Prednisolone 30mg tablets

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

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Active ingredient:
Prednisolone
Available from:
Accord Healthcare Ltd
ATC code:
H02AB06
INN (International Name):
Prednisolone
Dosage:
30mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: ; GTIN: 5012617026309
Authorization number:
PL 00142/0846

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Prednisolone, Tablets, 2.5, 5, 10,

20, 25 & 30mg, 28s, 56s - UK

296x210 (Reel Fed)

50999609

Leaflet for Blisters

3695

24-03-21

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Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg, 30mg Tablets PIL - UK

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Profile

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02

Version 2

01.11.2017

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BBBB1052 50999609

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

Depression

Mania in patients without a history of psychiatric

illness

Benign pressure increase in the skull

Breakdown of bone tissue, tendon rupture.

Not known (frequency cannot be estimated from the

available data):

Increased number of white blood cells

(leukocytosis)

Withdrawal syndrome when reducing the dose

(see section 3)

Lowered blood pH, decreased blood potassium,

elevated blood fats, impaired sugar tolerance,

accumulation of fatty tissue at secluded places in

the body, increased appetite (which can lead to

weight gain)

Emotional symptoms (such as elation,

emotional instability, drug dependence), mental

disorder (such as delusions, hallucinations and

schizophrenia), personality change, confusion,

anxiety, mood swings, abnormal behaviour, sleep

problems, irritability

Seizures, problems with memory, intellectual

disturbance, dizziness, headache, increased

amount of fat around the spinal cord

Acid reduction (central serous chorioretinopathy),

protruding eyes, blurred vision

Heart failure (in susceptible patients)

Slow heart rate

Blood clots

Hiccups

Gastric ulcer, hole (perforation) in the gut,

inflammation of the pancreas, inflammation and

ulcers of the oesophagus, swollen abdomen,

abdominal pain, diarrhoea, digestive problems,

nausea

Increased hairiness in women, bleeding of the

skin, bruising, redness of the skin, sweating,

stretch marks (blue-red patches on the chest and

abdomen), itching, hives, acne

Muscle weakness, muscle aches, bone fractures

without prior trauma, joint breakdown, joint pain

Irregular menstrual periods

Tiredness, feeling ill

Increased amount of calcium in the urine, elevated

liver enzymes (alanine aminotransferase, aspartate

aminotransferase), elevated alkaline phosphatase

in the blood, elevated levels of blood urea (seen in

blood tests), weaker reaction to skin tests.

Reporting of side effects

If you get any side effects, talk to your doctor,

pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report side

effects directly via the Yellow Card Scheme Website:

www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store Prednisolone Tablets

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 or the foil blister strip. The

expiry date refers to the last day of that month.

2.5mg; 5 mg tablets

Do not store above 25°C.

Keep the blister packs in the outer carton in order to

protect from light.

10 mg; 20 mg; 25 mg; 30 mg tablets

Keep the blister packs in the outer carton in order to

protect from light.

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 Prednisolone Tablets contain

The active substance is prednisolone. Each tablet

contains either 2.5mg, 5mg, 10mg, 20mg, 25mg or

30mg of the active ingredient.

The tablet also contains lactose monohydrate,

pregelatinised starch, sodium starch glycolate (type

A), iron oxide yellow (E172), iron oxide red (E172),

glycerol dibehenate, magnesium stearate.

What Prednisolone Tablets look like and

contents of the pack

2.5mg tablet

Yellow, 7mm, round, flat, tablet, with a score line on

one side, imprinted with “A610” on one side and “2.5”

on the other.

5mg tablet

White, 7mm, round, flat, tablet, with a score line on

one side, imprinted with “A620” on one side and “5”

on the other.

10mg tablet

Red, 7mm, round, flat, tablet, with a score line on one

side, imprinted with “A630” on one side and “10” on

the other.

20mg tablet

Red, 9mm, round, flat, tablet, with a score line on one

side, imprinted with “A640” on one side and “20” on

the other.

25mg tablet

White, 9mm, round, flat, tablet, with a score line on

one side, imprinted with “A650” on one side and

“25” on the other.

30mg tablet

Yellow, 9mm, round, flat, tablet, with a score line on

one side, imprinted with “A670” on one side and

“30” on the other.

They are available in packs of 28 tablets. The 25mg

tablet is also available in packs of 56 tablets.

Marketing Authorisation Holder and

Manufacturer

Accord, Barnstaple, EX32 8NS, UK

This leaflet was last revised in March 2021

Prednisolone is a steroid medicine, prescribed

for many different conditions, including serious

illnesses.

You need to take it regularly to get the maximum

benefit.

Don’t stop taking this medicine without talking

to your doctor – you may need to reduce the dose

gradually.

Prednisolone can cause side effects in some

people (read section 4 below). Some problems

such as mood changes (feeling depressed, or

‘high’), or stomach problems can happen straight

away. If you feel unwell in any way, keep taking

your tablets, but see your doctor straight away.

Some side effects only happen after weeks or

months. These include weakness of arms and legs,

or developing a rounder face (read section 4 for

more information).

If you take it for more than 3 weeks, you will get

a blue ‘steroid card’: always keep it with you and

show it to any doctor or nurse treating you.

Keep away from people who have chickenpox

or shingles, if you have never had them. They

could affect you severely. If you do come into

contact with chickenpox or shingles, see your

doctor straight away.

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 Prednisolone Tablets are and what

they are used for

What you need to know before you take

Prednisolone Tablets

How to take Prednisolone Tablets

Possible side effects

How to store Prednisolone Tablets

Contents of the pack and other information

1.

What Prednisolone Tablets are and what

they are used for

Prednisolone Tablets belong to a group of medicines

called steroids. Their full name is corticosteroids. These

corticosteroids occur naturally in the body, and help

to maintain health and well-being. Boosting your

body with extra corticosteroids (such as Prednisolone

Tablets) is an effective way to treat various illnesses

involving inflammation in the body. Prednisolone

Tablets reduce this inflammation, which could

otherwise go on making your condition worse. You

must take this medicine regularly to get maximum

benefit from it.

Prednisolone Tablets are used in a wide range

of inflammatory and auto-immune conditions

including:

allergies, including severe allergic reactions

inflammation affecting the:

lungs, including asthma

blood vessels and heart

bowel or kidneys

muscles and joints, including rheumatoid arthritis

eye or nervous system

skin conditions

some infections

some cancers, including leukaemia, lymphoma and

myeloma

to prevent organ rejection after a transplant.

Also:

to boost steroid levels when the body is not making

enough natural steroid on its own

to treat high calcium levels.

2.

What you need to know before you take

Prednisolone Tablets

Do not take Prednisolone Tablets if you:

are allergic to prednisolone or any of the other

ingredients of this medicine (listed in section 6).

have a fungal infection

have recently had any ‘live’ vaccinations.

