Hydroxyzine Bluefish 10 mg Filmdragerad tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

19-10-2018

Produktens egenskaper Produktens egenskaper (SPC)

25-11-2020

Aktiva substanser:
hydroxizinhydroklorid
Tillgänglig från:
Bluefish Pharmaceuticals AB,
ATC-kod:
N05BB01
INN (International namn):
hydroxizinhydroklorid
Dos:
10 mg
Läkemedelsform:
Filmdragerad tablett
Sammansättning:
hydroxizinhydroklorid 10 mg Aktiv substans; laktosmonohydrat Hjälpämne
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 25 tabletter; Blister, 30 tabletter; Blister, 84 tabletter; Blister, 100 tabletter; Blister, 250 tabletter (dosdispensering); Burk, 25 tabletter; Burk, 30 tabletter; Burk, 84 tabletter; Burk, 100 tabletter; Burk, 250 tabletter (dosdispensering)
Bemyndigande status:
Godkänd
Godkännandenummer:
52841
Tillstånd datum:
2016-03-17

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

05-10-2020

Produktens egenskaper Produktens egenskaper - engelska

25-11-2020

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

14-04-2016

Läs hela dokumentet

Package leaflet: Information for the user

Hydroxyzine Bluefish 10 mg film-coated tablets

hydroxyzine hydrochloride

Read all of this leaflet carefully before you start using 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 Hydroxyzine Bluefish is and what it is used for

What you need to know before you use Hydroxyzine Bluefish

How to use Hydroxyzine Bluefish

Possible side effects

How to store Hydroxyzine Bluefish

Contents of the pack and other information

1.

What Hydroxyzine Bluefish is and what it is used for

Hydroxyzine Bluefish reduces certain activities in the brain without being addictive and

blocks histamine, a substance found in body tissues. It is effective against anxiety, itching and

urticaria.

Hydroxyzine Bluefish is used to treat

anxiety in adults

itching (pruritus) associated with hives (urticaria).

For anxiety, the effect is noticeable after about 15 minutes and remains for around 12 hours.

For itching associated with hives, the effect is reached after about 1 hour and remains for at

least 24 hours.

2.

What you need to know before you take Hydroxyzine Bluefish

Do not take Hydroxyzine Bluefish

if you are allergic to hydroxyzine hydrochloride or any of the other ingredients of this

medicine (listed in section 6).

if you are allergic (hypersensitive) to cetirizine, aminophylline, ethylenediamine or

piperazine derivatives (closely related active substances of other medicines).

if you have porphyria (a metabolic disease).

if you are pregnant or breast-feeding (see section “Pregnancy, breast-feeding and

fertility” below).

if your ECG (electrocardiogram) shows a heart rhythm problem called “QT interval

prolongation”.

if you have or had a cardiovascular disease or if your heart rate is very low.

if you have low salt levels in your body (e.g. low level of potassium or of

magnesium).

if you are taking certain medicines for heart rhythm problems or medicines that may

affect the heart rhythm (see “Other medicines and Hydroxyzine Bluefish”).

if anyone in your close family has died suddenly of heart problems.

Warnings and precautions

Talk to your doctor or pharmacist before taking Hydroxyzine Bluefish:

if you have kidney or liver disease or if you are elderly. You might need a lower dose.

if you have an increased risk of getting fits (seizures)

if you have any risk factors for stroke.

if you have an increase in pressure in the eye (glaucoma)

if you have problems to urinate

if you have constipation (slow intestinal function).

if you have a severe muscle weakness (myasthenia gravis).

if you have mental disorders (dementia).

Hydroxyzine Bluefish may be associated with an increased risk of heart rhythm disorder

which may be life threatening. Therefore, tell your doctor if you have any heart problems or

are taking any other medicines, including medicines obtained without prescription.

While taking Hydroxyzine Bluefish, seek immediate medical attention if you experience heart

problems such as palpitations, trouble breathing, loss of consciousness. Treatment with

hydroxyzine should be stopped.

