rash is not evident. If such signs or
symptoms are present, the patient should be evaluated immediately. Gabapentin
should be discontinued if an alternative etiology for the signs or symptoms cannot be
established.
Laboratory tests
False positive readings may be obtained in the semi-quantitative determination of
total urine protein by dipstick tests. It is therefore recommended to verify such a
positive dipstick test result by methods based on a different analytical principle such
as the Biuret method, turbidimetric or dye-binding methods, or to use these
alternative methods from the beginning.
Gabapentin capsules contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
should not take Gabapentin capsules.

4.5

Interaction with other medicinal products and other forms of interaction
In a study involving healthy volunteers (N=12), when a 60 mg controlled-release
morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule,
mean gabapentin AUC increased by 44% compared to gabapentin administered
without morphine. Therefore, patients should be carefully observed for signs of CNS
depression, such as somnolence, and the dose of gabapentin or morphine should be
reduced appropriately.
No interaction between gabapentin and phenobarbital, phenytoin, valproic acid, or
carbamazepine has been observed.
Gabapentin steady-state pharmacokinetics are similar for healthy subjects and
patients with epilepsy receiving these anti-epileptic agents.
Coadministration of gabapentin with oral contraceptives containing norethindrone
and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either
component.

Coadministration of gabapentin with antacids containing aluminium and magnesium,
reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be
taken at the earliest two hours following antacid administration.
Renal excretion of gabapentin is unaltered by probenecid.
A slight decrease in renal excretion of gabapentin that is observed when it is
coadministered with cimetidine is not expected to be of clinical importance.

4.6

Pregnancy and lactation
Risk related to epilepsy and antiepileptic medicinal products in general
The risk of birth defects is increased by a factor of 2 – 3 in the offspring of mothers
treated with an antiepileptic medicinal product. Most frequently reported are cleft lip,
cardiovascular malformations and neural tube defects. Multiple antiepileptic drug
therapy may be associated with a higher risk of congenital malformations than
monotherapy, therefore it is important that monotherapy is practised whenever
possible. Specialist advice should be given to women who are likely to become
pregnant or who are of childbearing potential and the need for antiepileptic treatment
should be reviewed when a woman is planning to become pregnant. No sudden
discontinuation of antiepileptic therapy should be undertaken as this may lead to
breakthrough seizures, which could have serious consequences for both mother and
child. Developmental delay in children of mothers with epilepsy has been observed
rarely. It is not possible to differentiate if the developmental delay is caused by
genetic, social factors, maternal epilepsy or the antiepileptic therapy.
Risk related to gabapentin
There are no adequate data from the use of gabapentin in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). The potential
risk for humans is unknown. Gabapentin should not be used during pregnancy unless
the potential benefit to the mother clearly outweighs the potential risk to the foetus.
No definite conclusion can be made as to whether gabapentin is associated with an
increased risk of congenital malformations when taken during pregnancy, because of
epilepsy itself and the presence of concomitant antiepileptic medicinal products
during each reported pregnancy.
Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is
unknown, caution should be exercised when gabapentin is administered to a breastfeeding mother. Gabapentin should be used in breast-feeding mothers only if the
benefits clearly outweigh the risks.

4.7

Effects on ability to drive and use machines
Gabapentin may have minor or moderate influence on the ability to drive and use
machines. Gabapentin acts on the central nervous system and may cause drowsiness,
dizziness or other related symptoms.
Even, if they were only of mild or moderate degree, these undesirable effects could be
potentially dangerous in patients driving or operating machinery. This is especially
true at the beginning of the treatment and after increase in dose.

