Pregabalin 75mg capsules

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Pregabalin
Available from:
Mylan
ATC code:
N03AX16
INN (International Name):
Pregabalin
Dosage:
75mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04080100; GTIN: 5016695006352

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Package leaflet: Information for the user

Pregabalin Mylan 25 mg hard capsules

Pregabalin Mylan 50 mg hard capsules

Pregabalin Mylan 75 mg hard capsules

Pregabalin Mylan 100 mg hard capsules

Pregabalin Mylan 150 mg hard capsules

Pregabalin Mylan 200 mg hard capsules

Pregabalin Mylan 225 mg hard capsules

Pregabalin Mylan 300 mg hard capsules

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 Pregabalin Mylan is and what it is used for

What you need to know before you take Pregabalin Mylan

How to take Pregabalin Mylan

Possible side effects

How to store Pregabalin Mylan

Contents of the pack and other information

1.

What Pregabalin Mylan is and what it is used for

Pregabalin Mylan contains the active substance pregabalin which belongs to a group of medicines

used to treat epilepsy, neuropathic pain and Generalised Anxiety Disorder (GAD) in adults.

Peripheral and central neuropathic pain:

Pregabalin Mylan 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:

Pregabalin Mylan is used to treat a certain form of epilepsy (partial seizures with or without

secondary generalisation) in adults. Your doctor will prescribe Pregabalin Mylan for you to help treat

your epilepsy when your current treatment is not controlling your condition. You should take

Pregabalin Mylan in addition to your current treatment. Pregabalin Mylan is not intended to be used

alone, but should always be used in combination with other anti-epileptic treatment.

Generalised Anxiety Disorder:

Pregabalin Mylan 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 Pregabalin Mylan

Do not take Pregabalin Mylan:

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 Pregabalin Mylan.

Some patients taking Pregabalin Mylan 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.

Pregabalin Mylan 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.

Pregabalin Mylan 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 Pregabalin Mylan; 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 Pregabalin Mylan. If

while taking Pregabalin Mylan 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 Pregabalin Mylan have

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

immediately contact your doctor.

When Pregabalin Mylan 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 Pregabalin Mylan or shortly after

stopping Pregabalin Mylan. If you experience a convulsion, contact your doctor immediately.

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

taking Pregabalin Mylan when they have other conditions. Tell your doctor if you have a

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

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 Pregabalin Mylan

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

medicines.

Pregabalin Mylan and certain other medicines may influence each other (interaction). When taken

with certain other medicines, Pregabalin Mylan may potentiate the side effects seen with these

medicines, including respiratory failure and coma. The degree of dizziness, sleepiness and decreased

concentration may be increased if Pregabalin Mylan is taken together with medicinal products

containing:

Oxycodone – (used as a pain-killer)

Lorazepam – (used for treating anxiety)

Alcohol

Pregabalin Mylan may be taken with oral contraceptives.

Pregabalin Mylan with food, drink and alcohol

Pregabalin Mylan capsules may be taken with or without food.

It is advised not to drink alcohol while taking Pregabalin Mylan.

Pregnancy and breast-feeding

Pregabalin Mylan 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

Pregabalin Mylan 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.

3.

How to take Pregabalin Mylan

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

or pharmacist if you are not sure.

Your doctor will determine what dose is appropriate for you.

Pregabalin Mylan 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 Pregabalin Mylan either twice or three times a day. For twice

a day take Pregabalin Mylan once in the morning and once in the evening, at about the same

time each day. For three times a day take Pregabalin Mylan 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 Pregabalin Mylan is too strong or too weak, talk to your

doctor or pharmacist.

If you are an older patient (over 65 years of age), you should take Pregabalin Mylan 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 Pregabalin Mylan until your doctor tells you to stop.

If you take more Pregabalin Mylan than you should

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

Pregabalin Mylan capsules with you. You may feel sleepy, confused, agitated, or restless as a result of

taking more Pregabalin Mylan than you should. Fits have also been reported.

If you forget to take Pregabalin Mylan

It is important to take your Pregabalin Mylan 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 Pregabalin Mylan

Do not stop taking Pregabalin Mylan 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 Pregabalin Mylan treatment, you need to know that you may

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

diarrhoea, flulike symptoms, convulsions, nervousness, depression, pain, sweating, and dizziness.

These symptoms may occur more commonly or severely if you have been taking Pregabalin Mylan

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.

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 attacks, 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

aminotransferase 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, cross 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 characterized by rash, blisters, peeling skin and pain)

Jaundice (yellowing of the skin and eyes).

