Lyribastad 225 mg Kapsel, hård

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

21-04-2018

Produktens egenskaper Produktens egenskaper (SPC)

02-07-2020

Aktiva substanser:
pregabalin
Tillgänglig från:
STADA Arzneimittel AG
ATC-kod:
N03AX16
INN (International namn):
pregabalin
Dos:
225 mg
Läkemedelsform:
Kapsel, hård
Sammansättning:
laktosmonohydrat Hjälpämne; pregabalin 225 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 200 x 1 kapslar (endos); Blister, 210 x 1 kapslar (endos); Blister, 100 x 1 kapslar (endos); Blister, 70 x 1 kapslar (endos); Blister, 60 x 1 kapslar (endos); Blister, 14 x 1 kapslar (endos); Blister, 30 x 1 kapslar (endos); Blister, 28 x 1 kapslar (endos); Blister, 56 x 1 kapslar (endos); Blister, 28 kapslar; Blister, 30 kapslar; Blister, 56 kapslar; Blister, 60 kapslar; Blister, 70 kapslar; Blister, 100 kapslar; Blister, 200 kapslar; Blister, 210 kapslar; Blister, 14 kapslar
Bemyndigande status:
Godkänd
Godkännandenummer:
55166
Tillstånd datum:
2017-12-15

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

18-06-2021

Produktens egenskaper Produktens egenskaper - engelska

18-06-2021

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

15-12-2017

Läs hela dokumentet

Package leaflet: Information for the user

Lyribastad 25 mg capsules, hard

Lyribastad 50 mg capsules, hard

Lyribastad 75 mg capsules, hard

Lyribastad 100 mg capsules, hard

Lyribastad 150 mg capsules, hard

Lyribastad 200 mg capsules, hard

Lyribastad 225 mg capsules, hard

Lyribastad 300 mg capsules, hard

pregabalin

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm

them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What <Product name> is and what it is used for

What you need to know before you take <Product name>

How to take <Product name>

Possible side effects

How to store <Product name>

Contents of the pack and other information

1. What <Product name> is and what it is used for

<Product name> belongs to a group of medicines used to treat epilepsy, neuropathic pain and

Generalised Anxiety Disorder (GAD) in adults.

Peripheral and central neuropathic pain: <Product name> is used to treat long lasting pain

caused by damage to the nerves. A variety of diseases can cause peripheral neuropathic pain,

such as diabetes or shingles. Pain sensations may be described as hot, burning, throbbing,

shooting, stabbing, sharp, cramping, aching, tingling, numbness, pins and needles. Peripheral

and central neuropathic pain may also be associated with mood changes, sleep disturbance,

fatigue (tiredness), and can have an impact on physical and social functioning and overall

quality of life.

Epilepsy: <Product name> is used to treat a certain form of epilepsy (partial seizures with or

without secondary generalisation) in adults. Your doctor will prescribe <Product name> for you

to help treat your epilepsy when your current treatment is not controlling your condition. You

should take <Product name> in addition to your current treatment. <Product name> is not

intended to be used alone, but should always be used in combination with other anti-epileptic

treatment.

Generalised Anxiety Disorder: <Product name> is used to treat Generalised Anxiety

Disorder (GAD). The symptoms of GAD are prolonged excessive anxiety and worry that are

difficult to control. GAD can also cause restlessness or feeling keyed up or on edge, being

easily fatigued (tired), having difficulty concentrating or mind going blank, feeling irritable,

having muscle tension or sleep disturbance. This is different to the stresses and strains of

everyday life.

2. What you need to know before you take <Product name>

DO NOT take <Product name>

If you are allergic to pregabalin or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking <Product name>

Some patients taking <Product name> have reported symptoms suggesting an allergic

reaction. These symptoms include swelling of the face, lips, tongue, and throat, as well as

diffuse skin rash. Should you experience any of these reactions, you should contact your

physician immediately.

<Product name> has been associated with dizziness and somnolence, which could

increase the occurrence of accidental injury (fall) in elderly patients. Therefore, you should

be careful until you are used to any effect the medicine might have.

<Product name> may cause blurring or loss of vision, or other changes in eyesight, many

of which are temporary. You should immediately tell your doctor if you experience any

changes in your vision.

Some patients with diabetes who gain weight while taking pregabalin may need an

alteration in their diabetic medicines.

Certain side effects may be more common, such as sleepiness, because patients with

spinal cord injury may be taking other medicines to treat, for example, pain or spasticity,

that have similar side effects to pregabalin and the severity of these effects may be

increased when taken together.

There have been reports of heart failure in some patients when taking <Product name>;

these patients were mostly elderly with cardiovascular conditions. Before taking this

medicine you should tell your doctor if you have a history of heart disease.

There have been reports of kidney failure in some patients when taking <Product name>. If

while taking <Product name> you notice decreased urination, you should tell your doctor as

stopping the medicine may improve this.

A small number of people being treated with anti-epileptics such as <Product name> have

had thoughts of harming or killing themselves. If at any time you have these thoughts,

immediately contact your doctor.