Dry mouth can be a side effect with Hydroxyzine Bluefish use. It is therefore important that

you have good oral hygiene during treatment with Hydroxyzine Bluefish.

undergoing

allergy

testing,

treatment

with

Hydroxyzine

Bluefish

should

discontinued at least 5 days before testing. Ask your doctor for advice.

Caution is required in elderly patients. The duration of the treatment should be as short as

possible.

Other medicines and Hydroxyzine Bluefish

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

medicines. This includes any medicines obtained without prescription. Hydroxyzine Bluefish

can effect or be effected by other medicinal products.

Do not take Hydroxyzine Bluefish if you are taking medicine to treat:

bacterial infections (e.g. antibiotics such as erythromycin, moxifloxacin, levofloxacin).

fungal infections (e.g. pentamidine).

heart problems or high blood pressure (e.g., amiodarone, quinidine, disopyramide, sotalol).

psychoses (e.g. haloperidol).

depression (e.g. citalopram, escitalopram).

gastro-intestinal disorders (e.g. prucalopride).

allergy.

malaria (e.g. mefloquine).

cancer (e.g. toremifene, vandetanib).

drug abuse or severe pain (methadone).

Also, tell your doctor if you are taking:

betahistine used to treat Meniere’s disease (problems with balance and hearing).

medicines used to treat anxiety or help you sleep.

anticholinergic medicines for the treatment of e.g. irritable bowel syndrome (digestive

disorders) and asthma.

cimetidine used for the treatment of stomach problems. This may increase the level of

Hydroxyzine Bluefish in your blood.

monoamine oxidase inhibitors used for the treatment of depression and Parkinson’s

disease.

thiazide diuretics (used to treat e.g. high blood pressure). They may increase the risk for

irregular heart rate.

Hydroxyzine Bluefish with food, drink and alcohol

Taking Hydroxyzine Bluefish at the same time with alcohol should be avoided, because the

combination may enhance the effects of Hydroxyzine Bluefish and thereby the risk of side

effects.

Pregnancy and breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a

baby, ask your doctor or pharmacist for advice before taking this medicine.

Hydroxyzine Bluefish must not be used during pregnancy.

Hydroxyzine, the active substance in Hydroxyzine Bluefish, passes into the foetus. There is a

risk that the foetus may be affected.

Hydroxyzine Bluefish must not be used during breast-feeding.

Hydroxyzine

Bluefish

necessary

during

breast-feeding,

breast-feeding

must

discontinued since hydroxyzine passes into breast milk.

Driving and using machines

Hydroxyzine Bluefish may impair your ability to drive or operate machinery, and may cause

drowsiness, reduce your attention or decrease its ability to react. The appearance of these

effects is more likely at the beginning of treatment or when the dose is increased. Do not

drive or operate machinery if you experience any of these effects.

Hydroxyzine Bluefish contains lactose

Hydroxyzine Bluefish tablets contain lactose. If you have been told by your doctor that you

have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Hydroxyzine film-coated tablets contain sodium

This medicine contains less than 1 mmol sodium (23 mg) per 10 mg tablet, that is to say

essentially ‘sodium-free’.

3.

How to take Hydroxyzine Bluefish

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

doctor or pharmacist if you are not sure.

The dose is decided by the doctor, who adjusts it individually to you.

Hydroxyzine Bluefish should be used at the lowest effective dose and the treatment period

should be as short as possible.

The recommended dose is:

For hives and itching

Adults and adolescents (aged 12 and above):

25-50 mg (1-2 tablets of 25 mg) in the evening. In adults over 40 kg, the maximum daily dose

is 100 mg per day.

Children aged 5-12 years:

10-25 mg (1 tablet of 10 mg or 1 tablet of 25 mg) in the evening.

In children over 40 kg, the maximum daily dose is 100 mg per day.