4.8

Undesirable effects

The adverse reactions observed during clinical studies conducted in epilepsy
(adjunctive and monotherapy) and neuropathic pain have been provided in a single list
below by class and frequency (very common ( 1/10); common ( 1/100 to< 1/10);
uncommon ( 1/1000 to < 1/100); rare ( 1/10000 to < 1/1000); very rare (< 1/10000).
Where an adverse reaction was seen at different frequencies in clinical studies, it was
assigned to the highest frequency reported.
Additional reactions reported from post-marketing experience are included as
frequency Not known (cannot be estimated from the available data) in italics in the
list below.
Within each frequency grouping, undesirable effects are presented in order of
decreasing seriousness.
Body System
Infections and infestations
Very Common
Common
Blood and the lymphatic system disorders
Common
Not known
Immune system disorders
Uncommon
Not Known

Metabolism and Nutrition Disorders
Common
Psychiatric disorders
Common

Not known
Nervous system disorders
Very Common
Common

Uncommon
Not known
Eye disorders
Common
Ear and Labyrinth disorders
Common
Not known

Adverse drug reactions
Viral infection
Pneumonia, respiratory infection, urinary
tract infection, infection, otitis media
leucopenia
thrombocytopenia
allergic reactions (e.g. urticaria)
hypersensitivity syndrome, a systemic
reaction with a variable presentation that
can include fever, rash, hepatitis,
lymphadenopathy, eosinophilia, and
sometimes other signs and symptoms
anorexia, increased appetite
hostility, confusion and emotional lability,
depression, anxiety, nervousness, thinking
abnormal
hallucinations
somnolence, dizziness, ataxia
convulsions, hyperkinesias, dysarthria,
amnesia, tremor, insomnia, headache,
sensations such as paresthesia, hypaesthesia,
coordination abnormal, nystagmus,
increased, decreased, or absent reflexes
hypokinesia
other movement disorders (e.g.
choreoathetosis, dyskinesia, dystonia)
visual disturbances such as amblyopia,
diplopia
vertigo
tinnitus

Cardiac disorders
Uncommon
palpitations
Vascular disorders
Common
hypertension, vasodilatation
Respiratory, thoracic and mediastinal disorders
Common
dyspnoea, bronchitis, pharyngitis, cough,
rhinitis
Gastrointestinal disorders
Common
vomiting, nausea, dental abnormalities,
gingivitis, diarrhea, abdominal pain,
dyspepsia, constipation, dry mouth or throat,
flatulence
Not known
pancreatitis
Hepatobiliary disorders
Not known
hepatitis, jaundice
Skin and subcutaneous tissue disorders
Common
facial oedema, purpura most often described
as bruises resulting from physical trauma,
rash, pruritus, acne
Not known
Stevens-Johnson syndrome, angioedema,
erythema multiforme, alopecia, drug rash
with eosinophilia and systemic symptoms
(see section 4.4)
Musculoskeletal, connective tissue and bone disorders
Common
arthralgia, myalgia, back pain, twitching
Not known
myoclonus
Renal and urinary disorder
Not known
acute renal failure, incontinence
Reproductive system and breast disorders
Common
impotence
Not known
breast hypertrophy, gynaecomastia
General disorders and administration site conditions
Very Common
fatigue, fever
Common
peripheral oedema, abnormal gait, asthenia,
pain, malaise, flu syndrome
Uncommon
generalized oedema
Not known
withdrawal reactions (mostly anxiety,
insomnia, nausea, pains, sweating), chest
pain. Sudden unexplained deaths have been
reported where a causal relationship to
treatment with gabapentin has not been
established.
Investigations
Common
WBC (white blood cell count) decreased,
weight gain
Uncommon
elevated liver function tests SGOT (AST),
SGPT (ALT) and bilirubin
Not known
blood glucose fluctuations in patients with
diabetes
Injury and poisoning
Common
accidental injury, fracture, abrasion

Under treatment with gabapentin cases of acute pancreatitis were reported. Causality
with gabapentin is unclear (see section 4.4).
In patients on haemodialysis due to end-stage renal failure, myopathy with elevated
creatine kinase levels has been reported.
Respiratory tract infections, otitis media, convulsions and bronchitis were reported
only in clinical studies in children. Additionally, in clinical studies in children,
aggressive behaviour and hyperkinesias were reported commonly.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Acute, life-threatening toxicity has not been observed with gabapentin overdoses of
up to 49 grams.
Symptoms of the overdoses included dizziness, double vision, slurred speech,
drowsiness, lethargy and mild diarrhoea. All patients recovered fully with supportive
care. Reduced absorption of gabapentin at higher doses may limit drug absorption at
the time of overdosing and, hence, minimise toxicity from overdoses.
Overdoses of gabapentin, particularly in combination with other CNS depressant
medications, may result in coma.
Although gabapentin can be removed by haemodialysis, based on prior experience it
is not usually required. However, in patients with severe renal impairment,
haemodialysis may be indicated.
An oral lethal dose of gabapentin was not identified in mice and rats given doses as
high as 8000 mg/kg.
Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis,
hypoactivity, or excitation.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic groups: Other antiepileptics ATC code: N03AX12
The precise mechanism of action of gabapentin is not known.
Gabapentin is structurally related to the neurotransmitter GABA (gammaaminobutyric acid) but its mechanism of action is different from that of several other
active substances that interact with GABA synapses including valproate, barbiturates,
benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA
agonists, and GABA prodrugs. In vitro studies with radiolabeled gabapentin have
characterized a novel peptide binding site in rat brain tissues including neocortex and