When <Product name> is taken with other medicines that may cause constipation (such as

some types of pain medicines) it is possible that gastrointestinal problems may occur (e.g.,

constipation, blocked or paralysed bowel). Tell your doctor if you experience constipation,

especially if you are prone to this problem.

Before taking this medicine you should tell your doctor if you have a history of alcoholism

or any drug abuse or dependence. Do not take more medicine than prescribed.

There have been reports of convulsions when taking <Product name> or shortly after

stopping <Product name>. If you experience a convulsion, contact your doctor immediately.

There have been reports of reduction in brain function (encephalopathy) in some patients

taking <Product name> when they have other conditions. Tell your doctor if you have a

history of any serious medical conditions, including liver or kidney disease.

There have been reports of breathing difficulties. If you have nervous system disorders,

respiratory disorders, renal impairment, or you are older than 65, your doctor may prescribe

you a different dosing regimen. Contact your doctor if you experience trouble breathing or

shallow breaths.

Children and adolescents

The safety and efficacy in children and adolescents (under 18 years of age) has not been

established and therefore, pregabalin should not be used in this age group.

Other medicines and <Product name>

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines.

<Product name> and certain other medicines may influence each other (interaction). When

taken with certain other medicines, which have sedative effects (including opioids), <Product

name> may potentiate these effects, and could lead to respiratory failure, coma and death.

The degree of dizziness, sleepiness and decreased concentration may be increased if

<Product name> is taken together with medicines containing:

Oxycodone – (used as a painkiller)

Lorazepam – (used for treating anxiety)

Alcohol

<Product name> may be taken with oral contraceptives.

<Product name> with food, drink and alcohol

<Product name> capsules may be taken with or without food.

It is advised not to drink alcohol while taking <Product name>.

Pregnancy and breast-feeding

<Product name> should not be taken during pregnancy or when breast-feeding, unless you

are told otherwise by your doctor. Effective contraception must be used by women of

child-bearing potential. If you are pregnant or breast-feeding, think you may be pregnant or are

planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

<Product name> may produce dizziness, sleepiness and decreased concentration. You should

not drive, operate complex machinery or engage in other potentially hazardous activities until

you know whether this medicine affects your ability to perform these activities.

<Product name> contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your

doctor before taking this medicine.

3. How to take <Product name>

Always take this medicine exactly as your doctor has told you. Check with your doctor or

pharmacist if you are not sure.

Your doctor will determine what dose is appropriate for you.

<Product name> is for oral use only.

Peripheral and central neuropathic pain, epilepsy or Generalised Anxiety Disorder:

Take the number of capsules as instructed by your doctor.

The dose, which has been adjusted for you and your condition, will generally be between

150 mg and 600 mg each day.

Your doctor will tell you to take <Product name> either twice or three times a day. For twice

a day take <Product name> once in the morning and once in the evening, at about the same

time each day. For three times a day take <Product name> once in the morning, once in

the afternoon and once in the evening, at about the same time each day.

If you have the impression that the effect of <Product name> is too strong or too weak, talk to

your doctor or pharmacist.

If you are an elderly patient (over 65 years of age), you should take <Product name> normally

except if you have problems with your kidneys.

Your doctor may prescribe a different dosing schedule and/or dose if you have problems with

your kidneys.

Swallow the capsule whole with water.

Continue taking <Product name> until your doctor tells you to stop.

If you take more <Product name> than you should

Call your doctor or go to the nearest hospital emergency unit immediately. Take your box of

<Product name> capsules with you. You may feel sleepy, confused, agitated, or restless as a

result of taking more <Product name> than you should. Fits have also been reported.

If you forget to take <Product name>

It is important to take your <Product name> capsules regularly at the same time each day. If

you forget to take a dose, take it as soon as you remember unless it is time for your next dose.

In that case, just carry on with the next dose as normal. Do not take a double dose to make up

for a forgotten dose.

If you stop taking <Product name>

Do not stop taking <Product name> unless your doctor tells you to. If your treatment is stopped

it should be done gradually over a minimum of 1 week.

After stopping long and short-term <Product name> treatment, you need to know that you may

experience certain side effects. These include trouble sleeping, headache, nausea, feeling

anxious, diarrhoea, flu-like symptoms, convulsions, nervousness, depression, pain, sweating,

and dizziness. These symptoms may occur more commonly or severely if you have been

taking <Product name> for a longer period of time.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience swollen face or tongue or if your skin turns red and starts to blister or

peel you should seek immediate medical advice.

