Alimemazine 10mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Alimemazine tartrate
Available from:
Advanz Pharma
ATC code:
R06AD01
INN (International Name):
Alimemazine tartrate
Dosage:
10mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 03040100; GTIN: 5060090470201

Vallergan

®

10mg Tablets/

Alimemazine Tartrate 10mg Tablets

(alimemazine tartrate)

Your medicine is known by any of the above names, but will be referred to

as alimemazine tablets throughout this

Patient Information Leaflet

What is in this leaflet:

1) What alimemazine tablets are and what they are used for

2) What you need to know before you take alimemazine tablets

3) How to take alimemazine tablets

4) Possible side effects

5) How to store alimemazine tablets

6) Contents of the pack and other information

1) What alimemazine tablets are and what they are used for

Alimemazine tablets contain the active ingredient alimemazine tartrate and

belongs to a group of medicines called phenothiazines. It works by blocking

a natural substance (histamine) that your body makes during an allergic

reaction. It also works directly on the brain to help you feel more relaxed.

What alimemazine tablets are used for

To treat itching (pruritus) or an itchy, lumpy rash (urticaria)

As a sedative for children aged between 2 and 7 years. This is a

medicine given to reduce awareness or make the child feel relaxed and

at ease before an operation

2) What you need to know before you take alimemazine tablets

Do not take alimemazine tablets if:

You are allergic (hypersensitive) to:

alimemazine tartrate or any of the other ingredients of this medicine

(listed in section 6).

any other similar medicines (phenothiazines) such as

chlorpromazine.

The signs of an allergic reaction include: a rash, swallowing or

breathing problems, swelling of your lips, face, throat or tongue.

You have liver or kidney problems.

You have epilepsy.

You have Parkinson’s disease.

You have thyroid problems (hypothyroidism).

You have a tumour on the adrenal gland (called phaeochromocytoma).

You have myasthenia gravis (a form of muscle weakness).

You have an enlarged prostate gland.

You have increased pressure in the eye (called narrow angle

glaucoma).

You have a history of a blood or bone marrow disorder called

agranulocytosis.

Children

Alimemazine should not be used in children less than 2 years old.

Do not take this medicine if any of the above applies to you.

If you are not sure, talk to your doctor or pharmacist before taking

alimemazine tablets.

Warnings and precautions

Talk to your doctor or pharmacist before taking alimemazine tablets if:

You have heart problems.

You have fits (epilepsy).

You are elderly and are dehydrated or have been told you have a low

blood volume.

You are elderly and have had constipation for some time.

You are an elderly male and have problems when passing water

(urine).

You are elderly and it is very hot or cold. Your body may find it harder to

control its temperature when taking this medicine.

If you are not sure if any of the above apply to you, talk to your doctor or

pharmacist before taking alimemazine tablets.

Other medicines and alimemazine tablets

Tell your doctor or pharmacist if you are taking, have recently taken or

might take any other medicines. This includes medicines you can buy

without prescription, including herbal medicines. This is because

alimemazine tablets can affect the way some medicines work. Also some

medicines can affect the way alimemazine tablets work.

In particular, tell your doctor or pharmacist if you are taking any of the

following:

Medicines to help you sleep or lower your anxiety.

Lithium – used to treat some types of mental illness.

Amphetamine – used for Attention Deficit Hyperactivity Disorder

(ADHD).

Phenobarbital – used for epilepsy.

Adrenaline - used for life threatening allergic reactions.

Medicines for Parkinson’s disease such as levodopa.

Medicines for depression.

Medicines for severe pain (such as codeine or morphine).

Medicines for diabetes. Your doctor may need to change the dose of

your medicine.

Medicines for high blood pressure such as doxazosin, terazosin,

guanethidine or clonidine.

Medicines for indigestion and heartburn (antacids).

Anticholinergic medicines – includes some medicines used for irritable

bowel syndrome, asthma or incontinence.

Alimemazine tablets with alcohol

Do not drink alcohol or take any medicines containing alcohol while you are

taking alimemazine tablets. This is because alcohol can increase the

chances of you getting side effects. It can also cause serious breathing

difficulties.

Pregnancy and breast-feeding

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.

You should not take alimemazine tablets if you are breast-feeding. This is

because small amounts may pass into mothers’ milk. This can be harmful to

your baby.

If you are breast-feeding or planning to breast-feed, talk to your doctor or

pharmacist before taking any medicine.

Driving and using machines

You may feel drowsy or sleepy while taking this medicine. If this happens,

do not drive or use any tools or machines.

Alimemazine tablets contain lactose

If you have been told by your doctor that you cannot tolerate some sugars,

talk to your doctor before taking alimemazine tablets.

3) How to take

alimemazine tablets

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

Check with your doctor or pharmacist if you are not sure.

Taking this medicine

Take this medicine by mouth.

Do not touch the tablets for any longer than is necessary. This can

cause skin redness, swelling and itching (contact skin sensitisation).

If you feel the effect of your medicine is too weak or too strong, do not

change the dose yourself, but ask your doctor.

Do not take more than the recommended dose.

How much to take

The usual dose is:

For itching or an itchy, lumpy rash

Adults:

One tablet (10mg) two or three times each day.