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

Liver failure.

Hepatitis (inflammation of the liver).

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.

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.

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:

United Kingdom

Yellow Card Scheme Website:

www.mhra.gov.uk/yellowcard

Or search for MHRA Yellow Card in the Google Play or

Apple App Store.

Ireland

HPRA Pharmacovigilance, Earlsfort Terrace,

IRL – Dublin 2;

Tel: +353 1 6764971; Fax: +353 1 6762517

Website: www.hpra.ie;

E-mail: medsafety@hpra.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Pregabalin Mylan

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.

Blister: Store in the original package in order to protect from moisture.

Bottle: Keep the bottle tightly closed in order to protect from moisture.

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 Pregabalin Mylan 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

of pregabalin.

The other ingredients are: hydroxylpropylcellulose, maize starch, talc, gelatin, titanium dioxide

(E171), sodium laurilsulfate, black ink (which contains shellac, black iron oxide (E172), macrogol,

potassium hydroxide and concentrated ammonia solution), yellow iron oxide (E172) and erythrosine

(E127).

What Pregabalin Mylan looks like and contents of the pack

Hard capsule.

Pregabalin Mylan 25 mg

hard capsule

Light peach opaque cap and white opaque body, hard-shell gelatin

capsule filled with white to off-white powder. The capsule is axially

printed with

MYLAN

over

PB25

in black ink on cap and body.

Available in blister packs containing 14, 21, 56, 84, 100 capsules and

in perforated unit dose blister packs containing 56 x 1, 84 x 1, 100 x

1 capsules.

Pregabalin Mylan 50 mg

hard capsule

Dark peach opaque cap and white opaque body, hard-shell gelatin

capsule filled with white to off-white powder. The capsule is axially

printed with

MYLAN

over

PB50

in black ink on cap and body.

Available in blister packs containing 14, 21, 56, 84, 100 capsules and

in perforated unit dose blister packs containing 84 x 1, 100 x 1

capsules.

Pregabalin Mylan 75 mg

hard capsule

Light peach opaque cap and light peach opaque body, hard-shell

gelatin capsule filled with white to off-white powder. The capsule is

axially printed with

MYLAN

over

PB75

in black ink on cap and

body.

Available in blister packs containing 14, 56, 100 capsules, in

perforated unit dose blister packs containing 14 x 1, 56 x 1, 100 x 1

capsules and in bottles containing 200 capsules.

Pregabalin Mylan

100 mg hard capsule

Dark peach opaque cap and dark peach opaque body, hard-shell

gelatin capsule filled with white to off-white powder. The capsule is

axially printed with

MYLAN

over

PB100

in black ink on cap and

body.

Available in blister packs containing 21, 84, 100 capsules and in

perforated unit dose blister packs containing 84 x 1, 100 x 1

capsules.

Pregabalin Mylan

150 mg hard capsule

Light peach opaque cap and white opaque body, hard-shell gelatin

capsule filled with white to off-white powder. The capsule is axially

printed with

MYLAN

over

PB150

in black ink on cap and body.

Available in blister packs containing 14, 56, 100 capsules, in

perforated unit dose blister packs containing 14 x 1, 56 x 1, 100 x 1

capsules and in bottles containing 200 capsules.

Pregabalin Mylan

200 mg hard capsule

Light peach opaque cap and light peach opaque body, hard-shell

gelatin capsule filled with white to off-white powder. The capsule is

axially printed with

MYLAN

over

PB200

in black ink on cap and

body.

Available in blister packs containing 21, 84, 100 capsules and in

perforated unit dose blister packs containing 84 x 1, 100 x 1

capsules.

Pregabalin Mylan

225 mg hard capsule

Dark peach opaque cap and dark peach opaque body, hard-shell

gelatin capsule filled with white to off-white powder. The capsule is

axially printed with

MYLAN

over

PB225

in black ink on cap and

body.

Available in blister packs containing 14, 56, 100 capsules and in

perforated unit dose blister packs containing 56 x 1, 100 x 1

capsules.

Pregabalin Mylan

300 mg hard capsule

Light peach opaque cap and white opaque body, hard-shell gelatin

capsule filled with white to off-white powder. The capsule is axially

printed with

MYLAN

over

PB300

in black ink on cap and body.