Very common (may affect more than 1 in 10 people):

dizziness, drowsiness, headache

Common (may affect up to 1 in 10 people):

increased appetite

feeling of elation, confusion, disorientation, decrease in sexual interest, irritability

disturbance in attention, clumsiness, memory impairment, loss of memory, tremor, difficulty

with speaking, tingling feeling, numbness, sedation, lethargy, insomnia, fatigue, feeling

abnormal

blurred vision, double vision

vertigo, problems with balance, fall

dry mouth, constipation, vomiting, flatulence, diarrhoea, nausea, swollen abdomen

difficulties with erection

swelling of the body including extremities

feeling drunk, abnormal style of walking

weight gain

muscle cramp, joint pain, back pain, pain in limb

sore throat

Uncommon (may affect up to 1 in 100 people):

loss of appetite, weight loss, low blood sugar, high blood sugar

change in perception of self, restlessness, depression, agitation, mood swings, difficulty

finding words, hallucinations, abnormal dreams, panic attack, apathy, aggression, elevated

mood, mental impairment, difficulty with thinking, increase in sexual interest, problems with

sexual functioning including inability to achieve a sexual climax, delayed ejaculation

changes in eyesight, unusual eye movement, changes in vision including tunnel vision,

flashes of light, jerky movements, reduced reflexes, increased activity, dizziness on

standing, sensitive skin, loss of taste, burning sensation, tremor on movement, decreased

consciousness, loss of consciousness, fainting, increased sensitivity to noise, feeling unwell

dry eyes, eye swelling, eye pain, weak eyes, watery eyes, eye irritation

heart rhythm disturbances, increased heart rate, low blood pressure, high blood pressure,

changes in heart beat, heart failure

flushing, hot flushes

difficulty breathing, dry nose, nasal congestion

increased saliva production, heartburn, numb around mouth

sweating, rash, chills, fever

muscle twitching, joint swelling, muscle stiffness, pain including muscle pain, neck pain

breast pain

difficulty with or painful urination, incontinence

weakness, thirst, chest tightness

changes in blood and liver test results (blood creatinine phosphokinase increased, alanine

amino

transferase

increased,

aspartate

aminotransferase

increased,

platelet

count

decreased, neutropenia, increase in blood creatinine, decrease in blood potassium)

hypersensitivity, swollen face, itchiness, hives, runny nose, nose bleed, cough, snoring

painful menstrual periods

coldness of hands and feet

Rare (may affect up to 1 in 1,000 people):

abnormal sense of smell, swinging vision, altered perception of depth, visual brightness,

vision loss

dilated pupils, crossed eyes

cold sweat, tightness of the throat, swollen tongue

inflammation of the pancreas

difficulty in swallowing

slow or reduced movement of the body

difficulty with writing properly

increased fluid in the abdomen

fluid in the lungs

convulsions

changes in the recording of electrical changes (ECG) in the heart which correspond to heart

rhythm disturbances

muscle damage

breast discharge, abnormal breast growth, breast growth in males

interrupted menstrual periods

kidney failure, reduced urine volume, urinary retention

decrease in white blood cell count

inappropriate behaviour

allergic reactions (which may include difficulty breathing, inflammation of the eyes

(keratitis) and a serious skin reaction characterised by rash, blisters, peeling skin and

pain)

jaundice (yellowing of the skin and eyes)

Very rare: may affect up to 1 in 10,000 people

liver failure

hepatitis (inflammation of the liver)

Certain side effects may be more common, such as sleepiness, because patients with spinal

cord injury may be taking other medicines to treat, for example, pain or spasticity, that have

similar side effects to pregabalin and the severity of these effects may be increased when

taken together.

The following adverse reaction has been reported in the post-marketing experience: Trouble

breathing, shallow breaths.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via the national reporting

system listed in Appendix V. By reporting side effects you can help provide more information

on the safety of this medicine.

5. How to store <Product name>

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after

EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist

how to throw away medicines you no longer use. These measures will help protect the

environment.

6. Contents of the pack and other information

What <Product name> contains

The active substance is pregabalin. Each hard capsule contains either 25 mg, 50 mg,

75 mg, 100 mg, 150 mg, 200 mg, 225 mg or 300 mg pregabalin.

The other ingredients are: lactose monohydrate, starch, pregelatinised (maize), talc,

gelatine, titanium dioxide (E171). The 75, 100, 200, 225 and 300 mg capsules also

contain red iron oxide (E172). 50, 225 mg only: Shellac, Iron oxide black (E172),

Propylene Glycol

What <Product name> looks like and contents of the pack

25 mg capsules

White capsules, hard (approximately 14 mm).

50 mg capsules

White capsules, hard (approximately 16 mm). The body is marked with a

black circular line.

75 mg capsules

White and orange capsules, hard (approximately 14 mm).

100 mg capsules

Orange capsules, hard (approximately 16 mm).

150 mg capsules

White capsules, hard (approximately 18 mm).

200 mg capsules

Light orange capsules, hard (approximately 19 mm).

225 mg capsules

White and light orange capsules, hard (approximately 19 mm). The body

is marked with a black circular line.

300 mg capsules

White and orange capsules, hard (approximately 22 mm).

The following pack sizes are available:

<Product name> 25 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 28, 30, 56, 60, 70, 84, 100, 200

and 210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 28 x 1, 30 x 1,

56 x 1, 60 x 1, 70 x 1, 84 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<Product name> 50 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 28, 30, 56, 60, 84, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 28 x 1, 30 x 1,

56 x 1, 60 x 1, 84 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<Product name> 75 mg

Blisters made of PVC with an aluminium foil backing: 14, 14 (sample), 28, 30, 56, 60, 70,

100, 200 and 210 capsules.