Your doctor may increase your dose in some cases.

Elderly:

One tablet (10mg) once or twice each day.

Children over 2 years of age:

Children will normally be given Alimemazine Tartrate 7.5mg/5ml

Syrup.

You should check with your doctor or pharmacist.

As a sedative

Children aged between 2 and 7 years:

Children will normally be given Alimemazine Tartrate 7.5mg/5ml

Syrup. You should check with your doctor or pharmacist.

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

Assessed against UK PIL

dated January 2018

Final draft mock up

By Ibrahim Karir at

Exposure to sunlight

Alimemazine tablets can make your skin more sensitive to sunlight.

Keep out of direct sunlight while taking this medicine.

If you take more Alimemazine tablets than you should

If you take more alimemazine tablets than you should, tell a doctor or go to

a hospital casualty department straight away. Take the medicine pack with

you. This is so the doctor knows what you have taken. Also do this if a child

under 2 years of age swallows some of this medicine.

The following effects may happen: feeling drowsy, loss of consciousness,

increased or rapid heartbeat, changes in heartbeat, uneven heart beats and

feeling very cold. You may also feel dizzy, light-headed or faint (due to low

blood pressure) and you may notice that you cannot control your

movements (for example of the eyes, neck, arms and legs).

If you forget to take alimemazine tablets

If you forget a dose, take it as soon as you remember it.

However, if it is nearly time for the next dose, skip the missed dose. Do not

take a double dose to make up for a forgotten dose

If you have any further questions on the use of this product, ask your doctor

or pharmacist.

4) Possible side effects

Like all medicines, this medicine can cause side effects, although not

everybody gets them.

Stop taking alimemazine tablets and see a doctor or go to a hospital

straight away if you notice any of the following side effects:

An allergic reaction. The signs may include: a rash, swallowing or

breathing problems, swelling of your lips, face, throat or tongue.

Liver problems that may cause the eyes or skin to go yellow (jaundice).

High temperature, sweating, stiff muscles, fast heartbeat, fast breathing

and feel confused, drowsy or agitated. These could be signs of a

serious side effect called ‘neuroleptic malignant syndrome’.

Very fast, uneven or forceful heartbeat (palpitations). You may also

have breathing problems such as wheezing, shortness of breath,

tightness in the chest and chest pain.

Convulsions/fits and movements that you cannot control, mainly of the

tongue, mouth, jaw, arms and legs.

You may get infections more easily than normal such as fever, severe

chills, sore throat or mouth ulcers. These could be signs of a blood

problem.

Tell a pharmacist or doctor as soon as possible if you have any of the

following side effects:

Breathing more slowly or less deeply than normal.

Feeling restless and not being able to keep still.

Changes in skin or eye colour.

Problems with your eyesight.

Rigid or stiff muscles, trembling or shaking or difficulty moving.

Feeling dizzy, lightheaded or faint when you stand or sit up quickly (due

to low blood pressure).

Unexpected excitement or hyperactivity. Problems passing urine.

Tell your doctor or pharmacist if any of the following side effects gets

serious or lasts longer than a few days or if you notice any side

effects not listed in this leaflet:

Constipation

Dry mouth

Stuffy nose

Difficulty sleeping (insomnia)

Feeling agitated

Dizziness

Headache

Drowsiness

Being more sensitive to the sun than usual

Unusual production of breast milk in men and women

Breast enlargement in men

Loss of menstrual periods

Difficulty in getting or maintaining an erection or in ejaculating

(impotence)

Skin redness, swelling and itching (contact skin sensitisation)

Skin rashes

Reporting of side effects

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

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

effects directly via the Yellow Card Scheme at:

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 alimemazine tablets

Keep out of the sight and reach of children.

Do not use alimemazine tablets after the expiry date which is stated on

the carton and blister label after ‘EXP’. The expiry date refers to the last

day of that month.

Do not store above 25°C.

Protect from light

Do not throw away and 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 alimemazine tablets contain:

The active ingredient is alimemazine tartrate. Each film-coated tablet

contains 10mg alimemazine tartrate.

The other ingredients are: lactose, microcrystalline cellulose, colloidal

anhydrous silica, magnesium stearate, sodium starch glycollate,

hypromellose, macrogol 200, indigo carmine (E132), titanium dioxide

(E171).

What alimemazine tablets look like and contents of the pack

Alimemazine tablets are round, dark blue and biconvex, marked with ‘V 10’

on one face and plain on the other.

They are available in blister packs containing 25 tablets.

PL 10383/2193

Vallergan 10mg Tablets/

Alimemazine Tartrate 10mg Tablets POM

Who makes and repackages your medicine

Your medicine is manufactured by Famar Health Care Services Madrid,

S.A.U., Alcorcon, Madrid, Spain.

Procured from within the EU and repackaged by Product Licence Holder:

Primecrown

Ltd,

Northolt

Trading

Estate,

Belvue

Road,

Northolt,

Middlesex, UB5 5QS.

Leaflet date: 08.01.2019

Vallergan is a registered trademark of SANOFI, France.

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Alimemazine Tartrate 10mg Film Coated Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Alimemazine tartrate 10mg

For the full list of excipients see section 6.1.