Available in blister packs containing 14, 56, 100 capsules, in

perforated unit dose blister packs containing 56 x 1, 100 x 1 capsules

and in bottles containing 200 capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Generics [UK] Limited,

Station Close, Potters Bar

Hertfordshire

EN6 1TL

United Kingdom

Manufacturer

Mylan Hungary Kft, Mylan utca 1, Komárom, 2900, Hungary

McDermott Laboratories Limited t/a Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange

Road, Dublin 13, Ireland

Mylan B.V., Dieselweg 25, 3752 LB Bunschoten, The Netherlands

Logiters, Logistica, Portugal, S.A., Estrada dos Arneiros, 4, Azambuja, 2050-544, Portugal

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder.

Ireland

Generics [UK] Ltd.

Tel: + 44 1707 853000

(United Kingdom)

United Kingdom

Generics [UK] Ltd

Tel: +44 1707 853000

This leaflet was last revised in May 2018.

Read the complete document

Object 1

Pregabalin Mylan 25 mg hard capsules

Summary of Product Characteristics Updated 19-Jun-2018 | Generics UK T/A Mylan

1. Name of the medicinal product

Pregabalin Mylan 25 mg hard capsules

Pregabalin Mylan 50 mg hard capsules

Pregabalin Mylan 75 mg hard capsules

Pregabalin Mylan 100 mg hard capsules

Pregabalin Mylan 150 mg hard capsules

Pregabalin Mylan 200 mg hard capsules

Pregabalin Mylan 225 mg hard capsules

Pregabalin Mylan 300 mg hard capsules

2. Qualitative and quantitative composition

Pregabalin Mylan 25 mg hard capsules

Each hard capsule contains 25 mg of pregabalin.

Pregabalin Mylan 50 mg hard capsules

Each hard capsule contains 50 mg of pregabalin.

Pregabalin Mylan 75 mg hard capsules

Each hard capsule contains 75 mg of pregabalin.

Pregabalin Mylan 100 mg hard capsules

Each hard capsule contains 100 mg of pregabalin.

Pregabalin Mylan 150 mg hard capsules

Each hard capsule contains 150 mg of pregabalin.

Pregabalin Mylan 200 mg hard capsules

Each hard capsule contains 200 mg of pregabalin.

Pregabalin Mylan 225 mg hard capsules

Each hard capsule contains 225 mg of pregabalin.

Pregabalin Mylan 300 mg hard capsules

Each hard capsule contains 300 mg of pregabalin.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Hard capsule.

Pregabalin Mylan 25 mg hard capsules

No. 4, light peach opaque cap and white opaque body, hard-shell gelatin capsule filled with white to off-

white powder. The capsule is axially printed with MYLAN over PB25 in black ink on cap and body.

Pregabalin Mylan 50 mg hard capsules

No. 3, dark peach opaque cap and white opaque body, hard-shell gelatin capsule filled with white to off-

white powder. The capsule is axially printed with MYLAN over PB50 in black ink on cap and body.

Pregabalin Mylan 75 mg hard capsules

No. 4, light peach opaque cap and light peach opaque body, hard-shell gelatin capsule filled with white to

off-white powder. The capsule is axially printed with MYLAN over PB75 in black ink on cap and body.

Pregabalin Mylan 100 mg hard capsules

No. 3, dark peach opaque cap and dark peach opaque body, hard-shell gelatin capsule filled with white to

off-white powder. The capsule is axially printed with MYLAN over PB100 in black ink on cap and body.

Pregabalin Mylan 150 mg hard capsules

No. 2, light peach opaque cap and white opaque body, hard-shell gelatin capsule filled with white to off-

white powder. The capsule is axially printed with MYLAN over PB150 in black ink on cap and body.

Pregabalin Mylan 200 mg hard capsules

No. 1, light peach opaque cap and light peach opaque body, hard-shell gelatin capsule filled with white to

off-white powder. The capsule is axially printed with MYLAN over PB200 in black ink on cap and body.

Pregabalin Mylan 225 mg hard capsules

No. 1, dark peach opaque cap and dark peach opaque body, hard-shell gelatin capsule filled with white to

off-white powder. The capsule is axially printed with MYLAN over PB225 in black ink on cap and body.

Pregabalin Mylan 300 mg hard capsules

No. 0, light peach opaque cap and white opaque body, hard-shell gelatin capsule filled with white to off-

white powder. The capsule is axially printed with MYLAN over PB300 in black ink on cap and body.

4. Clinical particulars

4.1 Therapeutic indications

Neuropathic pain

Pregabalin Mylan is indicated for the treatment of peripheral and central neuropathic pain in adults.