Warnings and precautions

Talk to your doctor or pharmacist before taking

Prednisolone Tablets if you have:

an infection or get an infection while being treated

with prednisolone

underactive thyroid gland (hypothyroidism)

liver disease or kidney failure

or have had seizures

myasthenia gravis (a disease that causes muscle

weakness)

tuberculosis or have ever been treated for

tuberculosis

Prednisolone 2.5mg, 5mg, 10mg,

20mg, 25mg and 30mg Tablets

Package leaflet: Information for the patient

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296x210 Leaflet Reel Fed Bi Fold Profile (BST)

Dimensions:

Component:

Date Sent:

Technologist:

Technically Approved

Pharmacode:

JDE No.:

Prednisolone, Tablets, 2.5, 5, 10,

20, 25 & 30mg, 28s, 56s - UK

296x210 (Reel Fed)

50999609

Leaflet for Blisters

3695

24-03-21

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

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Non Printing Colours

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Originator:

Origination Date:

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Dimensions:

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Supplier:

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Details

Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg, 30mg Tablets PIL - UK

Black

Profile

BBBB1052

C.Grant

29/03/2021

30/03/2021

C.Grant

296x210

8.5pt

Accord Barnstaple

02

Version 2

01.11.2017

page 2

page 3

gastric ulcer, duodenal ulcer or inflammatory bowel

disease (e.g. ulcerative colitis or diverticulitis)

diabetes

heart disease, e.g. heart failure or high blood

pressure

had blood clots in the past (e.g. vein thrombosis) or

have blood clots

mood swings or psychotic tendencies

any drug allergy

osteoporosis

adrenal tumour (phaeochromocytoma)

new surgically created blood vessels or intestinal

connections

scleroderma (also called systemic sclerosis, an

autoimmune disease) as daily doses of 15mg or

more can increase the risk of a serious complication

called acute kidney crisis. Signs of acute kidney

crisis include high blood pressure and decreased

urine output. Your doctor may advise you to check

your blood pressure and urine levels regularly.

Contact your doctor if during treatment you:

get serious psychological side effects, e.g.

depression and suicidal thoughts. These can also

occur when you stop taking prednisolone.

experience blurred vision or other visual

disturbances.

are subjected to unusually severe physical or

mental strain of any kind (e.g. infection, surgery,

trauma) while you are being treated with

prednisolone. The dose may need to be increased.

Increased susceptibility to infections

Prednisolone treatment can reduce your resistance

to infections, making it easier for you to contract

infections during treatment. Chickenpox and measles

can become more serious when taking cortisone

preparations. Therefore, if you have not previously

had these diseases, you should avoid exposing

yourself to chickenpox or measles during treatment

and talk to a doctor straight away if this should still

happen.

You are more likely to develop infections whilst

taking Prednisolone Tablets, and existing infections

may become worse, especially during periods

of stress. Certain infections can be serious if not

controlled.

You may become very ill if you get chickenpox

whilst taking Prednisolone Tablets. You should

avoid contact with people who have chickenpox

or shingles whilst taking, and for up to 3 months

after you have stopped taking, Prednisolone

Tablets. Do not stop taking Prednisolone Tablets.

You should avoid contact with people who have

measles.

If you need to be vaccinated during prednisolone

treatment, tell your doctor about your treatment

before you receive the vaccination.

Corticosteroids can cause growth retardation in

infants, children and diseases and therefore long-term

use should be avoided. If long-term use is necessary,

the growth of infants and children will be closely

monitored by the physician.

Other medicines and Prednisolone Tablets

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines

including medicines obtained without a prescription.

It is especially important that your doctor know if you

are taking any of the following medicines:

rifampicin, isoniazid (to treat tuberculosis)

blood thinners

carbamazepine, phenobarbital, phenytoin (anti-

epilepsy drug)

anticholinergics (e.g. medicines for Parkinson’s

disease or asthma)

cholinesterase inhibitors (for myasthenia gravis or

Alzheimer’s disease)

insulin or diabetes drugs in the form of tablets.

Cortisone preparations can impair the blood sugar

lowering effect of diabetes drugs

cobicistat (for HIV infection)

oestrogens (e.g. birth control pills)

acetylsalicylic acid or other non-steroidal anti-

inflammatory agents (NSAIDs) (used to treat

pain and inflammation). The risk of peptic ulcer

may increase when combined with cortisone

preparations

thiazides, furosemide, ethacrylic acid (potassium-

lowering diuretics)

xanthines (e.g. theophylline, for treating asthma)

beta-2 stimulants (e.g. salbutamol, terbutaline,

salmeterol, formoterol, for treating asthma)

amphotericin B (antibiotic for fungal infection).

If you need to be vaccinated, tell your doctor that you

are taking Prednisolone Tablets.

Pregnancy and breast-feeding

Pregnancy

If you are pregnant, think you may be pregnant

or are planning to have a baby, ask your doctor or

pharmacist for advice before taking this medicine.

Breast-feeding

If you are breast-feeding you must tell your doctor

before you start the treatment. Your doctor will want

to examine your baby during your time of treatment.

Small amounts of steroids are present in breast milk.

Driving and using machines

Dizziness, visual disturbances and fatigue can occur

when using prednisolone. If you experience such

symptoms, do not drive or use machines. You are

responsible for assessing whether you are in a

position to drive a motor vehicle or perform work that

requires increased attention. One of the factors that

may affect your ability in these respects is the use of

drugs because of their effects and / or side effects. A

description of these effects and side effects can be

found in other sections. Read all the information in

this leaflet for guidance. Discuss with your doctor or

pharmacist if you are unsure.

Prednisolone Tablets contain lactose

If you have been told by your doctor that you have

an intolerance to some sugars, contact them before

taking this medicine.

Information on sodium content

This medicine contains less than 1 mmol sodium (23

mg) per tablet, that is to say essentially ‘sodium-free’.

3. How to take Prednisolone Tablets

You will be supplied with a ‘Steroid Treatment

Card’ which includes important details of your

treatment. This card should be carried at all times.

Always take this medicine exactly as your doctor or

pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Different illnesses require different doses of

Prednisolone Tablets. Depending on your illness your

daily dose may be between 5 and 60mg. In some

cases you may be instructed to take it every other day.

Your doctor will decide when and how to treat you

with Prednisolone Tablets.

Once your condition starts to get better, your doctor

may change your dosage to a lower one. Your doctor

may also reduce your dosage before stopping

treatment completely. This may depend on your

illness, your dosage and how long you have been

taking this medicine. In all cases you should be careful

to follow any changes.

Treatment of the elderly

When steroids are taken by elderly patients some

of the unwanted side effects can be more serious

especially brittle bone disease, diabetes, high blood

pressure, infections and thinning of the skin.

Whilst you are taking Prednisolone Tablets, if you

develop a chickenpox, shingles, measles or any

infection tell your doctor straight away (refer to

section 2 ‘Increased susceptibility to infections’).

Your doctor will give you a steroid treatment card. You

must carry it with you at all times. You should show

your steroid treatment card to anyone who is giving

you treatment such as a doctor, nurse or dentist.

Mental problems while taking Prednisolone

Tablets

Mental health problems can happen while taking

steroids like Prednisolone Tablets (see also Section 4

Possible side effects).

These illnesses can be serious.

Usually they start within a few days or weeks of

starting the medicine.

They are more likely to happen at high doses.

Most of these problems go away if the dose is

lowered or the medicine is stopped. However, if

problems do happen they might need treatment.

Talk to a doctor if you (or someone taking this

medicine), show any signs of mental problems. This is

particularly important if you are depressed, or might

be thinking about suicide. In a few cases, mental

problems have happened when doses are being

lowered or stopped.

Use in children and adolescents

The use of steroids can slow down normal growth of

children and adolescents. In order to lessen this effect

the tablets are often taken in a single dose every

other day.

If you take more Prednisolone Tablets than you

should

If you (or someone else) swallow a lot of tablets

at the same time, or you think a child may have

swallowed any, contact your nearest hospital casualty

department or tell your doctor immediately.

Show any leftover medicines or the empty packet to

the doctor.

If you forget to take Prednisolone Tablets

If you forget to take a dose, take one as soon as you

remember and then your next dose at the usual time.

Never take a double dose to make up for a forgotten

dose.

If you stop taking Prednisolone Tablets

If you stop taking the tablets suddenly you may

develop muscle or joint pain, conjunctivitis, fever,

weight loss, painful itchy skin lumps or runny nose.

In some severe cases a drop in blood pressure and

death may occur. If you have been given Prednisolone

Tablets for more than 3 weeks your doctor will ensure

that your dose is gradually reduced so as to avoid any

withdrawal symptoms.