3

PHARMACEUTICAL FORM

Circular, film coated biconvex tablet with bevelled edge, dark blue in colour, one face

impressed V/10. The reverse side is plain

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Alimemazine has a central sedative effect comparable to that of chlorpromazine but

largely devoid of the latter’s anti adrenaline action.

In adults and children of 3 years and over:

- Pre-medication before general anaesthesia and before stressful or painful process.

- Second-line treatment of the signs and symptoms of allergic rhinitis, conjunctivitis

and urticaria

- Second-line treatment in symptomatic relief of allergic and pruritic dermatological

disorders

4.2

Posology and method of administration

Posology

Not recommended for children less than 3 years old (see also sections 4.3 and 4.4).

DO NOT exceed the recommended dose (see also section 4.9).

Urticaria and pruritus

Adults: 10 mg (approx. 6.5 ml) two or three times daily; up to 100 mg per day have

been used in intractable cases.

Elderly: Dose should be reduced to 10 mg (approx. 6.5 ml) once or twice daily.

Children over 3 years of age: 2.5 – 5 mg (approx. 1.7 – 3.3 ml) three or four times

daily.

Sedative premedication before general anaesthesia

Children aged 3 – 7 years: The maximum dosage recommended is 2 mg (approx. 1.3

ml) per kg bodyweight 1 – 2 hours before the operation.

Method of administration

For oral administration.

4.3

Contraindications

Alimemazine is contraindicated in patients with:

Known hypersensitivity to phenothiazines or to any of the excipients listed in

section 6.1.

Hepatic or renal dysfunction

Epilepsy

Parkinson’s disease

Hypothyroidism

Phaeochromocytoma

Myasthenia gravis

History of narrow angle glaucoma

History of agranulocytosis

Prostatic hypertrophy.

Alimemazine is contraindicated for use in children less than 3 years of age (see

section 4.4).

4.1

Therapeutic indications

Alimemazine has a central sedative effect comparable to that of

chlorpromazine but largely devoid of the latter’s anti adrenaline action.

In children aged 3-7 years:

Pre-medication sedation before general anaesthesia

Adults and children aged 3 years and over:

Second-line treatment in the symptomatic relief of urticaria and

pruritus.

4.5

Interaction with other medicinal products and other forms of interaction

The sedative effects of phenothiazines may be intensified (additively) by alcohol (see section

4.4), anxiolytics & hypnotics, opiates, barbiturates and other sedatives. There may be

increased antimuscarinic and sedative effects of phenothiazines with tricyclic

antidepressants & MAOI’s (including moclobemide). Respiratory depression may

occur.

The hypotensive effect of most antihypertensive drugs especially alpha-

adrenoreceptor blocking agents may be exaggerated by phenothiazines. The use of

antimuscarinics will increase the risk of antimuscarinic side effects when in

conjunction with antihistamines.

The action of some drugs may be opposed by phenothiazines; these include

amphetamine, levodopa, clonidine, guanethidine and adrenaline.

The mild anticholinergic effect of phenothiazines may be enhanced by other

anticholinergic drugs possibly leading to constipation, heat stroke, etc.

Anticholinergic agents may reduce the antipsychotic effect of phenothiazines.

Some drugs interfere with absorption of phenothiazines: antacids, anti-Parkinson and

lithium. Increases or decreases in the plasma concentrations of a number of drugs,

e.g. propranolol and phenobarbital have been observed but were not of clinical

significance.

High doses of phenothiazines reduce the response to hypoglycaemic agents, the

dosage of which may have to be raised. Adrenaline must not be used in patients

overdosed with phenothiazines.

4.6

Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of alimemazine tartrate in pregnant women, but it

has been widely used for many years without apparent ill consequence. Some

phenothiazines have shown evidence of harmful effects in animals. Alimemazine,

like other drugs, should be avoided in pregnancy unless the physician considers it

essential. Neuroleptics may occasionally prolong labour and at such a time should be

withheld until the cervix is dilated 3 – 4 cm. Possible adverse effects on the neonate

include lethargy or paradoxical hyperexcitability, tremor and low Apgar score.

Breast-feeding

Phenothiazines may be excreted in human milk. Breast-feeding should be

discontinued during treatment with alimemazine tartrate.

4.7

Effects on ability to drive and use machines

Patients should be warned about drowsiness during the early days of treatment, and

advised not to drive or operate machinery.

4.8

Undesirable effects

Gastrointestinal disorders:

Constipation

Dry mouth

Respiratory, thoracic and mediastinal disorders:

Nasal congestion

Respiratory depression is possible in susceptible patients

Psychiatric disorders:

Insomnia

Agitation

Nervous system disorders:

Extrapyramidal effects, such as:

Acute dystonias or dyskinesias, usually transitory are commoner in

children and young adults and usually occur within the first 4 days of

treatment or after dosage increases.

Akathisia characteristically occurs after large doses.

Parkinsonism is commoner in adults and the elderly. It usually

develops after weeks or months of treatment. One or more of the

following may be seen – tremor, rigidity, akinesia or other features of

Parkinsonism (commonly just tremor).

Tardive dyskinesia. If this occurs it is usually, but not necessarily,

after prolonged or high dosage. It can even occur after treatment has

been stopped. Dosage should therefore be kept low whenever possible.