Epilepsy

Pregabalin Mylan is indicated as adjunctive therapy in adults with partial seizures with or without

secondary generalisation.

Generalised Anxiety Disorder

Pregabalin Mylan 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).

Special populations

Renal impairment

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as 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:

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

Once Daily

Supplementary dosage following haemodialysis (mg)

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

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 Mylan 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 section 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 patients

with renal impairment).

Method of administration

Pregabalin Mylan may be taken with or without food.

Pregabalin Mylan 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 anti-epileptic medicinal products

There are insufficient data for the withdrawal of concomitant anti-epileptic medicinal products, once

seizure control with pregabalin in the add-on situation has been reached, in order to reach monotherapy

on pregabalin.

Withdrawal symptoms

After discontinuation of short-term and long-term treatment with pregabalin, 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.

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 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 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 was 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).

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.

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 controlled clinical trials, multiple oral

doses of pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically

important effects on respiration. In the post-marketing experience, there are reports of respiratory failure

and coma in patients taking pregabalin and 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 Mylan 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 Mylan may have minor or moderate influence on the ability to drive and use machines.

Pregabalin Mylan 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

Summary of the safety profile

The pregabalin clinical programme involved over 8900 patients exposed to pregabalin, of whom over

5600 were in double-blind placebo controlled trials. The most commonly reported adverse reactions were

dizziness and somnolence. Adverse reactions were usually mild to moderate in intensity. In all controlled

studies, the discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and

5% for patients receiving placebo. The most common adverse reactions resulting in discontinuation from

pregabalin treatment groups were dizziness and somnolence.

Tabulated list of adverse reactions

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, CNC 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

Neutropaenia

Immune system disorders

Uncommon

Rare

Hypersensitivity

Angioedema, allergic reaction

Metabolism and nutrition disorders

Common

Uncommon

Appetite increased

Anorexia, hypoglycaemia

Psychiatric disorders

Common

Uncommon

Rare

Euphoric mood, confusion, irritability,

disorientation, insomnia, libido decreased

Hallucination, panic attack, restlessness, agitation,

depression, depressed mood, elevated 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

Convulsion, 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

Dyspnoea, epistaxis, cough, nasal congestion,

rhinitis, snoring, nasal dryness

Pulmonary oedema, throat tightness

Gastrointestinal disorders

Common

Uncommon

Rare

Vomiting, nausea, constipation, diarrhoea,

flatulence, abdominal distension, dry mouth

Gastrooesophageal reflux disease, salivary

hypersecretion, hypoaesthesia oral

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 of short-term and long-term treatment with pregabalin withdrawal symptoms have

been observed in some patients. The following reactions have been mentioned: insomnia, headache,

nausea, anxiety, diarrhoea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and

dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the

treatment.

Concerning discontinuation of long-term treatment of pregabalin, data suggest that the incidence and

severity of withdrawal symptoms may be dose-related.

Paediatric population

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

without secondary generalization (12-week efficacy and safety study in patients with partial onset

seizures, n=295; (pharmacokinetic and tolerability study, n=65; and 1 year open label follow on safety

study, n=54) 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 (see sections 4.2, 5.1

and 5.2).

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

Symptoms

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.

Management

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: Anti-epileptics, other anti-epileptics, ATC code: N03AX16.

The active substance, pregabalin, is a gamma-aminobutyric acid analogue [(S)-3-(aminomethyl)-5-

methylhexanoic acid].

Mechanism of action

Pregabalin binds to an auxiliary subunit (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 twice a day

dosing (BID) or three times a day (TID) dosing. Overall, the safety and efficacy profiles for BID and TID

dosing regimens were similar.

A reduction in seizure frequency was observed by Week 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 performed to evaluate the efficacy and safety of pregabalin as

adjunctive therapy for the treatment of partial onset seizures and a 1 year open label safety study in 54

paediatric patients 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 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% of subjects treated with

pregabalin 2.5 mg/kg/day (p=0.2600 versus placebo) and 22.6% of those receiving 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 3600 patients within controlled clinical trials. In these

patients, visual acuity was reduced in 6.5% of patients treated with pregabalin, and 4.8% of placebo-

treated patients. Visual field changes were detected in 12.4% of 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 anti-epileptic drugs and patients with chronic pain.