It is important that you complete the course of

treatment as per your doctor’s instructions.

Talk to your doctor before you stop taking the

tablets and follow their advice.

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.

Contact your doctor immediately if the following

serious side effects occur:

Not known (frequency cannot be estimated from the

available data):

Severe allergic reaction including angioedema.

Symptoms may include: swelling of the face,

tongue or throat, difficulty swallowing, hives and

difficulty breathing, fever, drop in blood pressure.

Pheochromocytoma crisis, symptoms may include:

anxiety, headache, palpitations, sweating, pale skin.

Acute renal crisis (in patients already suffering from

scleroderma, an autoimmune disease, see section

2, Warnings and precautions). Symptoms may

include: high blood pressure and decreased urine

output.

Suicidal ideation (see section 2, Warnings and

precautions).

Other Side effects:

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

Infections, the immunosuppressive effect of

prednisolone may also cause infections to flare up

again (e.g. tuberculosis)

Lower concentration of certain hormones,

cushings-like appearance, growth retardation in

children

Low levels of potassium, build-up of sodium in

the body, increased sugar in the blood and urine,

osteoporosis

Swelling due to fluid accumulation, high blood

pressure

Thinner skin, impaired wound healing

Muscle wasting.

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

Mental disorders (at high doses)

Cataracts, glaucoma.

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Read the complete document

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Prednisolone 30mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 30 mg prednisolone.

Excipient with known affect

Each 30mg tablet contains 153.4mg of Lactose monohydrate

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablets

30mg tablet

Yellow, 9mm, round, flat, tablet, with a score line on one side, imprinted with

“A670” on one side and “30” on the other.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Allergy and anaphylaxis: bronchial asthma, drug hypersensitivity reactions, serum

sickness, angioneurotic oedema, anaphylaxis, incapacitating allergies unresponsive to

conventional treatment.

Arteritis/collagenosis: giant cell arteritis/polymyalgia rheumatica, mixed connective

tissue disease, polyarteritis nodosa, polymyositis.

Blood disorders: haemolytic anaemia (auto-immune), leukaemia (acute and chronic

lymphocytic), lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura.

Cardiovascular disorders: post-myocardial infarction syndrome, rheumatic fever

with severe carditis.

Endocrine disorders: primary and secondary adrenal insufficiency, congenital

adrenal hyperplasia.

Gastro-intestinal disorders: regional ileitis (Crohn's disease), ulcerative colitis,

persistent coeliac syndrome (coeliac disease unresponsive to gluten withdrawal),

auto-immune chronic active hepatitis, multisystem disease affecting liver, biliary

peritonitis.

Hypercalcaemia: sarcoidosis, vitamin D excess.

Infections (with appropriate chemotherapy): helminthic infestations, Herxheimer

reaction, infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult),

tuberculous meningitis, rickettsial disease.

Muscular disorders: polymyositis, dermatomyositis.

Neurological disorders: infantile spasms, Shy-Drager syndrome, sub-acute

demyelinating polyneuropathy.

Ocular disease: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the

orbit, giant cell arteritis, malignant ophthalmic Graves disease.

Renal disorders: lupus nephritis, acute interstitial nephritis, minimal change

glomerulonephritis, nephrotic syndrome.

Respiratory disease: allergic pneumonitis, asthma, occupational asthma, pulmonary

aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body,

aspiration of stomach contents, pulmonary sarcoid, drug induced lung disease, adult

respiratory distress syndrome, spasmodic croup, fulminating or disseminated

pulmonary tuberculosis when used concurrently with appropriate antituberculosis

chemotherapy.

Rheumatic disorders: rheumatoid arthritis, polymyalgia rheumatica, juvenile

chronic arthritis, psoriatic arthritis, systemic lupus erythematosus, dermatomyositis,

mixed connective tissue disease.

Skin disorders: pemphigus vulgaris, exfoliative dermatitis, bullous pemphigoid,

systemic lupus erythematosus, pyoderma gangrenosum.

Miscellaneous: sarcoidosis, hyperpyrexia, Behçets disease, immunosuppression in

organ transplantation.

4.2

Posology and method of administration

Posology

Adults and the elderly

The lowest effective dose should be used for the minimum period.

Children

Prednisolone should only be used when specifically indicated, at the lowest dose

possible and for the shortest possible time.

The initial dosage of Prednisolone may vary from 5mg to 60mg daily depending on

the disorder being treated. Divided daily dosage may be used. Administration as a

once daily dose in the morning or on alternate days can reduce the risk of

adrenocortical suppression (see Section 4.4 Special warnings and precautions for

use). In some patients this may not be possible e.g. patients with rheumatoid arthritis

with pronounced morning stiffness where an evening dose may need to be given.

The following therapeutic guidelines should be kept in mind for all therapy with

corticosteroids:

The lowest dose to produce an acceptable result should be given. Initial dosage

should be adjusted until the desired clinical response has been achieved. The dose

should be gradually reduced until the lowest dose which will maintain an adequate

clinical response is reached. As a guide, the daily dose should be reduced by 2.5 – 5

mg every second to fifth day (more rapidly at the higher initial dose levels) until the

lowest possible maintenance dose is reached. Preferably this should not exceed 10 mg

per day. Use of the lowest effective dose will tend to minimise side-effects. The

incidence of side-effects increases with dose and duration of treatment (see Section

4.4 'Special warnings and special precautions for use').

Particular care should be exercised in patients who have received higher than 7.5mg

prednisolone daily or equivalent for more than 3 weeks, owing to a greater risk of

suppression of the hypothalamic-pituitary-adrenal (HPA) axis in these patients. The

speed with which dose can be reduced is also dependent on risk of relapse of the

disease being treated. After prolonged treatment, tapering of dose below 7.5 mg

(regarded as “equivalent” to physiological levels of glucocorticoids) should be

conducted particularly cautiously.

More rapid withdrawal of systemic corticosteroid treatment that has been given for

less than 3 weeks is appropriate if it is considered that the disease is unlikely to

relapse. Withdrawal of doses of up to 40mg daily of prednisolone, or equivalent that

have been administered for less than 3 weeks is unlikely to lead to clinically relevant

HPA-axis suppression, in the majority of patients. In the following patient groups,

gradual withdrawal of systemic corticosteroid therapy should be considered even after

courses lasting 3 weeks or less:

patients who have had repeated courses of systemic corticosteroids, particularly if

taken for greater than 3 weeks.

when a short course has been prescribed within one year of cessation of long-term

therapy (months or years).

patients who may have reasons for adrenocortical insufficiency other than

exogenous corticosteroid therapy.

patients receiving doses of systemic corticosteroid greater than 40mg daily of

prednisolone (or equivalent).

patients repeatedly taking doses in the evening.

(See Section 4.4 'Special warnings and special precautions for use' and Section 4.8

'Undesirable effects')

During prolonged therapy, dosage may need to be temporarily increased during

periods of stress or during exacerbations of the disease (see Section 4.4 'Special

warnings and special precautions for use')

If there is lack of a satisfactory clinical response to Prednisolone Tablets, the drug

should be gradually discontinued and the patient transferred to alternative therapy.

Intermittent dosage regimen A single dose of PrednisoloneTablets in the morning on

alternate days or at longer intervals is acceptable therapy for some patients. When this

regimen is practical, the degree of pituitary-adrenal suppression can be minimised.

Specific dosage guidelines The following recommendations for some corticosteroid-

responsive disorders are for guidance only. Acute or severe disease may require

initial high dose therapy with reduction to the lowest effective maintenance dose as

soon as possible. Dosage reductions should not exceed 5-7.5mg daily during chronic

treatment.

Allergic and skin disorders Initial doses of 5-15mg daily are commonly adequate.