Convulsions have been reported in some patients.

Dizziness

Headache

Drowsiness

Hepatobiliary disorders:

Jaundice, usually transient, occurs in a very small percentage of patients. A

premonitory sign may be a sudden onset of fever after one to three weeks of

treatment followed by the development of jaundice. Neuroleptic jaundice has

the biochemical and other characteristics of obstructive jaundice and is

associated with obstructions of the canaliculi by bile thrombi; the frequent

presence of an accompanying eosinophilia indicates the allergic nature of this

phenomenon. Treatment should be withheld on the development of jaundice.

Renal and urinary disorders:

Retention of urine

Vascular disorders:

Hypotension or pallor may occur in children.

Elderly or volume depleted subjects are particularly susceptible to

postural hypotension (see section 4.4).

Cardiac disorders:

Cardiac arrhythmias including atrial arrhythmia, atrioventricular (A-V) block,

ventricular tachycardia and ventricular fibrillation have been reported during

therapy, possibly related to dosage (see section 4.4). Pre-existing cardiac

disease, old age, hypokalaemia and concurrent tricyclic antidepressants may

predispose.

Investigations:

Electrocardiogram changes, usually benign, including:

QT interval prolongation

U-wave abnormality

T-wave abnormality

ST segment depression

Eye disorders:

Accommodation disorders

Blood and lymphatic system disorders:

Mild leukopenia occurs in up to 30% of patients on prolonged high dosage.

Agranulocytosis may occur rarely; it is not dose related.

The occurrence of unexplained infections or fever requires immediate

haematological investigation.

Skin and subcutaneous tissue disorders:

Contact skin sensitisation is a serious but rare complication in those

frequently handling preparations of phenothiazines. Care must be taken to

avoid contact of the drug with the skin.

Skin rashes of various kinds may also be seen in patients treated with the

drug.

Patients on high dosage may develop photosensitivity in sunny weather

and should avoid exposure to direct sunlight (see section 4.4). Ocular

changes and the development of a metallic greyish-mauve colouration of

exposed skin have been noted in some individuals, mainly females, who

have received chlorpromazine continuously for long periods (four to eight

years).

Endocrine disorders:

Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia,

amenorrhoea, impotence.

Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic

dysfunction and altered consciousness) may occur (see section 4.9).

General disorders and administration site conditions:

Paradoxical excitement has been noted.

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 Yellow Card Scheme at:

www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the

Google Play or Apple App Store.

4.9.

Overdose

Symptoms of phenothiazine overdosage include drowsiness or loss of

consciousness, hypotension, tachycardia, ECG changes, ventricular

arrhythmias and hypothermia. Severe extra-pyramidal dyskinesias may occur.

If the patient is seen sufficiently soon (up to 6 hours) after ingestion of a toxic

dose, gastric lavage may be attempted. Pharmacological induction of emesis

is unlikely to be of any use. Activated charcoal should be given. There is no

specific antidote. Treatment is supportive.

Generalised vasodilatation may result in circulatory collapse; Raising the

patient's legs may suffice, in severe cases, volume expansion by intravenous

fluids may be needed; infusion fluids should be warmed before administration

in order not to aggravate hypothermia.

Positive inotropic agents such as dopamine may be tried if fluid replacement is

insufficient to correct the circulatory collapse. Peripheral vasoconstrictor

agents are not generally recommended; avoid the use of adrenaline.

Ventricular or supraventricular tachy-arrhythmias usually respond to

restoration of normal body temperature and correction of circulatory or

metabolic disturbances. If persistent or life-threatening, appropriate anti-

arrhythmic therapy may be considered. Avoid lidocaine and, as far as possible,

long acting anti-arrhythmic drugs.

Pronounced central nervous system depression requires airway maintenance or,

in extreme circumstances, assisted respiration. Severe dystonic reactions,

usually respond to procyclidine (5-10mg) or orphenadrine (20-40mg)

administered intramuscularly or intravenously. Convulsions should be treated

with intravenous diazepam.

Neuroleptic malignant syndrome (NMS) has been reported in the context of

alimemazine overdose. Symptoms of NMS include a combination of

hyperthermia, muscle rigidity, altered mental status and autonomic instability.

Since this syndrome is potentially fatal, alimemazine must be discontinued

immediately, and intensive clinical monitoring and symptomatic treatment

must be initiated.

Strict adherence to the recommended dose is critical (see also section 4.2).

Neuroleptic malignant syndrome should be treated with cooling. Dantrolene

sodium may be tried.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Alimemazine has a central sedative effect, comparable to that of chlorpromazine, but

largely devoid of the latter's anti-adrenaline action. It has powerful antihistamine and

anti-emetic actions.

5.2

Pharmacokinetic properties

There is little information about blood levels, distribution and excretion in humans.

The rate of metabolism and excretion of phenothiazines decreases in old age.