Unit-dose blisters sizes made of PVC with an aluminium foil backing: 14 x 1, 14 x 1 (sample),

28 x 1, 30 x 1, 56 x 1, 60 x 1, 70 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<

Product name> 100 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 30, 56, 60, 84, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 30 x 1, 56 x 1,

60 x 1, 84 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<Product name> 150 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 28, 30, 56, 60, 70, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 28 x 1, 30 x 1,

56 x 1, 60 x 1, 70 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

Product name> 200 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 30, 56, 60, 84, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 30 x 1, 56 x 1,

60 x 1, 84 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<Product name> 225 mg

Blisters made of PVC with an aluminium foil backing: 14, 28, 30, 56, 60, 70, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 28 x 1, 30 x 1, 56 x 1,

60 x 1, 70 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

<Product name> 300 mg

Blisters made of PVC with an aluminium foil backing: 14, 21, 28, 30, 56, 60, 70, 100, 200 and

210 capsules.

Unit-dose blisters made of PVC with an aluminium foil backing: 14 x 1, 21 x 1, 28 x 1, 30 x 1,

56 x 1, 60 x 1, 70 x 1, 100 x 1, 200 x 1 and 210 x 1 capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

<[To be completed nationally]>

This medicinal product is authorised in the Member States of the EEA under the

following names:

<[To be completed nationally]>

This leaflet was last revised in 2021-06-09.

Läs hela dokumentet

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Lyribastad 25 mg capsules, hard

Lyribastad 50 mg capsules, hard

Lyribastad 75 mg capsules, hard

Lyribastad 100 mg capsules, hard

Lyribastad 150 mg capsules, hard

Lyribastad 200 mg capsules, hard

Lyribastad 225 mg capsules, hard

Lyribastad 300 mg capsules, hard

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule, hard contains 25 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 35.0 mg of lactose monohydrate.

Each capsule, hard contains 50 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 70.0 mg of lactose monohydrate.

Each capsule, hard contains 75 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 8.25 mg of lactose monohydrate.

Each capsule, hard contains 100 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 11.00 mg of lactose monohydrate.

Each capsule, hard contains 150 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 16.5 mg of lactose monohydrate.

Each capsule, hard contains 200 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 22.00 mg of lactose monohydrate.

Each capsule, hard contains 225 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 24.75 mg of lactose monohydrate.

Each capsule, hard contains 300 mg of pregabalin.

Excipient with known effect

Each capsule, hard contains 33.00 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Capsule, hard.

The 25 mg capsule is a white capsule, size 4 (approximately 14 mm).

The 50 mg capsule is a white capsule, size 3(approximately 16 mm). The body is marked with

a black circular line.

The 75 mg capsule is a white and orange capsule, size 4 (approximately 14 mm).

The 100 mg capsule is an orange capsule, size 3 (approximately 16 mm).

The 150 mg capsule is a white capsule, size 2 (approximately 18 mm).

The 200 mg capsule is a light orange capsule, size 1(approximately 19 mm).

The 225 mg capsule is a white and light orange capsule, size 1 (approximately 19 mm). The

body is marked with a black circular line.

The 300 mg capsule is a white and orange capsule, size 0 (approximately 22 mm).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Neuropathic pain

<Product name> is indicated for the treatment of peripheral and central neuropathic pain in

adults.

Epilepsy

<Product name> is indicated as adjunctive therapy in adults with partial seizures with or without

secondary generalisation.

Generalised Anxiety Disorder

<Product name> is indicated for the treatment of Generalised Anxiety Disorder (GAD) in adults.

4.2 Posology and method of administration

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 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 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 mg per day given as two 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 accordance with current clinical practice, if pregabalin has to be discontinued it is

recommended this should be done gradually over a minimum of 1 week independent of the

indication (see sections 4.4 and 4.8).

Renal impairment

Pregabalin

eliminated

from

systemic

circulation

primarily

renal

excretion

unchanged drug. As pregabalin clearance is directly proportional to creatinine clearance (see

section 5.2), dose reduction in patients with compromised renal function must be individualised

according to creatinine clearance (CLcr), as indicated in Table 1 determined using the following

formula:

(ml/min) =

1.23 ×

140 –age

years

x weight

serum creatinine

µmol/l

(x 0.85 for female patients)

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 given immediately

following every 4 hour haemodialysis treatment (see Table 1).

Table 1. Pregabalin dose adjustment based on renal function

Creatinine

clearance (CL

(ml/min)

Total pregabalin daily dose*

Dose regimen

Starting dose

(mg/day)

Maximum dose

(mg/day)

≥ 60

BID or TID

≥ 30 - < 60

BID or TID

≥ 15 - < 30

25 – 50**

Once Daily or BID

< 15

25**

Once Daily

Supplementary dosage following haemodialysis (mg)

25**

Single dose

TID = Three divided doses

BID = Two divided doses

Total daily dose (mg/day) should be divided as indicated by dose regimen to provide

mg/dose

<[For member states where 25 mg strength is not registered:]>

<**

There is no marketing authorisation for <Product name> 25 mg capsules, this presentation

may be available from other pregabalin products.>

Supplementary dose is a single additional dose

Hepatic impairment

No dose adjustment is required for patients with hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of pregabalin in children below the age of 12 years and in adolescents

(12-17 years of age) have not been established. Currently available data are described in

sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

Elderly

Elderly patients may require a dose reduction of pregabalin due to a decreased renal function

(see section 5.2).