Collagenosis Initial doses of 20-30mg daily are frequently effective. Those with more

severe symptoms may require higher doses.

Rheumatoid arthritis The usual initial dose is 10-15mg daily. The lowest daily

maintenance dose compatible with tolerable symptomatic relief is recommended.

Blood disorders and lymphoma An initial daily dose of 15-60mg is often necessary

with reduction after an adequate clinical or haematological response. Higher doses

may be necessary to induce remission in acute leukaemia.

Special populations

Use in elderly Treatment of elderly patients, particularly if long-term, should be

undertaken with caution bearing in mind the more serious consequences of the

common side-effects of corticosteroids in old age (see also 'Special warnings and

special precautions for use').

Use in children: Although appropriate fractions of the adult dose may be used,

dosage will usually be determined by clinical response as in adults (see also Section

4.4 'Special warnings and special precautions for use' and Section 4.8 'Undesirable

effects'). Alternate day dosage is preferable where possible.

Method of administration

Prednisolone tablets should be taken following a meal to reduce the risk of gastric

irritation.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in

section 6.1.

Systemic fungal infection.

Administration of live vaccines is contraindicated in patients receiving

corticosteroids in immunosuppressive doses.

In those conditions when treatment with prednisolone can save lives, none of

the contraindications generally applies.

4.4

Special warnings and precautions for use

Since the complications of glucocorticoid therapy are dependent on the dose

and duration of treatment, a risk / benefit assessment must be made in each

case regarding dose and duration of treatment, as well as whether daily or

intermittent treatment should be used.

The lowest possible corticosteroid dose needed to control the disease being

treated should be used. When dose reduction is possible, it should be gradual.

Immunosuppressive effects / increased infection sensitivity

Glucocorticoids, including prednisolone, may cause increased susceptibility to

infection, masking symptoms of infection, and new infections may occur

during treatment.

Infections caused by viruses, bacteria, fungi, protozoa or helminths may be

associated with the use of corticosteroids alone or corticosteroids in

combination with other immunosuppressive agents that affect cellular

immunity, humoral immunity or the function of neutrophils. The infections

can be mild, but also difficult and in some cases fatal. The risk of infectious

complications increases with increasing dose.

Glucocorticoids should not be given during infections without concomitant

causal treatment.

Chickenpox and measles can be more serious or even fatal in non-immunized

children and adults treated with corticosteroids. Children, or adults who have

not had these diseases, and who take immunosuppressive doses of

corticosteroids, should be advised to avoid exposure to chickenpox and

measles, and to seek care when exposed.

The use of prednisolone in active tuberculosis should be limited to those cases

of fulminant or disseminated tuberculosis where the corticosteroid is used to

treat the disease in combination with appropriate tuberculosis therapy. If

corticosteroids are indicated in patients with latent tuberculosis or tuberculin

reactivity, careful monitoring is necessary as the disease can be reactivated. In

long-term corticosteroid therapy, these patients should receive tuberculosis

prophylaxis.

High dose corticosteroids may interfere with active immunization.

Vaccination with live vaccine should be done under close supervision and not

in patients on long-term treatment with corticosteroids in immunosuppressive

doses.

Immune system

Since rare cases of skin reactions and anaphylactic / anaphylactoid reactions

have occurred in patients treated with corticosteroids, appropriate precautions

should be taken prior to administration, especially if the patient has previously

had an allergic reaction to any drug.

Endocrine system

Long-term treatment with pharmacological doses of corticosteroid may lead to

secondary adrenal insufficiency. The risk can be reduced by giving the

treatment every other day (see section 4.2).

Patients who receive corticosteroid maintenance therapy and are exposed to

unusual stresses (e.g. infection, surgery or trauma) need higher corticosteroid

doses before, during and after the stressful situation.

Abrupt termination of treatment may lead to acute adrenal insufficiency which

may be fatal. The risk of secondary adrenal insufficiency can be reduced by

gradually decreasing the dose. This type of relative insufficiency may persist

for months after the end of treatment, so hormone replacement therapy should

be reintroduced in stressful situations occurring during this time period. Since

the secretion of mineral corticoids may be impaired, salts and / or mineral

corticoids should be administered simultaneously.

A "steroid withdrawal syndrome", apparently without associated with adrenal

insufficiency, may also occur following abrupt withdrawal of glucocorticoids.

This syndrome causes symptoms such as anorexia, nausea, vomiting, lethargy,

headache, fever, joint pain, desquamation, myalgia, weight loss and / or

hypotension. These effects are believed to be due to the sudden change in

glucocorticosteroid concentration rather than to low corticosteroid levels.

Patients with hypothyroidism or liver cirrhosis will have an enhanced effect of

corticosteroids.

Pheochromocytoma-related crisis, which may be fatal, has been reported

following systemic corticosteroid administration. Corticosteroids should only

be administered to patients with suspected or identified pheochromocytoma

following consideration of individual risk / benefit.

Metabolism and nutrition

Corticosteroids, including prednisolone, can raise blood sugar levels,

exacerbate existing diabetes and increase the risk of developing diabetes in

patients on long-term corticosteroid therapy.

Mental disorders

Potentially serious mental disorders may occur during treatment with

corticosteroids including prednisolone. It can be anything from euphoria, sleep

disorders, mood swings, personality changes and severe depression to

psychotic manifestations. Existing emotional instability and psychotic

tendencies can also be exacerbated by corticosteroids (see section 4.8). The

symptoms typically begin within a few days or weeks after the start of

treatment. Most reactions return after dose reduction or withdrawal, but

specific treatment may be necessary.

Psychiatric effects have been reported with the withdrawal of corticosteroids,

the frequency is unknown. Patients / caregivers should be encouraged to seek

medical care if the patient shows mental symptoms, especially if depression or

suicidal thoughts are suspected. Patients / caregivers should be aware that

mental disorders may occur either during or immediately after dose reduction /

discontinuation of systemic steroids.

Central and peripheral nervous system

Corticosteroids should be used with caution in patients with seizures.

Heart

Side effects of glucocorticoids on the cardiovascular system, for example

dyslipidemia and hypertension, can predispose in treated patients with existing

cardiovascular risk factors for additional cardiovascular events at high doses

and prolonged treatment times. Corticosteroids should therefore be introduced

to these patients only after careful consideration, and risk-modifying measures

as well as extra cardiac monitoring should be considered as needed. Low dose

and treatment every other day can reduce the complications of corticosteroid

treatment.

Blood vessels

Since cortisone has been reported to increase the blood clotting tendency in

rare cases, thereby accelerating the development of intravascular thrombosis,

thromboembolism and thrombophlebitis, corticosteroids should be used with

caution in patients with thromboembolic disorders.

Gastrointestinal tract

High doses of corticosteroids can cause acute pancreatitis.

There are no conclusive data that states that corticosteroids cause ulcers.

Glucocorticoid therapy can mask peritonitis and other signs and symptoms

associated with gastrointestinal conditions such as perforation, obstruction or

pancreatitis. In combination with NSAIDs, the risk of gastrointestinal ulcers is

increased.

Corticosteroids should therefore be used with caution in non-specific

ulcerative colitis if there is a likelihood of imminent perforation, abscess or

other pyogenic infection, diverticulitis, newly created anastomoses, or active

or latent peptic ulcer.

Liver and biliary tract

Diseases of the liver and bile ducts have been reported rarely and in the

majority of these cases the condition was reversible after discontinuation of

treatment. Appropriate monitoring measures are required.

Musculoskeletal system

Acute myopathy has been reported with high corticosteroid doses, most often

in patients with neuromuscular transmission disorders (e.g., myasthenia

gravis), or in patients concomitantly treated with anticholinergics, e.g.

neuromuscular blocking drugs (such as pancuronium) (see section 4.5). This

acute myopathy is generalized, may involve eye and respiratory muscles, and

may lead to tetraparesis. Elevated creatine kinase may occur. Clinical

improvement or recovery after discontinuation of corticosteroid therapy may

take weeks or years.