hippocampus that may relate to anticonvulsant and analgesic activity of gabapentin
and its structural derivatives.
The binding site for gabapentin has been identified as the alpha2-delta subunit of
voltage-gated calcium channels.
Gabapentin at relevant clinical concentrations does not bind to other common drug or
neurotransmitter receptors of the brain including GABAA, GABAB, benzodiazepine,
glutamate, glycine or N-methyl-daspartate receptors.
Gabapentin does not interact with sodium channels in vitro and so differs from
phenytoin and carbamazepine. Gabapentin partially reduces responses to the
glutamate agonist N-methyl-D-aspartate (NMDA) in some test systems in vitro, but
only at concentrations greater than 100 M, which are not achieved in vivo.
Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro.

μ

Gabapentin administration to rats increases GABA turnover in several brain regions
in a manner similar to valproate sodium, although in different regions of brain. The
relevance of these various actions of gabapentin to the anticonvulsant effects remains
to be established. In animals, gabapentin readily enters the brain and prevents seizures
from maximal electroshock, from chemical convulsants including inhibitors of
GABA synthesis, and in genetic models of seizures.
A clinical trial of adjunctive treatment of partial seizures in paediatric subjects
ranging in age from 3 to 12 years, showed a numerical but not statistically significant
difference in the 50% responder rate in favour of the gabapentin group compared to
placebo. Additional post-hoc analyses of the responder rates by age did not reveal a
statistically significant effect of age, either as a continuous or dichotomous variable
(age groups 3-5 and 6-12 years).
The data from this additional post-hoc analysis are summarised in the table below:
Response ( ≥ 50% Improved) by Treatment and Age MITT* Population
Age Category

Placebo

Gabapentin

P-Value

< 6 Years Old

4/21 (19.0%)

4/17 (23.5%)

0.7362

6 to 12 Years
Old

17/99 (17.2%)

20/96 (20.8%)

0.5144

*The modified intent to treat population was defined as all patients randomised to
study medication who also had evaluable seizure diaries available for 28 days during
both the baseline and double-blind phases.

5.2

Pharmacokinetic properties
Absorption
Following oral administration, peak plasma gabapentin concentrations are observed
within 2 to 3 hours.
Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with
increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%.
Food, including a high-fat diet, has no clinically significant effect on gabapentin
pharmacokinetics.

Gabapentin pharmacokinetics are not affected by repeated administration. Although
plasma gabapentin concentrations were generally between 2 g/ml and 20 g/ml in
clinical studies, such concentrations were not predictive of safety or efficacy.
Pharmacokinetic parameters are given in Table 3.

μ

μ

Table 3
Summary of gabapentin mean (%CV) steady-state pharmacokinetic parameters
following every eight hours administration

Pharmacokinetic

300 mg

400 mg

800 mg

parameter

(N = 7)

(N = 14)

(N=14)

Mean

%CV

Mean

%CV

Mean

%CV

Cmax ( g/ml)

4.02

(24)

5.74

(38)

8.71

(29)

tmax (hr)

2.7

(18)

2.1

(54)

1.6

(76)

T1/2 (hr)

5.2

(12)

10.8

(89)

10.6

(41)

AUC (0-8)

24.8

(24)

34.5

(34)

51.4

(27)

NA

NA

47.2

(25)

34.4

(37)

μ

g•hr/ml)

μ

Ae% (%)

Cmax = Maximum steady state plasma concentration
tmax = Time for Cmax
T1/2 = Elimination half-life
AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours
postdose
Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose
NA = Not available

Distribution
Gabapentin is not bound to plasma proteins and has a volume of distribution equal to
57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid
(CSF) are approximately 20% of corresponding steady-state trough plasma
concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Metabolism
There is no evidence of gabapentin metabolism in humans. Gabapentin does not
induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination
Gabapentin is eliminated unchanged solely by renal excretion. The elimination halflife of gabapentin is independent of dose and averages 5 to 7 hours.