Method of administration

<Product name> may be taken with or without food.

<Product name> is for oral use only.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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 post-marketing experience of hypersensitivity reactions,

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 loss of consciousness, confusion and mental impairment.

Therefore, patients should be advised to exercise caution until they are familiar with the

potential effects of the medicinal product.

Vision-related effects

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. In the clinical studies where ophthalmologic testing was conducted, the

incidence 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 (see section 5.1).

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 of pregabalin may result in resolution or 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

short-term

long-term

treatment

with

pregabalin

withdrawal

symptoms have been observed in some patients. The following events have been mentioned:

insomnia, headache, nausea, anxiety, diarrhoea, 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 discontinuation of long-term treatment of pregabalin, data suggest that the

incidence and severity of withdrawal symptoms may be dose-related.

Congestive heart failure

There have been post-marketing reports of congestive heart failure in some patients receiving

pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients

during pregabalin treatment for a neuropathic indication. Pregabalin should be used with

caution in these patients. Discontinuation of pregabalin may resolve the reaction.

Treatment of central neuropathic pain due to 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. anti-spasticity agents) needed for this condition. This should be considered

when prescribing pregabalin in this condition.

Respiratory depression

There have been reports of severe respiratory depression in relation to pregabalin use.

Patients with compromised respiratory function, respiratory or neurological disease, renal

impairment, concomitant use of CNS depressants and the elderly may be at higher risk of

experiencing this severe adverse reaction. Dose adjustments may be necessary in these

patients (see section 4.2).

Suicidal ideation and behaviour

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic

agents in several indications. A meta-analysis of randomised placebo controlled studies of

antiepileptic 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 pregabalin.

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.

Reduced lower gastrointestinal tract function

There are post-marketing reports of events related to reduced lower gastrointestinal tract

function

(e.g.

intestinal

obstruction,

paralytic

ileus,

constipation)

when

pregabalin

co-administered with medications that have the potential to produce constipation, such as

opioid analgesics. When pregabalin and opioids will be used in combination, measures to

prevent constipation may be considered (especially in female patients and elderly).

Concomitant use with opioids

Caution is advised when prescribing pregabalin concomitantly with opioids due to risk of CNS

depression (see section 4.5). In a case-control study of opioid users, those patients who took

pregabalin concomitantly with an opioid had an increased risk for opioid-related death

compared to opioid use alone (adjusted odds ratio [aOR], 1.68 [95 % CI, 1.19 – 2.36]). This

increased risk was observed at low doses of pregabalin (≤ 300 mg, aOR 1.52 [95 % CI, 1.04

– 2.22]) and there was a trend for a greater risk at high doses of pregabalin (> 300 mg, aOR

2.51 [95 % CI 1.24 – 5.06]).

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, drug-

seeking behaviour have been reported).

Encephalopathy

Cases of encephalopathy have been reported, mostly in patients with underlying conditions

that may precipitate encephalopathy.

Lactose intolerance

This medicinal product contains lactose. Patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take

this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Since pregabalin is predominantly excreted 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 antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no

clinically significant effect on pregabalin clearance.

Oral contraceptives, norethisterone and/or ethinyl oestradiol

Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl

oestradiol does not influence the steady-state pharmacokinetics of either substance.

Central nervous system influencing medical products

Pregabalin may potentiate the effects of ethanol and lorazepam.

In the post-marketing experience, there are reports of respiratory failure, coma and deaths in

patients taking pregabalin and opioids and/or other central nervous system (CNS) depressant

medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross

motor function caused by oxycodone.

Interactions and the elderly

No specific pharmacodynamic interaction studies were conducted in elderly volunteers.

Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential/contraception in males and females

As the potential risk for humans is unknown, effective contraception must be used in women

of child bearing potential.

Pregnancy

There are no adequate data from the use of pregabalin in pregnant women. Studies in animals

have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Pregabalin should not be used during pregnancy unless clearly necessary (if the benefit to the

mother clearly outweighs the potential risk to the foetus).

Breast-feeding

Pregabalin is excreted into human milk (see section 5.2). The effect of pregabalin on

newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding

or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the

child and the benefit of therapy for the woman.

Fertility

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 (see section 5.3).

4.7 Effects on ability to drive and use machines

Pregabalin may have minor or moderate influence on the ability to drive and use machines.

Pregabalin 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.

4.8 Undesirable effects

The pregabalin clinical programme involved over 8,900 patients exposed to pregabalin, of

whom over 5,600 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 resulting in discontinuation from pregabalin treatment groups were

dizziness and somnolence.

In table 2 below all adverse reactions, 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 (see

section 4.4).

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

below.