Corticosteroids should be used with caution in patients with osteoporosis.

Kidneys and urinary tract

Corticosteroids should be used with caution in patients with renal

insufficiency.

Acute renal crisis (renal crisis in scleroderma)

Caution is required in patients with systemic sclerosis as an increased

incidence of (possibly fatal) renal crisis in scleroderma, with hypertension and

decreased urine output, has been observed with a daily prednisolone dose of

15 mg or more. Therefore, blood pressure and renal function (S-creatinine)

should be routinely monitored. In case of suspected renal crisis, blood pressure

should be kept under close control.

Effects on electrolytes and fluid balance

Systemic corticosteroids should be used with caution in patients with heart

failure or hypertension. Medium and high doses of hydrocortisone or cortisone

can lead to increased blood pressure, salt and water retention and increased

potassium secretion. These effects are less likely with synthetic derivatives,

except when used in high doses. Dietary restrictions with lower salt intake and

potassium supplementation may be necessary.

All corticosteroids increase calcium excretion.

Eyes

Syncope disorder can be reported in systemic and topical use of

corticosteroids. If a patient comes with symptoms such as blurred vision or

other visual disturbances, consideration should be given to referring the patient

to ophthalmologist for investigation of possible causes. These may include

cataracts, glaucoma or rare diseases such as central serous chorioretinopathy

(CSCR), which have been reported following the use of systemic and topical

corticosteroids.

Use in children

Corticosteroids cause growth inhibition in infants, children and adolescents,

therefore avoid long-term treatment with pharmacological doses. If long-term

treatment is required, the infant / child's growth and development should be

closely monitored (see section 4.2). Infants and children who are on long-term

corticosteroid therapy are at particular risk of developing elevated intracranial

pressure.

Excipients

Patients with rare hereditary problems of galactose intolerance, total lactase

deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to

say essentially ‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

The following combinations with Prednisolone Pfizer may require dose

adjustment.

Phenobarbital, phenytoin, carbamazepine:

Phenobarbital (which is also the metabolite of primidone), phenytoin and

carbamazepine alone and in combination, induces the metabolism of

hydrocortisone, prednisolone and methylprednisolone (shown in children with

asthma) with increased dose requirements as a result. The interaction probably

applies to the whole group of glucocorticoids.

Non-steroidal anti-inflammatory drugs:

1) The incidence of gastrointestinal bleeding and ulceration may increase if

corticosteroids are given with NSAIDs.

2) Corticosteroids may increase the clearance of high doses of acetylsalicylic

acid, which may lead to lower salicylate levels in the serum. Salicylate levels

in serum may increase upon discontinuation of corticosteroid therapy, which

could lead to an increased risk of toxic effects of salicylate.

Diabetes drugs:

Glucocorticoids increase blood sugar levels. Patients with diabetes mellitus

receiving concomitant insulin and / or oral hypoglycaemic agents may need to

adjust the dose of such treatment.

Estrogens (also oral contraceptives containing estrogens):

estrogens increase the concentration of transcortin. The effect of

glucocorticoids that bind to transcortin can be enhanced and dose adjustments

may be needed if estrogens are added or removed from a stable treatment

regimen.

Potassium Reducing Agents:

Potassium-reducing diuretics (e.g., thiazides, furosemide, ethacrynic acid) and

other drugs that reduce the amount of potassium such as amphotericin B,

xanthines and beta2-agonists, may potentiate the potassium-lowering effect of

glucocorticoids. Serum potassium should be closely monitored in patients

receiving glucocorticoids and potassium reducing agents.

Rifampicin:

Rifampicin induces the microsomal oxidation of glucocorticoids

(hydrocortisone, prednisolone, methylprednisolone). This leads to an increased

steroid need during rifampicin treatment and reduced steroid need after such

treatment.

Isoniazid:

Prednisolone also has a potential effect which results in increased acetylation

rate and clearance of isoniazid.

Oral anticoagulants:

There are reports of altered effects of anticoagulants given concurrently with

prednisolone. Prothrombin time (INR) should be monitored during treatment.

CYP3A inhibitors, including medicinal products containing cobicistat:

These are expected to increase the risk of systemic side effects. The

combination should be avoided unless the benefit outweighs the increased risk

of systemic side effects of corticosteroids, and if so, patients should be

monitored for systemic adverse events of corticosteroids.

Anticholinergic, neuromuscular blockers:

Corticosteroids may affect the effect of anticholinergics.

1) Acute myopathy has been reported with concomitant use of high doses of

corticosteroids and anticholinergics such as neuromuscular blockers (see

section 4.4).

2) Antagonism with the neuromuscular blocking effect of pancuronium and

vecuronium has been reported in patients taking glucocorticosteroids. This

interaction can be expected with all competitive neuromuscular blockers.

Anticholinesterases:

Interaction between glucocorticoids and anticholinesterases such as

ambenonium, neostigmine and pyridostigmine may lead to significant potency

in myasthenia gravis.

If possible, treatment with anticholinesterase should be discontinued at least

24 hours before administration of glucocorticoid.

4.6

Fertility, pregnancy and lactation

Fertility

Animal studies have shown that corticosteroids impair fertility (see section

5.3).

Pregnancy

In animal studies, corticosteroids have been shown to give rise to various types

of malformations (palate gap, skeletal malformations, see section 5.3).

The relevance in humans is unknown.

After long-term treatment, reduced placental and birth weight have been

observed in humans and animals.

In addition, there is a risk of adrenal insufficiency in the newborn during long-

term treatment. Therefore, during pregnancy, corticosteroids should be given

after special consideration.

Breast-feeding

Prednisolone passes into breast milk, but the risk of affecting the baby seems

unlikely with therapeutic doses.

4.7

Effects on ability to drive and use machines

Read the complete document

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

1

Public Assessment Report

Decentralised Procedure

Prednisolone 2.5mg Tablets

Prednisolone 5mg Tablets

Prednisolone 10mg Tablets

Prednisolone 20mg Tablets

Prednisolone 25mg Tablets

Prednisolone 30mg Tablets

(Prednisolone)

Procedure No: UK/H/6012/001-006/DC

UK Licence Number: PL 24668/0296-301

Caduceus Pharma Ltd.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

2

LAY SUMMARY

Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

(prednisolone, tablet, 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg).

This is a summary of the Public Assessment Report (PAR) for Prednisolone 2.5mg, 5mg, 10mg, 20mg,

25mg and 30mg Tablets (PL 24668/0296-301; UK/H/6012/001-006/DC). It explains how Prednisolone

2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets were assessed and their authorisation recommended,

as well as their conditions of use. It is not intended to provide practical advice on how to use

Prednisolone 2.5, 5mg, 10mg, 20mg, 25mg and 30mg Tablets.

The products will be collectively referred to as Prednisolone Tablets throughout the remainder of this

public assessment report (PAR).

For practical information about using Prednisolone Tablets, patients should read the package leaflet or

contact their doctor or pharmacist.

What are Prednisolone Tablets and what are they used for?

Prednisolone 2.5 mg, 5mg and 10mg Tablets are ‘generic medicines’. This means that Prednisolone 2.5

mg, 5mg and 10mg Tablets are similar to ‘reference medicines’ already authorised in the European

Union (EU) called Prednisolon Pfizer 2.5 mg, 5 mg and 10 mg (Pfizer AB, Sweden).

Prednisolone 20mg, 25mg and 30mg Tablets are ‘hybrid generic medicines’. This means that they are

similar to a reference medicine containing the same active substance, but are available at a higher

strength (20mg, 25mg and 30mg tablets instead of 2.5 mg, 5 mg and 10 mg tablets as the reference

medicine).