5.3

Preclinical safety data

Not applicable.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Microcrystalline cellulose

Lactose monohydrate (spray dried)

Silica, colloidal anhydrous

Magnesium stearate

Sodium starch glycollate

Hypromellose

Polyethylene glycol 300

Blue opaspray M-1-4229 (purified water EP, Indigo Carmine, Titanium Dioxide,

Industrial Methylated Spirits 74 OP BP, Hydroxypropyl methylcellulose)

Purified water

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

36 months

6.4

Special precautions for storage

Protect from light. Store below 30

6.5

Nature and contents of container

Securitainer or HDPE bottle containing 50 or 500 tablets

PVDC coated uPVC/Al foil blister pack containing 28 tablets

6.6

Special precautions for disposal

Not applicable

7.

MARKETING AUTHORISATION HOLDER

Zentiva Pharma UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

Trading as:

Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK

8

MARKETING AUTHORISATION NUMBER(S)

PL 17780/0464

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

01 August 2009

10

DATE OF REVISION OF THE TEXT

22/04/2020

Alimemazine tartrate 10mg film-coated tablets

UK/H/4749/001/DC

1

Public Assessment Report

Decentralised Procedure

Alimemazine tartrate 10mg film-coated tablets

Procedure No: UK/H/4749/001/DC

UK Licence No: PL 43659/0015

PRIMEGEN Limited

Alimemazine tartrate 10mg film-coated tablets

UK/H/4749/001/DC

2

LAY SUMMARY

Alimemazine tartrate 10mg film-coated tablets

This is a summary of the Public Assessment Report (PAR) for Alimemazine tartrate 10mg film-coated

tablets (PL 43659/0015, previously PL 41830/0028; UK/H/4749/001/DC). It explains how the

application for Alimemazine tartrate 10mg film-coated tablets was assessed and its authorisation

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

use Alimemazine tartrate 10mg film-coated tablets.

For practical information about using Alimemazine tartrate 10mg film-coated tablets, patients should

read the package leaflet or contact their doctor or pharmacist.

The product may be referred to as ‘Alimemazine tartrate’ in this report.

What is Alimemazine tartrate and what is it used for?

Alimemazine tartrate is a ‘generic medicine’. This means that Alimemazine tartrate is similar to a

‘reference medicine’ already authorised in the UK called Vallergan Tablets 10mg (Winthrop

Pharmaceuticals Ltd), which was authorised on 01 July 1998.

Alimemazine tartrate is used:

to treat itching (pruritus) or an itchy, lumpy rash (urticaria);

as a sedative for children aged between 2 and 7 years. This medicine is given to reduce awareness or

make the child feel relaxed and at ease before an operation. (The use of Alimemazine syrup is

recommended for this indication).

How does Alimemazine tartrate work?

Alimemazine tartrate contains the active ingredient Alimemazine tartrate, which belongs to a group of

medicines called phenothiazines. It works by blocking a natural substance (histamine) that the body

makes during an allergic reaction. It also works directly on the brain to help the patient feel more

relaxed.

How is Alimemazine tartrate used?

Alimemazine tartrate is available as film-coated tablets and should be swallowed. The tablets should not

be touched for longer than is necessary, as this can cause skin redness, swelling and itching (contact skin

sensitisation).

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

route of administration, the duration of treatment and the need for any specific monitoring of certain

parameters or for diagnostic tests.

Alimemazine tartrate can only be obtained with a prescription. The patient should check with the doctor

or pharmacist if she is not sure about what to do.

What benefits of Alimemazine tartrate have been shown in studies?

As Alimemazine tartrate is a generic medicine, studies in patients have been limited to tests to determine

that Alimemazine tartrate is bioequivalent to the reference medicine, Vallergan Tablets 10mg (Winthrop

Pharmaceuticals Ltd). Two medicines are bioequivalent when they produce the same levels of the active

substance in the body.

In addition, the Marketing Authorisation Holder (NRIM Limited) has provided data from the published

Alimemazine tartrate 10mg film-coated tablets

UK/H/4749/001/DC

3

literature on alimemazine tartrate.

What are the possible side effects of Alimemazine tartrate?

Because Alimemazine tartrate is a generic medicine and is bioequivalent to the reference medicine

Vallergan Tablets 10mg (Winthrop Pharmaceuticals Limited), the benefits and possible side effects are

taken as being the same as those of the reference medicine.

For the full list of all side effects reported with Alimemazine tartrate, see section 4 of the package

leaflet.

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

Why is Alimemazine tartrate approved?

It was concluded that, in accordance with EU requirements, Alimemazine tartrate has been shown to

have comparable quality and to be comparable to Vallergan Tablets 10mg (Winthrop Pharmaceuticals

Limited). Therefore, the MHRA decided that, as for Vallergan Tablets 10mg (Winthrop Pharmaceuticals

Limited)), the benefits outweigh the identified risks and recommended that Alimemazine tartrate can be

approved for use.

What measures are being taken to ensure the safe and effective use of Alimemazine tartrate?

A risk management plan has been developed to ensure that Alimemazine tartrate is used as safely as

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

Characteristics and the package leaflet for Alimemazine tartrate, 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 Alimemazine tartrate

Ireland and the UK agreed to grant a Marketing Authorisation for Alimemazine tartrate 10mg

film-coated tablets on 21 November 2014. A Marketing Authorisation (Alimemazine tartrate 10mg

film-coated tablets; PL 41830/0028) was granted in the UK to NRIM Limited on 05 January 2014.