Table 2. Pregabalin Adverse Drug Reactions

System Organ Class

Adverse drug reactions

Infections and infestations

Common

Nasopharyngitis

Blood and lymphatic system disorders

Uncommon

Neutropenia

Immune system disorders

Uncommon

Rare

Hypersensitivity

Angioedema, allergic reaction

Metabolism and nutrition disorders

Common

Uncommon

Appetite increased

Anorexia, hypoglycaemia

Psychiatric disorders

Common

Uncommon

Euphoric mood, confusion, irritability,

disorientation, insomnia, libido decreased

Hallucination, panic attack, restlessness,

agitation, depression, depressed mood, elevated

Rare

mood, aggression, mood swings,

depersonalisation, word finding difficulty,

abnormal dreams, libido increased, anorgasmia,

apathy

Disinhibition

Nervous system disorders

Very Common

Common

Uncommon

Rare

Dizziness, somnolence, headache

Ataxia, coordination abnormal, tremor,

dysarthria, amnesia, memory impairment,

disturbance in attention, paraesthesia,

hypoaesthesia, sedation, balance disorder,

lethargy

Syncope, stupor, myoclonus, loss of

consciousness, psychomotor hyperactivity,

dyskinesia, dizziness postural, intention tremor,

nystagmus, cognitive disorder, mental

impairment, speech disorder, hyporeflexia,

hyperaesthesia, burning sensation, ageusia,

malaise

Convulsions, parosmia, hypokinesia, dysgraphia

Eye disorders

Common

Uncommon

Rare

Vision blurred, diplopia

Peripheral vision loss, visual disturbance, eye

swelling, visual field defect, visual acuity

reduced, eye pain, asthenopia, photopsia, dry

eye, lacrimation increased, eye irritation

Vision loss, keratitis, oscillopsia, altered visual

depth perception, mydriasis, strabismus, visual

brightness

Ear and labyrinth disorders

Common

Uncommon

Vertigo

Hyperacusis

Cardiac disorders

Uncommon

Rare

Tachycardia, atrioventricular block first degree,

sinus bradycardia, congestive heart failure

QT prolongation, sinus tachycardia, sinus

arrhythmia

Vascular disorders

Uncommon

Hypotension, hypertension, hot flushes, flushing,

peripheral coldness

Respiratory, thoracic and mediastinal

disorders

Uncommon

Rare

Not known

Dyspnoea, epistaxis, cough, nasal congestion,

rhinitis, snoring, nasal dryness

Pulmonary oedema, throat tightness

Respiratory depression

Gastrointestinal disorders

Common

Uncommon

Vomiting, nausea, constipation, diarrhoea,

flatulence, abdominal distension, dry mouth

Gastrooesophageal reflux disease, salivary

hypersecretion, hypoaesthesia oral

Rare

Ascites, pancreatitis, swollen tongue, dysphagia

Hepatobiliary disorders

Uncommon

Rare

Very rare

Elevated liver enzymes *

Jaundice

Hepatic failure, hepatitis

Skin and subcutaneous tissue disorders

Uncommon

Rare

Rash papular, urticaria, hyperhidrosis, pruritus

Stevens-Johnson syndrome, cold sweat

Musculoskeletal and connective tissue

disorders

Common

Uncommon

Rare

Muscle cramp, arthralgia, back pain, pain in

limb, cervical spasm

Joint swelling, myalgia, muscle twitching, neck

pain, muscle stiffness

Rhabdomyolysis

Renal and urinary disorders

Uncommon

Rare

Urinary incontinence, dysuria

Renal failure, oliguria, urinary retention

Reproductive system and breast disorders

Common

Uncommon

Rare

Erectile dysfunction

Sexual dysfunction, ejaculation delayed,

dysmenorrhoea, breast pain

Amenorrhoea, breast discharge, breast

enlargement, gynaecomastia

General disorders and administration site

conditions

Common

Uncommon

Oedema peripheral, oedema, gait abnormal, fall,

feeling drunk, feeling abnormal, fatigue

Generalised oedema, face oedema, chest

tightness, pain, pyrexia, thirst, chills, asthenia

Investigations

Common

Uncommon

Rare

Weight increased

Blood creatine phosphokinase increased, blood

glucose increased, platelet count decreased,

blood creatinine increased, blood potassium

decreased, weight decreased

White blood cell count decreased

* Alanine aminotransferase increased (ALT) and aspartate aminotransferase increased (AST).

After

discontinuation

short-term

long-term

treatment

with

pregabalin

withdrawal

symptoms

have

been

observed

some

patients.

following

reactions

have

been

mentioned: insomnia, headache, nausea, anxiety, diarrhoea, flu syndrome, convulsions,

nervousness,

depression,

pain,

hyperhidrosis

dizziness,

suggestive

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.

Paediatric population

The pregabalin safety profile observed in five paediatric studies in patients with partial seizures

with or without secondary generalisation (12-week efficacy and safety study in patients 4 to

16 years of age, n=295; 14-day efficacy and safety study in patients 1 month to younger than

4 years of age, n=175; pharmacokinetic and tolerability study, n=65; and two 1 year open label

follow on safety studies, n=54 and n=431) was similar to that observed in the adult studies of

patients with epilepsy. The most common adverse events observed in the 12-week study with

pregabalin treatment were somnolence, pyrexia, upper respiratory tract infection, increased

appetite, weight increased, and nasopharyngitis. The most common adverse events observed

in the 14-day study with pregabalin treatment were somnolence, upper respiratory tract

infection, and pyrexia (see sections 4.2, 5.1 and 5.2).