The reference medicine for Prednisolone 20mg Tablets is Prednisolon Pfizer 10 mg (Pfizer AB,

Sweden).

The reference medicine for Prednisolone 25mg Tablets is Prednisolon Pfizer 2.5 mg (Pfizer AB,

Sweden).

The reference medicine for Prednisolone 30mg Tablets is Prednisolon Pfizer 5 mg (Pfizer AB, Sweden).

Prednisolone Tablets belong to a group of medicines called steroids. Their full name is corticosteroids.

These corticosteroids occur naturally in the body. Boosting the body with extra corticosteroids (such as

Prednisolone Tablets) is an effective way to treat various illnesses involving inflammation in the body.

Prednisolone Tablets are used in a wide range of inflammatory and auto-immune conditions including:

allergies, including severe allergic reactions

inflammation affecting the:

- lungs, including asthma

- blood vessels and heart

- bowel or kidneys

- muscles and joints, including rheumatoid arthritis

- eye or nervous system

skin conditions

some infections

some cancers, including leukaemia, lymphoma and myeloma

to prevent organ rejection after a transplant.

Also:

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

3

to boost steroid levels when the body is not making enough natural steroid on its own

to treat high calcium levels.

How do Prednisolone Tablets work?

Prednisolone, the active ingredient, helps to maintain health and wellbeing. Prednisolone acts by

reducing the inflammation caused by these illnesses, which could otherwise go on making such

conditions worse. The patient must take this medicine regularly to get maximum benefit from it.

How are Prednisolone Tablets used?

The pharmaceutical form of this medicine is a tablet and the route of administration is oral (by mouth).

The patient will be supplied with a ‘Steroid Treatment Card’ which includes important details of their

treatment. This card should be carried at all times.

The patient must always take this medicine exactly as their doctor or pharmacist has told them. The

patient should check with their doctor or pharmacist if they are not sure.

Different illnesses require different doses of Prednisolone Tablets. Depending on the patient’s illness,

their daily dose may be between 5 and 60 mg. In some cases the patient may be instructed to take it

every other day.

The patient’s doctor will decide when and how to treat them with Prednisolone Tablets.

Once the patient’s condition starts to get better, their doctor may change their dosage to a lower one. The

patient’s doctor may also reduce their dosage before stopping treatment completely. This may depend on

the patient’s illness, the dosage and how long they have been taking this medicine. In all cases the

patient should be careful to follow any changes.

Treatment of the elderly

When steroids are taken by elderly patients some of the unwanted side effects can be more serious

especially brittle bone disease, diabetes, high blood pressure, infections and thinning of the skin.

Please read section 3 of the package leaflet for detailed dosing recommendations, the route of

administration, and the duration of treatment.

This medicine can only be obtained with a prescription.

What benefits of Prednisolone Tablets

have been shown in studies?

As Prednisolone Tablets are generic/hybrid generic medicines of Prednisolon Pfizer 2.5 mg, 5 mg and

10 mg (Pfizer AB, Sweden), studies have been limited to tests to determine that Prednisolone Tablets are

bioequivalent/therapeutically equivalent to the reference medicines Prednisolon Pfizer 2.5 mg, 5 mg and

10 mg (Pfizer AB, Sweden). Two medicines are bioequivalent when they produce the same levels of the

active substance in the body.

What are the possible side effects of Prednisolone Tablets?

Because Prednisolone Tablets are either generic or hybrid generic medicines that are considered

bioequivalent/therapeutically equivalent to the reference medicines Prednisolon Pfizer 2.5 mg, 5 mg and

10 mg (Pfizer AB, Sweden) the benefits and possible side effects are taken as being the same as the

reference medicines.

For the full list of restrictions, see the package leaflet.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

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For the full list of all side effects reported with Prednisolone Tablets, see section 4 of the package leaflet

available on the MHRA website.

Why was Prednisolone Tablets approved?

It was concluded that, in accordance with EU requirements, Prednisolone Tablets have been shown to

have comparable quality and to be bioequivalent/be comparable to Prednisolon Pfizer 2.5 mg, 5 mg and

10 mg (Pfizer AB, Sweden). Therefore, the MHRA decided that, as for Prednisolon Pfizer 2.5 mg, 5 mg

and 10 mg (Pfizer AB, Sweden); the benefits are greater than the risks and recommended that

Prednisolone Tablets can be approved for use.

What measures are being taken to ensure the safe and effective use of Prednisolone Tablets?

A risk management plan (RMP) has been developed to ensure that Prednisolone Tablets is used as safely

as possible. Based on this plan, safety information has been included in the Summaries of Product

Characteristics (SmPCs) and the package leaflet for Prednisolone Tablets including the appropriate

precautions to be followed by healthcare professionals and patients.

Known side effects are continuously monitored. Furthermore new safety signals reported by

patients/healthcare professionals will be monitored/reviewed continuously.

Other information about Prednisolone Tablets

Malta and the UK agreed to grant marketing authorisations for Prednisolone Tablets on 21 March 2016.

Marketing authorisations were granted in the UK on 01 April 2016.

The full PAR for Prednisolone Tablets follows this summary.

For more information about use of Prednisolone Tablets, read the package leaflet, or contact your doctor

or pharmacist.

This summary was last updated in May 2016.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

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TABLE OF CONTENTS

Introduction

Page 6

Quality aspects

Page 8

Non-clinical aspects

Page 10

Clinical aspects

Page 10

User consultation

Page 16

Overall conclusion, benefit/risk assessment and

recommendation

Page 16

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I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products

Regulatory Agency (MHRA) granted Caduceus Pharma Ltd, marketing authorisations for the medicinal

products Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets (PL 24668/0296-301;

UK/H/6012/001-006/DC). The products are prescription-only medicines (POM) indicated for:

Allergy and anaphylaxis

: bronchial asthma, drug hypersensitivity reactions, serum sickness,

angioneurotic oedema, anaphylaxis, incapacitating allergies unresponsive to conventional

treatment.

Arteritis/collagenosis

: giant cell arteritis/polymyalgia rheumatica, mixed connective tissue

disease, polyarteritis nodosa, polymyositis.

Blood disorders

: haemolytic anaemia (auto-immune), leukaemia (acute and chronic

lymphocytic), lymphoma, multiple myeloma, idiopathic thrombocytopenic purpura.

Cardiovascular disorders

: post-myocardial infarction syndrome, rheumatic fever with severe

carditis.

Endocrine disorders

: primary and secondary adrenal insufficiency, congenital adrenal

hyperplasia.

Gastro-intestinal disorders

: regional ileitis (Crohn's disease), ulcerative colitis, persistent

coeliac syndrome (coeliac disease unresponsive to gluten withdrawal), auto-immune chronic

active hepatitis, multisystem disease affecting liver, biliary peritonitis.

Hypercalcaemia

: sarcoidosis, vitamin D excess.

Infections (with appropriate chemotherapy)

: helminthic infestations, Herxheimer reaction,

infectious mononucleosis, miliary tuberculosis, mumps orchitis (adult), tuberculous meningitis,

rickettsial disease.

Muscular disorders

: polymyositis, dermatomyositis.

Neurological disorders

: infantile spasms, Shy-Drager syndrome, sub-acute demyelinating

polyneuropathy.

Ocular disease

: scleritis, posterior uveitis, retinal vasculitis, pseudo-tumours of the orbit, giant

cell arteritis, malignant ophthalmic Graves disease.

Renal disorders

: lupus nephritis, acute interstitial nephritis, minimal change glomerulonephritis,

nephrotic syndrome.