Subsequent to a Change of Ownership procedure, the Marketing Authorisation (Alimemazine tartrate 10

mg film-coated tablets; PL 43659/0015) was granted to PRIMEGEN Limited on 09 February 2015.

The full PAR for Alimemazine tartrate follows this summary.

For more information about treatment with Alimemazine tartrate, read the package leaflet or contact

your doctor or pharmacist.

This summary was last updated in February 2015.

Alimemazine tartrate 10mg film-coated tablets

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SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 5

Quality aspects

Page 6

Non-clinical aspects

Page 10

Clinical aspects

Page 11

User consultation

Page 14

Overall conclusion, benefit/risk assessment and

recommendation

Page 14

Annex 1 - Table of content of the PAR update for MRP and

Page 16

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Scientific discussion

I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, Ireland and the UK considered that the

application for Alimemazine tartrate 10mg film-coated tablets (PL 41830/0028; UK/H/4749/001/DC)

could be approved. This is a prescription-only medicine (POM).

Alimemazine has powerful antihistamine and anti-emetic actions and is used in the management of

urticaria and pruritus.

Alimemazine may be used in pre-medication as a sedative before anaesthesia in children aged between 2

to 7 years. The alimemazine syrup formulation is suitable for these indications in children.

This application was submitted using the Decentralised Procedure (DCP), with the UK as Reference

Member State (RMS), and Ireland as Concerned Member State (CMS). The application for

Alimemazine tartrate 10 mg film-coated tablets was submitted under Article 10(1) of Directive

2001/83/EC, as amended, as a generic application. Alimemazine tartrate 10 mg film-coated tablets cross-

refer to the reference medicinal product Vallergan Tablets 10mg (PL 17780/0464; Winthrop

Pharmaceuticals Limited),which was first authorised in the UK on 01 March 1998.

Alimemazine tartrate 10mg film coated tablets contains the active ingredient alimemazine tartrate.

Alimemazine is a histamine H

receptor antagonist belonging to the antihistamine category.

Alimemazine (previously known as trimeprazine) is a tricyclic antihistamine, similar in structure to the

phenothiazine antipsychotics, but differing in the ring-substitution and chain characteristics.

Alimemazine competes with free histamine for binding to the histamine H

receptor and therefore blocks

histamine-mediated symptoms such as itching. Alimemazine has a central sedative effect comparable to

that of the related drug chlorpromazine but is largely devoid of the latter’s anti-adrenaline action.

Alimemazine also has anti-emetic actions.

One bioequivalence study was submitted to support this application, comparing the applicant’s test

product Alimemazine tartrate 10 mg tablets (NRIM Limited, UK with the reference product Vallergan

10mg tablets under fasting conditions. The bioequivalence study was carried out in accordance with

Good Clinical Practice (GCP).

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

which is acceptable given that the application was based on the product 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 the product.

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

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

standards of GMP are in place at those sites.

The UK and Ireland considered that the application could be approved at the end of procedure (Day 211)

on 21 November 2014. After a subsequent national phase, a licence was granted to NRIM Limited in the

UK on 05 January 2015.

Subsequent to a Change of Ownership procedure, the Marketing Authorisation (Alimemazine tartrate

10mg film-coated tablets; PL 43659/0015) was granted to PRIMEGEN Limited on 09 February 2015.

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II

QUALITY ASPECTS

II.1

Introduction

The submitted documentation concerning the proposed product is of sufficient quality and meets the

current EU regulatory requirements.

The quality overall summary has been written by an appropriately qualified person and is a suitable

summary of the pharmaceutical aspects of the dossier.

Each Alimemazine tartrate 20 mg film-coated tablet contains alimemazine tartrate as 10 mg

alimemazine base. The tablets are dark blue, circular, biconvex and film coated. One side of tablet is

marked with ’AL’ and other side is plain.

The product also contain the pharmaceutical excipients cellulose microcrystalline, lactose monohydrate,

sodium starch glycolate, silica, colloidal anhydrous, magnesium stearate, Hypromellose 2910, Macrogol

400 and Opraspray Blue Liquid M-1-4229. Appropriate justification for the inclusion of each excipient

has been provided.

The finished product is supplied in blisters, in a pack size of 28 film-coated tablets.

Satisfactory specifications and Certificates of Analysis for the primary packaging materials have been

provided. All primary packaging complies with current European regulations concerning materials in

contact with foodstuff.

II.2

DRUG SUBSTANCE – ALIMEMAZINE TARTRATE

INN:

Alimemazine Tartrate

Chemical name:

2RS

N,N,

2-Trimethyl-3-(10

H

-phenothiazin-10-yl)propan-1-amine

hemi[(2

R

R

)-2,3-dihydroxybutanedioate].

Structure:

Molecular formula: C

Molecular weight:

373.5

Appearance:

White or very slightly yellowish powder

Solubility

Freely soluble in water, sparingly soluble in ethanol (96 per cent) and practically

insoluble in toluene

Alimemazine tartrate is the subject of a European Pharmacopoeia monograph.