In elderly patients, and in patients with impaired renal function, gabapentin plasma
clearance is reduced.
Gabapentin elimination-rate constant, plasma clearance, and renal clearance are
directly proportional to creatinine clearance.
Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients
with compromised renal function or undergoing haemodialysis is recommended (see
section 4.2).
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects
between the ages of 1 month and 12 years. In general, plasma gabapentin
concentrations in children> 5 years of age are similar to those in adults when dosed
on a mg/kg basis.
Linearity/Non-linearity
Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose
which imparts nonlinearity to pharmacokinetic parameters which include the
bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics
(pharmacokinetic parameters which do not include F such as CLr and T1/2), are best
described by linear pharmacokinetics. Steady state plasma gabapentin concentrations
are predictable from single-dose data.

5.3

Preclinical safety data
Carcinogenesis
Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats
at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in
the incidence of pancreatic acinar cell tumours was found only in male rats at the
highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg are 10 times
higher than plasma concentrations in humans given 3600 mg/day. The pancreatic
acinar cell tumours in male rats are low-grade malignancies, did not affect survival,
did not metastasize or invade surrounding tissue, and were similar to those seen in
concurrent controls. The relevance of these pancreatic acinar cell tumours in male rats
to carcinogenic risk in humans is unclear.
Mutagenesis
Gabapentin demonstrated no genotoxic potential. It was not mutagenic in vitro in
standard assays using bacterial or mammalian cells. Gabapentin did not induce
structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not
induce micronucleus formation in the bone marrow of hamsters.
Impairment of Fertility
No adverse effects on fertility or reproduction were observed in rats at doses up to
2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2
of body surface area basis).
Teratogenesis

Gabapentin did not increase the incidence of malformations, compared to controls, in
the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively,
the daily human dose of 3600 mg, (four, five or eight times, respectively, the human
daily dose on a mg/m2 basis).
Gabapentin induced delayed ossification in the skull, vertebrae, forelimbs, and
hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred
when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during
organogenesis and in rats given 500, 1000, or 2000 mg/kg prior to and during mating
and throughout gestation. These doses are approximately 1 to 5 times the human dose
of 3600 mg on a mg/m2 basis.
No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2
of the daily human dose on a mg/m2 basis).
An increased incidence of hydroureter and/or hydronephrosis was observed in rats
given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day
in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal
study. The significance of these findings is unknown, but they have been associated
with delayed development. These doses are also approximately 1 to 5 times the
human dose of 3600 mg on a mg/m2 basis.
In a teratology study in rabbits, an increased incidence of post-implantation fetal loss,
occurred in doses given 60, 300, and 1500 mg/kg/day during organogenesis. These
doses are approximately 1/4 to 8 times the daily human dose of 3600 mg on a mg/m2
basis.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Capsules fill:
lactose monohydrate;
maize starch;
talc.
Capsule shell:
gelatin;
titanium dioxide (E171);
yellow iron oxide (E172).
Printing ink:
shellac;
iron oxide black (E172);
propylene glycole.

6.2

Incompatibilities

Not applicable

6.3

Shelf life
Three years

6.4

Special precautions for storage
Do not store above 30°C.

6.5

Nature and contents of container
PVC/aluminium foil blister packs
Supplied in packs of 100 capsules.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
DOUBLE-E PHARMA LTD.
7th Floor, Hume House, Ballsbridge
Dublin 4
Ireland

8

MARKETING AUTHORISATION NUMBER(S)
PL 39891/0002

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
07/08/2013

10

DATE OF REVISION OF THE TEXT
21/02/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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