Reporting of suspected adverse reactions

Reporting

suspected

adverse

reactions

after

authorisation

medicinal

product

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 national

reporting system listed in Appendix V.

4.9 Overdose

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.

Seizures were also reported.

In rare occasions, cases of coma have been reported.

Treatment of pregabalin overdose should include general supportive measures and may

include haemodialysis if necessary (see section 4.2 Table 1).

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiepileptics, other antiepileptics, ATC code: N03AX16

active

substance,

pregabalin,

gamma-aminobutyric

acid

analogue

[(S)-3-(aminomethyl)-5-methylhexanoic acid].

Mechanism of action

Pregabalin binds to an auxiliary subunit (α

-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, post 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 neuropathic 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 % of 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 the

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 BID

or 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 1.

Paediatric population

The efficacy and safety of pregabalin as adjunctive treatment for epilepsy in paediatric patients

below the age of 12 and adolescents has not been established. The adverse events observed

in a pharmacokinetic and tolerability study that enrolled patients from 3 months to 16 years of

age (n=65) with partial onset seizures were similar to those observed in adults. Results of a

12-week placebo controlled study of 295 paediatric patients aged 4 to 16 years and a 14-day

placebo-controlled study of 175 paediatric patients aged 1 month to younger than 4 years of

age performed to evaluate the efficacy and safety of pregabalin as adjunctive therapy for the

treatment of partial onset seizures and two 1 year open label safety studies in 54 and 431

paediatric patients respectively from 3 months to 16 years of age with epilepsy indicate that

the adverse events of pyrexia and upper respiratory infections were observed more frequently

than in adult studies of patients with epilepsy (see sections 4.2, 4.8 and 5.2).

In the 12-week placebo-controlled study, paediatric patients (4 to 16 years of age) were

assigned to pregabalin 2.5 mg/kg/day (maximum, 150 mg/day), pregabalin 10 mg/kg/day

(maximum, 600 mg/day), or placebo. The percentage of subjects with at least a 50 % reduction

in partial onset seizures as compared to baseline was 40.6 % of subjects treated with

pregabalin

10 mg/kg/day

(p=0.0068

versus

placebo),

29.1 %

subjects

treated

with

pregabalin 2.5 mg/kg/day (p=0.2600 versus placebo) and 22.6 % of those receiving placebo.

In the 14-day placebo-controlled study, paediatric patients (1 month to younger than 4 years

of age) were assigned to pregabalin 7 mg/kg/day, pregabalin 14 mg/kg/day, or placebo.

Median 24-hour seizure frequencies at baseline and at the final visit were 4.7 and 3.8 for

pregabalin 7 mg/kg/day, 5.4 and 1.4 for pregabalin 14 mg/kg/day, and 2.9 and 2.3 for placebo,

respectively. Pregabalin 14 mg/kg/day significantly reduced the log-transformed partial onset

seizure

frequency

versus

placebo

(p=0.0223);

pregabalin

7 mg/kg/day

show

improvement relative to placebo.

Monotherapy (newly diagnosed patients)

Pregabalin has been studied in 1 controlled clinical trial of 56 week duration with BID dosing.

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.

Generalised 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. Ophthalmologic testing (including visual acuity testing, formal visual field

testing and dilated funduscopic examination) was conducted in over 3,600 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 pregabalin-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.

5.2 Pharmacokinetic properties

Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with

epilepsy receiving antiepileptic 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 of 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 C

by approximately

25-30 % and a delay in t

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 0.56 l/kg. Pregabalin is not bound to plasma proteins.

Biotransformation

Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled

pregabalin, approximately 98 % of the radioactivity recovered in the 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

eliminated

from

systemic

circulation

primarily

renal

excretion

unchanged drug. Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma

clearance and renal clearance are directly proportional to creatinine clearance (see section 5.2

Renal impairment). Dose adjustment in patients with reduced renal function or undergoing

haemodialysis is necessary (see section 4.2 Table 1).

Linearity/non-linearity

Pregabalin pharmacokinetics are linear over the recommended daily dose range. Inter-subject

pharmacokinetic variability for pregabalin is low (< 20 %). Multiple dose pharmacokinetics are

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 a 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 (see section 4.2 Table 1).

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 as

unchanged drug in the urine, impaired liver function would not be expected to significantly alter

pregabalin plasma concentrations.

Paediatric population

Pregabalin pharmacokinetics were evaluated in paediatric patients with epilepsy (age groups:

1 to 23 months, 2 to 6 years, 7 to 11 years and 12 to 16 years) at dose levels of 2.5, 5, 10 and

15 mg/kg/day in a pharmacokinetic and tolerability study.

After oral administration of pregabalin in paediatric patients in the fasted state, in general, time

to reach peak plasma concentration was similar across the entire age group and occurred

0.5 hours to 2 hours postdose.

Pregabalin C

and AUC parameters increased in a linear manner with increasing dose within

each age group. The AUC was lower by 30 % in paediatric patients below a weight of 30 kg

due to an increased body weight adjusted clearance of 43 % for these patients in comparison

to patients weighing ≥ 30 kg.