Synthesis of the active substance from the designated starting materials has been adequately described

and appropriate in-process controls and intermediate specifications are applied. Satisfactory

specification tests are in place for all starting materials and reagents and these are supported by relevant

Certificates of Analysis.

Appropriate proof-of-structure data have been supplied. All potential known impurities have been

identified and characterised.

An appropriate specification is provided for the active substance. Analytical methods have been

appropriately validated and are satisfactory for ensuring compliance with the relevant specifications.

Batch analyses data are provided that comply with the proposed specification.

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

Suitable specifications have been provided for all packaging used. The primary packaging has been

shown to comply with current guidelines concerning contact with foodstuff.

Appropriate stability data have been generated supporting a suitable retest period when stored in the

proposed packaging.

II.3

MEDICINAL PRODUCT

Pharmaceutical Development

The objective of the development programme was to formulate a safe, efficacious, stable, film-coated

tablet bioequivalent to the reference medicinal product Vallergan 10 mg Tablets (Winthrop

Pharmaceuticals Limited, UK). Suitable pharmaceutical development data have been provided for this

application.

Comparative

in-vitro

dissolution profiles have been provided for this product and the reference product.

The dissolution profiles were satisfactory.

All the excipients comply with their respective European Pharmacopoeia monographs, with the

exception of Opraspray Blue Liquid M-1-4229. Opraspray Blue Liquid M-1-4229 is controlled to a

suitable in-house specification.

Satisfactory Certificates of Analysis have been provided for all excipients.

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 conditions as that intended for

human consumption. In addition, the supplier has confirmed that no ruminant material other than calf

rennet is used during the production of lactose monohydrate.

No genetically modified organisms (GMO) have been used in the preparation of these excipients.

Manufacturing Process

A satisfactory batch formula has been provided for the manufacture of the product, along with an

appropriate description of the manufacturing process. Based on pilot- and full-scale batches, the

manufacturing process has been validated and has shown satisfactory results. The Marketing

Authorisation Holder has committed to performing process validation studies on future full-scale

production batches.

Control of Finished Product

The finished product specification is acceptable. Test methods have been described and have been

validated adequately. 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

finished product in the packaging proposed for marketing. Based on the results, a shelf-life 24 months

with thespecial storage conditions ‘Do not store above 30ºC. Store in the original package in order to

protect from light.’ has been accepted.

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

of finished product.

Bioequivalence/Bioavailability

Satisfactory Certificates of Analysis have been provided for the test and reference batches used in the

bioequivalence study. The bioequivalence study is discussed in Section IV, Clinical Aspects.

II.4

Discussion on chemical, pharmaceutical and biological aspects

It is recommended that a Marketing Authorisation is granted for the application for Alimemazine tartrate

10 mg film-coated tablets.

II.5

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

Labels

The SmPC, PIL and labelling are satisfactory and, where appropriate, in line with current guidance.

In accordance with Directive 2010/84/EU, the current version of the SmPC and PIL are available on the

MHRA website. The current labelling is presented below:

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Alimemazine tartrate 10mg film-coated tablets

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III

NON-CLINICAL ASPECTS

III.1

Introduction

The pharmacodynamic, pharmacokinetic and toxicological properties of alimemazine tartrate are well

known. No new non-clinical data have been submitted for this application and none are required.

The applicant has provided an overview based on published literature. The non-clinical overview 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, see Section III.1 Introduction, above.

III.3

Pharmacokinetics

Not applicable, see Section III.1 Introduction, above.

III.4

Toxicology

Not applicable, see Section III.1 Introduction, above.

III.5

Ecotoxicity/Environmental Risk Assessment (ERA)

Suitable justification has been provided for non-submission of an Environmental Risk Assessment. As

the product is intended for generic substitution with a product that is already marketed, no increase in

environmental exposure to alimemazine tartrate is anticipated. Thus, the justification for non-submission

of an Environmental Risk Assessment is accepted.

III.6

Discussion of the non-clinical aspects

It is recommended that a Marketing Authorisation is granted for Alimemazine tartrate 10 mg film-coated

tablets, from a non-clinical point of view.

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IV.

CLINICAL ASPECTS

IV.1

Introduction.

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

bioequivalence study detailed below, no new pharmacodynamic or pharmacokinetic data are provided or

are required for this application.

According to the regulatory requirements CPMP/EWP/QWP/1401/98 NfG on the Investigation of

Bioavailability and Bioequivalence, for an immediate release product claiming to be bioequivalent to the

reference product, a bioequivalence study is required to support the application and the applicant has

conducted one.

With the exception of data from the bioequivalence study detailed below, no new pharmacodynamic or

pharmacokinetic data are provided or are required for this application.

IV.2

Pharmacokinetics

In support of the application, the applicant submitted the following bioequivalence study:

An open label, randomised, two-period, two-sequence, two treatment, single dose, crossover study

to compare the pharmacokinetics of the test product Alimemazine Tartrate 10 mg tablets (film-

coated; NRIM Limited) versus the reference product Vallergan 10mg tablets (film-coated tablets

containing 10 mg alimemazine tartrate; Winthrop Pharmaceuticals Limited) in healthy, male

volunteers under fasting conditions.