Respiratory disease

: allergic pneumonitis, asthma, occupational asthma, pulmonary

aspergillosis, pulmonary fibrosis, pulmonary alveolitis, aspiration of foreign body, aspiration of

stomach contents, pulmonary sarcoid, drug induced lung disease, adult respiratory distress

syndrome, spasmodic croup, fulminating or disseminated pulmonary tuberculosis when used

concurrently with appropriate antituberculosis chemotherapy.

Rheumatic disorders

: rheumatoid arthritis, polymyalgia rheumatica, juvenile chronic arthritis,

psoriatic arthritis, systemic lupus erythematosus, dermatomyositis, mixed connective tissue

disease.

Skin disorders

: pemphigus vulgaris, exfoliative dermatitis, bullous pemphigoid, systemic lupus

erythematosus, pyoderma gangrenosum.

Miscellaneous

: sarcoidosis, hyperpyrexia, Behçets disease, immunosuppression in organ

transplantation.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

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The applications were submitted using the Decentralised Procedure (DCP), with the UK as Reference

Member State (RMS), and Malta as Concerned Member State (CMS). The applications for Prednisolone

2.5 mg, 5mg and 10mg Tablets were submitted under Article 10(1) of Directive 2001/83/EC, as

amended, as generic applications. The applications for Prednisolone 20mg, 25mg and 30mg Tablets (PL

24668/0299-301; UK/H/6012/004-006/DC) were submitted under Article 10(3) of Directive

2001/83/EC, as amended, as hybrid applications.

The reference medicinal products for these applications are Prednisolon Pfizer 2.5 mg, 5 mg and 10 mg

authorised to Pfizer AB, Sweden, on 09 March 1984 (2.5 mg and 10 mg, MA numbers 10059 and 10060

respectively) and 31st August 1973 (5 mg, MA number 8822).

The Swedish reference product is available in tablet strengths of 2.5 mg, 5 mg and 10 mg whereas the

proposed Prednisolone 20 mg, 25 mg, and 30 mg tablets represent additional tablet strengths.

Prednisolone is a synthetic corticosteroid with predominantly glucocorticoid properties. Due to its potent

anti-inflammatory and immunosuppressive actions it is widely used in a broad range of indications.

Prednisolone is approximately three times more potent on a weight for weight basis than hydrocortisone

with respect to glucocorticoid activity; however, it is considerably less potent than hydrocortisone in

mineralocorticocoid activity which reduces the side-effect profile. Orally administered prednisolone is

readily absorbed by the gastrointestinal tract and is an active form. In contrast, orally ingested

prednisone requires conversion by hepatic metabolism to prednisolone.

Two bioequivalence studies (conducted under fasting conditions) were submitted to support these

applications. Comparing the applicant’s test products Prednisolone 2.5mg and 30mg Tablets (Caduceus

Pharma Ltd) with the reference products Prednisolon Pfizer 2.5 mg and 10 mg (administered at 3 x 10

mg tablets) authorised to Pfizer AB, Sweden. The applicant has stated that the bioequivalence studies

were conducted in accordance with the clinical research guidelines laid out in the Indian Council for

Medical Research (ICMR) guidelines for biomedical research on human subjects, the current Helsinki

Declaration (Brazil 2013), ICH guidelines on Good Clinical Practice (GCP) and applicable regulatory

requirements.

With the exception of the bioequivalence studies, no new non-clinical or clinical data were submitted,

which is acceptable given that these applications were based on being a generic medicinal product of an

originator product that has been in clinical use for over 10 years.

The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in

place at all sites responsible for the manufacture, assembly and batch release of this product.

For manufacturing sites within the Community, the RMS has accepted copies of current manufacturer

authorisations issued by inspection services of the competent authorities as certification that acceptable

standards of GMP are in place at those sites.

The RMS and CMS considered that the applications could be approved at the end of procedure on 21

March 2016. After a subsequent national phase, licences were granted in the UK on 01 April 2016.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

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II

QUALITY ASPECTS

II.1

Introduction

Each tablet contains 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg or 30 mg

prednisolone, as the active

ingredient. Other ingredients consist of the pharmaceutical excipients lactose monohydrate,

pregelatinised starch, sodium starch glycolate, type A, iron oxide yellow (E172), iron oxide red (E172),

glycerol dibehenate and magnesium stearate.

All strengths of the finished product are packed in to aluminium (Al)/polyvinyl chloride (PVC) blisters

and are available in pack sizes of 28 tablets. The 25 mg strength tablets are also available in packs of 56

tablets. Not all pack sizes may be marketed.

Satisfactory specifications and Certificates of Analysis

have been provided for all packaging components.

II.2

Drug Substance

INN:

Prednisolone

Chemical name:

11β,17,21-Trihydroxypregna-1,4-diene-3,20-dione.

Structure:

Molecular formula:

Molecular weight:

360.4

Description:

White or almost white, crystalline, hygroscopic powder.

Solubility;

Very slightly soluble in water, soluble in ethanol (96 per cent) and in methanol,

sparingly soluble in acetone, slightly soluble in methylene chloride.

Prednisolone is the subject of a European Pharmacopoeia monograph.

All aspects of the manufacture and control of the active substance, prednisolone, are covered by the

European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability.

II.3.

Medicinal Product

Pharmaceutical Development

The objective of the development programme was to formulate safe, efficacious tablets containing 2.5

mg, 5 mg, 10 mg, 20 mg, 25 mg or 30 mg prednisolone per tablet, that are generic/hybrid generic

versions of the reference products Prednisolon Pfizer 2.5 mg, 5 mg and 10 mg (Pfizer AB, Sweden). A

satisfactory account of the pharmaceutical development has been provided.

Comparative

in-vitro

dissolution and impurity profiles have been provided for the proposed and

originator products.

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All excipients comply with their respective European Pharmacopoeia monographs with the exception of

iron oxide yellow (E172), iron oxide red (E172) which are in compliance the United States

Pharmacopeia and National Formulary (USP-NF). Satisfactory Certificates of Analysis have been

provided for all excipients. Suitable batch analysis data have been provided for each excipient.

With the exception of lactose monohydrate, none of the excipients contain materials of animal or human

origin. The supplier of lactose monohydrate has confirmed that the milk used in the production of

lactose monohydrate is sourced from healthy animals under the same conditons as that intended for

human consumption. In addition, the supplier has confirmed that no ruminant material of any kind is

used during the production of lactose monohydrate.

No genetically modified organisms (GMO) have been used in the preparation of this product.

Manufacture of the product

Satisfactory batch formulae have been provided for the manufacture of the products, along with an

appropriate account of the manufacturing process. The manufacturing process has been validated at pilot

scale batch size and has shown satisfactory results. The marketing authorisation holder (MAH) has

committed to perform additional process validation studies on future commercial-scale batches.

Finished Product Specification

The finished product specifications proposed are acceptable. Test methods have been described that have

been adequately validated. Batch data have been provided that comply with the release specifications.

Certificates of Analysis have been provided for all working standards used.

Stability of the Product

Finished product stability studies were performed in accordance with current guidelines on batches of

the finished product in the packaging proposed for marketing. The data from these studies support a

shelf-life of 24 months with the storage conditions ‘Keep the blister packs in the outer carton in order to

protect from light.’

Suitable post approval stability commitments have been provided to continue stability testing on batches

of finished product.

II.4

Discussion on chemical, pharmaceutical and biological aspects

There are no objections to the approval of these applications from a pharmaceutical viewpoint.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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III

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of prednisolone are well-known,

no new non-clinical studies are required and none have been provided. An overview based on the

literature review is, thus, appropriate.

The applicant’s non-clinical expert report has been written by an appropriately qualified person and is

satisfactory, providing an appropriate review of the relevant non-clinical pharmacology,

pharmacokinetics and toxicology.