Pregabalin terminal half-life averaged about 3 to 4 hours in paediatric patients up to 6 years of

age, and 4 to 6 hours in those 7 years of age and older.

Population pharmacokinetic analysis showed that creatinine clearance was a significant

covariate of pregabalin oral clearance, body weight was a significant covariate of pregabalin

apparent oral volume of distribution, and these relationships were similar in paediatric and

adult patients.

Pregabalin pharmacokinetics in patients younger than 3 months old have not been studied

(see sections 4.2, 4.8 and 5.1).

Elderly

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 (see section 4.2 Table 1).

Breast-feeding mothers

The pharmacokinetics of 150 mg pregabalin given every 12 hours (300 mg daily dose) was

evaluated in 10 lactating women who were at least 12 weeks postpartum. Lactation had little

to no influence on pregabalin pharmacokinetics. Pregabalin was excreted into breast milk with

average steady-state concentrations approximately 76 % of those in maternal plasma. The

estimated infant dose from breast milk (assuming mean milk consumption of 150 ml/kg/day)

of women receiving 300 mg/day or the maximum dose of 600 mg/day would be 0.31 or

0.62 mg/kg/day, respectively. These estimated doses are approximately 7 % of the total daily

maternal dose on a mg/kg basis.

5.3 Preclinical safety data

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 exposures ≥ 5 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

occurred

only

exposures

sufficiently

excess

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 tumours

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 tumours was

found at exposures similar to the mean human exposure, but an increased incidence of

haemangiosarcoma was observed at higher exposures. The non-genotoxic mechanism of

pregabalin-induced tumour formation in mice involves 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.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsules content

Lactose Monohydrate

Starch, pregelatinised (maize)

Talc

Capsules shell

25 mg

Body and cap: Gelatin, Titanium dioxide (E171)

50 mg

Body and cap: Gelatin, Titanium dioxide (E171)

Printing ink: Shellac, Iron oxide black (E172), Propylene Glycol

75 mg

Body: Gelatin, Titanium dioxide (E171)

Cap: Gelatin, Titanium dioxide (E171), Red Iron Oxide (E172)

100 mg

Body and cap: Gelatin, Titanium dioxide (E171), Red Iron Oxide (E172)

150 mg

Body and cap: Gelatin, Titanium dioxide (E171)

200 mg

Body and cap: Gelatin, Titanium dioxide (E171), Red Iron Oxide (E172)

225 mg

Body: Gelatin, Titanium dioxide (E171)

Cap: Gelatin, Titanium dioxide (E171), Red Iron Oxide (E172)

Printing ink: Shellac, Iron oxide black (E172), Propylene Glycol

300 mg

Body: Gelatin, Titanium dioxide (E171)

Cap: Gelatin, Titanium dioxide (E171), Red Iron Oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

6.5 Nature and contents of container

25 mg

Aluminium/PVC blisters containing 14, 21, 28, 30, 56, 60, 70, 84, 100, 200 or 210 capsules,

hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 70

x 1, 84 x 1, 100 x 1, 200 x 1 or 210 x 1 capsules, hard.

50 mg

Aluminium/PVC blisters containing 14, 21, 28, 30, 56, 60, 84, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 84

x 1, 100 x 1, 200 x 1 or 210 x 1 capsules, hard.

75 mg

Aluminium/PVC blisters containing 14, 14 (sample), 28, 30, 56, 60, 70, 100, 200 or 210

capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 14 x 1 (sample), 28 x 1, 30 x 1, 56 x 1, 60

x 1, 70 x 1, 100 x 1, 200 x 1 or 210 x 1 capsules, hard.

100 mg

Aluminium/PVC blisters containing 14, 21, 30, 56, 60, 84, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 30 x 1, 56 x 1, 60 x 1, 84 x 1, 100

x 1, 200 x 1 or 210 x 1 capsules, hard.

150 mg

Aluminium/PVC blisters containing 14, 21, 28, 30, 56, 60, 70, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 70

x 1, 100 x 1, 200 x 1 or 210 x 1 capsules, hard.

200 mg

Aluminium/PVC blisters containing 14, 21, 30, 56, 60, 84, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 30 x 1, 56 x 1, 60 x 1, 84 x 1, 100

x 1, 200 x 1 or 210 x 1 capsules, hard.

225 mg

Aluminium/PVC blisters containing 14, 28, 30, 56, 60, 70, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 70 x 1, 100

x 1, 200 x 1 or 210 x 1 capsules, hard.

300 mg

Aluminium/PVC blisters containing 14, 21, 28, 30, 56, 60, 70, 100, 200 or 210 capsules, hard.

Aluminium/PVC unit-dose blisters containing 14 x 1, 21 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 70

x 1, 100 x 1, 200 x 1 or 210 x 1 capsules, hard.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

<[To be completed nationally]>

8. MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<[To be completed nationally]>

10. DATE OF REVISION OF THE TEXT

2021-06-09

Liknande Produkter

Sök varningar relaterade till denna produkt

Visa dokumenthistorik

Dela den här informationen