The subjects were administered one tablet of either the test or the reference product with 240 ml of

water, after at least a 10-hour overnight fast. Blood samples were collected before and up to and

including 48 hours after each administration. The washout period between the treatment phases was

7 days. The pharmacokinetic results are presented below:

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Results

Note for Guidance on the Investigation of Bioavailabilty and Bioequivalence

(CPMP/EWP/QWP/1401/98) defines the confidence limits as 80.00 to 125.00 % for AUC and C

values. Thus, the data support the claim that the applicant’s test product is bioequivalent to the reference

product Vallergan 10mg tablets film-coated tablets (Winthrop Pharmaceuticals Limited) under fasting

conditions.

IV.3

Pharmacodynamics

The clinical pharmacodynamics properties of alimemazine tartrate are well-known. No new

pharmacodynamic data were submitted and none are required for an application of this type.

IV.4

Clinical Efficacy

The clinical efficacy of alimemazine tartrate is well-known. No new efficacy data are presented or are

required for this type of application.

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IV.5

Clinical Safety

With the exception of the safety data generated during the bioequivalence study, no new safety data

were submitted and none are required for this type of application. No new or unexpected safety issues

arose during the bioequivalence study.

IV.6

Risk Management Plan

The MAH has submitted a risk management plan, 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 Alimemazine tartrate 10 mg film-coated

tablets.

A summary of safety concerns is listed in the table below table:

Summary of safety concerns

Important identified risks

Use in patients with hepatic or renal dysfunction.

Exacerbation of symptoms in patients who suffer from

epilepsy, Parkinson’s disease, hypothyroidism,

phaeochromocytoma, myasthenia gravis, prostatic

hypertrophy.

Hypersensitivity reactions to phenothiazines.

Deterioration in vision in patients with history of narrow

angle glaucoma

Postural hypotension in children and in elderly patients or

volume depleted patients.

Ileus when used in elderly patients with chronic constipation

Tachycardia when used in patients with certain

cardiovascular diseases

Skin sensitisation and photosensitivity reaction upon

exposure to sunlight

Extrapyramidal side effects, especially in children or young

adults.

Leukopaenia and agranulocytosis

Drowsiness which may have an effect on the ability to drive

and operate machinery.

Use in pregnancy and lactation.

Important potential risks

Failure of thermoregulation with hypothermia or

hyperthermia when used in the presence of extremes of

temperature

Increased sedative effect in patients who consume alcohol or

those taking medicines containing alcohol, on anxiolytics,

hypnotics, opiates, barbiturates or other sedatives

Increased sedative effect and risk of respiratory depression

when used in patients on tricyclic antidepressants and

Monoamine Oxidase Inhibitors (MAOIs)

Exaggerated hypotensive effect when used in patients taking

antihypertensive drugs

Increased anticholinergic effects when used in patients

taking anticholinergic drugs.

Reduced efficacy of the following treatments: amphetamine,

levodopa, clonidine, guanethidine or adrenaline.

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Summary of safety concerns

Reduced response to hypoglycaemic agents with

concomitant use

Cardiac arrhythmias in patients taking QT prolonging drugs

or drugs that cause electrolyte imbalance.

Important missing

information

None

The Applicant proposes routine Pharmacovigilance and routine risk minimisation measures for all safety

concerns, which is accepted.

IV.7

Discussion of the clinical aspects

It is recommended that a Marketing Authorisation is granted for Alimemazine tartrate 10 mg film-coated

tablets.

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 pack 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 AND BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

QUALITY

The important quality characteristics of Alimemazine tartrate 10mg film-coated tablets are well-defined

and controlled. The specifications and batch analytical results indicate consistency from batch to batch.

There are no outstanding quality issues that would have a negative impact on the benefit/risk balance.

NON-CLINICAL

No new non-clinical data were submitted and none are required for an application of this type. As the

pharmacokinetics, pharmacodynamics and toxicology of alimemazine tartrate are well-known, no

additional data were required.

EFFICACY

With the exception of the bioequivalence study, no new data were submitted and none are required for

this type of application.

Bioequivalence has been demonstrated between the applicant’s product and the reference product

Vallergan Tablets 10mg (PL 17780/0464; Winthrop Pharmaceuticals Limited), under fasting conditions.

SAFETY

With the exception of the safety data from the bioequivalence study, no new data were submitted and

none are required for this type of application. As the safety profile of alimemazine tartrate is well-

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15

known, no additional data were required. No new or unexpected safety concerns arose from the safety

data from the bioequivalence study.

PRODUCT LITERATURE

The SmPC, PIL and labelling are satisfactory and, where appropriate, in line with current guidance.

BENEFIT/RISK ASSESSMENT

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

identified. Extensive clinical experience with alimemazine tartrate is considered to have demonstrated

the therapeutic value of the compounds. The benefit/risk assessment is therefore considered to be

positive.

RECOMMENDATION

The grant of a Marketing Authorisation is recommended.

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Annex 1 - Table of content of the PAR update for MRP and DCP

Steps Taken After The Initial Procedure With An Influence On The Public Assessment Report

(Type II variations, PSURs, commitments)

Scope

Procedur

e number

Product

Informatio

n affected

Date of

start of the

procedure

Date of end

procedure

Approval

/ non

approval

Assessme

nt report

attached

(version)

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