III.2

Pharmacology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.3

Pharmacokinetics

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.4

Toxicology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.5

Ecotoxicity/environmental risk assessment (ERA)

Since Prednisolone Tablets are intended for generic substitution, this will not lead to an increased

exposure to the environment. An environmental risk assessment is therefore not deemed necessary

.

III.6

Discussion on the non-clinical aspects

No new non-clinical studies were conducted, which is acceptable given that the applications were based

on being generic/ hybrid generic medicinal products of originator products that have been licensed for

over 10 years.

There are no objections to the approval of these applications from a non-clinical viewpoint.

IV

CLINICAL ASPECTS

IV.1

Introduction

The clinical pharmacology of prednisolone is well-known. With the exception of data from the

bioequivalence studies detailed below, no new pharmacodynamics or pharmacokinetic data are provided

or are required for these applications.

No new efficacy or safety studies have been performed and none are required for this type of

application. A comprehensive review of the published literature has been provided by the applicant,

citing the well-established clinical pharmacology, efficacy and safety of prednisolone.

Based on the data provided, Prednisolone Tablets can be considered bioequivalent/be comparable to

Prednisolon Pfizer 2.5 mg, 5 mg and 10 mg (Pfizer AB, Sweden)

IV.2

Pharmacokinetics

Two bioequivalence studies representing extremes of the proposed range of tablet strengths (2.5 mg and

30 mg) have been supplied in support of bioequivalence for all the proposed tablet strengths. A

bracketed approach has been used due to the existence of non-proportional composition (between active

substance and core excipients) across the tablet strengths. Furthermore, prednisolone is well recognised

to display non-linear pharmacokinetics thought to be due principally to non-linear plasma protein

binding, resulting in higher clearance rates with increasing dose. Prednisolone concentrations in plasma

after single oral doses of 20 mg and 40 mg are reported to be very similar. Increasing dose would

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

11

therefore be predicted to result in a less than proportional increase in plasma concentrations with

increasing dose.

The bracketed approach – where the highest and lowest tablet strengths are studied – is an acceptable

approach for the investigation of bioequivalence where non-linear pharmacokinetics are associated with

a less than proportional increase in AUC and C

over the range of tablet strengths. The Applicant has

also supplied dissolution data that reveal a similarity f

factor higher than 50 over the range of

physiologically relevant pH for the higher tablet strengths.

The supply of two bioequivalence studies at the extremes of the range of proposed tablet strengths is

therefore acceptable to infer bioequivalence across all tablet strengths.

In support of these applications, the applicant submitted the following bioequivalence studies:

STUDY 1

A randomised, open label, two treatment, two period, two sequence, single dose, crossover,

bioequivalence study of the applicant’s test product Prednisolone 2.5mg Tablets (Caduceus Pharma Ltd)

versus the reference product Prednisolon Pfizer 2.5 mg tablets (Pfizer AB, Sweden) in healthy, adult,

subjects under fasting conditions.

Following an overnight fast, subjects were administered a single dose (1 x 2.5 mg tablet) of the test or

the reference product with 240 mL of water.

Blood samples were collected for plasma levels before dosing and up to and including 24 hours after

each administration. The washout period between the treatment phases was 3 days. The pharmacokinetic

results are presented below:

Table: Summary of pharmacokinetic parameters for prednisolone:

area under the plasma concentration-time curve from zero to t hours

0-inf

area under the plasma concentration-time curve from time zero to infinity

maximum plasma concentration

Table: 90% confidence intervals calculated using ln-transformed data:

STUDY 2

A randomised, open label, two treatment, two period, two sequence, single dose, crossover,

bioequivalence study of the applicant’s test product Prednisolone 30mg Tablets (Caduceus Pharma Ltd)

versus the reference product 3 x Prednisolon Pfizer 10 mg tablets (Pfizer AB, Sweden) in healthy, adult,

subjects under fasting conditions.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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Following an overnight fast, subjects were administered a single dose of the test (1 x 30 mg tablet) or the

reference product (3 x 10 mg tablets) with 240 mL of water.

Blood samples were collected for plasma levels before dosing and up to and including 24 hours after

each administration. The washout period between the treatment phases was 3 days. The pharmacokinetic

results are presented below:

Table: Summary of pharmacokinetic parameters for prednisolone:

area under the plasma concentration-time curve from zero to t hours

0-inf

area under the plasma concentration-time curve from time zero to infinity

maximum plasma concentration

Table: Ratio and 90% Confidence Intervals of test product versus Reference Product:

Conclusion

The 90% confidence intervals of the test/reference ratio for AUC and C

values for prednisolone for

the 2.5 mg and 30 mg test product strengths lie within the acceptable limits of 80.00% to 125.00%, in

line with the ‘Guideline on the Investigation of Bioequivalence

(CPMP/EWP/QWP/1401/98 Rev

1/Corr**). Thus, the data support the claim that the applicant’s test products Prednisolone 2.5mg and

30mg Tablets (Caduceus Pharma Ltd) are bioequivalent to the reference products Prednisolon Pfizer 2.5

mg and 10 mg (administered at 3 x 10 mg tablets) [Pfizer AB, Sweden].

As the 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg or 30 mg strength test products meet the biowaiver criteria

specified in the current bioequivalence guidance, the results and conclusions of the bioequivalence

studies with the 2.5 mg and 30 mg tablet strengths can be extrapolated to the 5 mg, 10 mg, 20 mg and 25

mg strength tablets.

IV.3

Pharmacodynamics

No new pharmacodynamic data were submitted and none were required for applications of this type.

IV.4

Clinical efficacy

No new efficacy data were submitted and none were required for applications of this type.

IV.5

Clinical safety

No new safety data were submitted and none are required.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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IV.6

Risk Management Plan (RMP) and Pharmacovigilance System

The marketing authorisation holder (MAH) has submitted a risk management plan (RMP), in accordance

with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities

and interventions designed to identify, characterise, prevent or minimise risks relating to Prednisolone

Tablets.

A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are

listed below:

Summary table of safety concerns:

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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Summary table of risk minimisation measures:

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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IV.7

Discussion on the clinical aspects

With the exception of the bioequivalence studies, no new clinical studies were conducted, which is

acceptable given that the applications were based on being generic/hybrid generic medicinal products of

originator products that have been licensed for over 10 years.

Bioequivalence has been demonstrated between the applicant’s test products Prednisolone 2.5mg and

30mg Tablets (Caduceus Pharma Ltd) and the reference products Prednisolon Pfizer 2.5 mg and 10 mg

(administered at 3 x 10 mg tablets) [Pfizer AB, Sweden].

As the 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg or 30 mg strength test products meet the biowaiver criteria

specified in the current bioequivalence guidance, the results and conclusions of the bioequivalence

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

16

studies with the 2.5 mg and 30 mg tablet strengths can be extrapolated to the 5 mg, 10 mg, 20 mg and 25

mg strength tablets.

The grant of marketing authorisations is recommended for these applications.

V

User consultation

The package leaflet has been evaluated via a user consultation study, in accordance with the

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of

user testing the package leaflet was English.

The results show that the package leaflet meets the criteria for readability, as set out in the

Guideline on

the readability of the label and package leaflet of medicinal products for human use

VI

Overall conclusion, benefit/risk assessment and recommendation

The quality of the products is acceptable, and no new non-clinical or clinical safety concerns have been

identified. Extensive clinical experience with prednisolone is considered to have demonstrated the

therapeutic value of the compound. The benefit-risk is, therefore, considered to be positive.

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) and Patient

Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for this medicine is presented below:

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

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PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

20

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

21

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

22

PAR Prednisolone 2.5mg, 5mg, 10mg, 20mg, 25mg and 30mg Tablets

UK/H/6012/001-006/DC

23

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