Absorption

Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations

occurring within 1 hour following both single and multiple dose administration. Pregabalin oral

bioavailability is estimated to be ≥ 90% and is independent 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 is eliminated from the systemic circulation primarily by renal excretion as 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

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 and occurred only at exposures sufficiently in excess of therapeutic exposure or were

associated with spontaneous degenerative processes in male reproductive organs in the rat. Therefore the

effects were considered of little or no clinical relevance.

Pregabalin is not genotoxic based on results of a battery of in vitro and in vivo tests.

Two-year carcinogenicity studies with pregabalin were conducted in rats and mice. No 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

Hydroxylpropylcellulose

Maize starch

Talc

Capsules shell

Iron oxide yellow (E172)

Titanium dioxide (E171)

Erythrosine (E127)

Gelatin

Sodium laurilsulfate

Printing ink

Shellac

Iron oxide black (E172)

Macrogol

Ammonia solution, concentrated

Potassium hydroxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Blister: Store in the original package in order to protect from moisture.

Bottle: Keep the bottle tightly closed in order to protect from moisture.

6.5 Nature and contents of container

Pregabalin Mylan 25 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 21, 56, 84 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 56 x 1, 84 x 1 and 100 x 1 hard capsules.

Pregabalin Mylan 50 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 21, 56, 84 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 84 x 1 and 100 x 1 hard capsules.

Pregabalin Mylan 75 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 56 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 14 x 1, 56 x 1 and 100 x 1 hard capsules.

HDPE bottle pack containing 200 hard capsules.

Pregabalin Mylan 100 mg hard capsules

PVC/PVDC-Al blister pack containing 21, 84 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 84 x 1 and 100 x 1 hard capsules

Pregabalin Mylan 150 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 56 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 14 x 1, 56 x 1 and 100 x 1 hard capsules.

HDPE bottle pack containing 200 hard capsules

Pregabalin Mylan 200 mg hard capsules

PVC/PVDC-Al blister pack containing 21, 84 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 84 x 1 and 100 x 1 hard capsules.

Pregabalin Mylan 225 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 56 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 56 x 1 and 100 x 1 hard capsules.

Pregabalin Mylan 300 mg hard capsules

PVC/PVDC-Al blister pack containing 14, 56 and 100 hard capsules.

PVC/PVDC-Al perforated unit dose blister pack containing 56 x 1 and 100 x 1 hard capsules.

HDPE bottle pack containing 200 hard capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Generics [UK] Limited

Station Close

Potters Bar

Hertfordshire

EN6 1TL

United Kingdom

8. Marketing authorisation number(s)

Pregabalin Mylan 25 mg hard capsules

EU/1/15/997/001

EU/1/15/997/002

EU/1/15/997/003

EU/1/15/997/004

EU/1/15/997/005

EU/1/15/997/006

EU/1/15/997/007

EU/1/15/997/008

Pregabalin Mylan 50 mg hard capsules

EU/1/15/997/009

EU/1/15/997/010

EU/1/15/997/011

EU/1/15/997/012

EU/1/15/997/013

EU/1/15/997/014

EU/1/15/997/015

Pregabalin Mylan 75 mg hard capsules

EU/1/15/997/016

EU/1/15/997/017

EU/1/15/997/018

EU/1/15/997/019

EU/1/15/997/020

EU/1/15/997/021

EU/1/15/997/022

Pregabalin Mylan 100 mg hard capsules

EU/1/15/997/023

EU/1/15/997/024

EU/1/15/997/025

EU/1/15/997/026

EU/1/15/997/027

Pregabalin Mylan 150 mg hard capsules

EU/1/15/997/028

EU/1/15/997/029

EU/1/15/997/030

EU/1/15/997/031

EU/1/15/997/032

EU/1/15/997/033

EU/1/15/997/034

Pregabalin Mylan 200 mg hard capsules

EU/1/15/997/035

EU/1/15/997/036

EU/1/15/997/037

EU/1/15/997/038

EU/1/15/997/039

Pregabalin Mylan 225 mg hard capsules

EU/1/15/997/040

EU/1/15/997/041

EU/1/15/997/042

EU/1/15/997/043

EU/1/15/997/044

Pregabalin Mylan 300 mg hard capsules

EU/1/15/997/045

EU/1/15/997/046

EU/1/15/997/047

EU/1/15/997/048

EU/1/15/997/049

EU/1/15/997/050

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 25 June 2015

Date of last renewal:

10. Date of revision of the text

May 2018

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.

Company Contact Details

Generics UK T/A Mylan

Address

Building 4, Trident Place, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL

Telephone

+44 (0)1707 853 000

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