In children up to 40 kg, the maximum daily dose is 2 mg/kg/day.

If you/your child require a dose below 10 mg or if you/your child have difficulty swallowing

the tablets, other medicinal products containing hydroxyzine may be more appropriate. The

10 mg tablet cannot be divided into two equal doses. Talk to your doctor.

For anxiety

Adults:

10 mg – 50 mg daily (1-5 tablets of 10 mg or 1-2 tablets of 25 mg), divided into 2-3 doses

daily. In adults over 40 kg, the maximum daily dose is 10 tablets of 10 mg or 4 tablets of 25

mg (100 mg per day).

In the treatment of anxiety, drug therapy should only be used to support other forms of

treatment. Do not change the dose without talking to your doctor first.

Elderly patients

In the elderly, it is advised to start with half the recommended dose due to the prolonged

action. The maximum daily dose is 50 mg per day.

Patients with kidney problems

Dosage should be reduced in patients with moderate or severe kidney problems.

Patients with liver problems

In patients with reduced liver activity, it is recommended to reduce the daily dose.

Use in children and adolescents

Hydroxyzine Bluefish is only for the treatment of hives and itching in adolescents and

children aged 5 years and older.

If you take more Hydroxyzine Bluefish than you should

If you have taken too much Hydroxyzine Bluefish, immediately contact your doctor, in

particular if a child has taken too much. In the event of overdose, symptomatic treatment

could be implemented. An ECG monitoring could be undertaken, because of the possibility of

a heart rhythm problem such as QT interval prolongation or Torsade de Pointes.

If you forget to use Hydroxyzine Bluefish

Do not take a double dose to make up for a forgotten tablet.

4.

Possible side effects

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

Stop taking this medicine and seek immediate medical attention if you experience

any problems with the heart rhythm such as palpitations, trouble breathing or loss of

consciousness. (frequency not known, cannot be estimated from the available data)

swelling of face, lips, tongue and/or throat, sometimes with difficulties in breathing or

swallowing (angioedema) (Very rare side effects that may affect up to 1 in 10,000

people)

widespread rashes with blisters (acute generalised exanthematous pustolosis), ring-

shaped, red and often blistering rashes – common on hands and feet (erythema

multiforme), mucosal and skin inflammation in combination with high fever (Stevens-

Johnson syndrome) (Very rare side effects that may affect up to 1 in 10,000 people)

Other side effects that may occur:

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

sleepiness.

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

headache,

drowsiness,

dry mouth,

tiredness.

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

agitation,

confusion,

dizziness,

sleeplessness,

tremors,

feeling sick (nausea),

fever.

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

allergic (hypersensitivity) reactions,

disorientation, hallucinations (seeing things that are not there),

fits (seizures), movement disorder (dyskinesia),

accommodation disturbances of the eye (hard to focus), blurred vision,

low blood pressure,

constipation,

vomiting,

changes in liver enzyme values (transaminase, alkaline phosphate, bilirubin and

glutamyl),

itching, skin rash with redness, spots or blemishes, skin inflammation,

urinary retention

cardiac arrest, effects on the heart rhythm, irregular heart rhythm

Very rare side effects (may affect up to 1 in 10,000 people):

anaphylactic shock (serious allergic reaction),

constrictions in the respiratory passage (bronchospasm),

increased sweating,

Not known (frequency cannot be estimated from the available data):

reduced number of platelets (thrombocytopenia),

aggression,

depression,

recurring involuntary muscle contractions (tics),

abnormal prolonged muscle contractions (dystonia),

sensation of tickling, tingling or numbness (paraesthesia),

fainting

uncontrolled circular movement of the eyes (oculogyration),

diarrhoea,

bedwetting or difficulty urinating (abnormal urinary excretion),

extreme weakness (asthenia),

swelling of tissue due to water retension (oedema),

weight gain.

Reporting of side effects

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

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

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

information on the safety of this medicine.

5.

How to store Hydroxyzine Bluefish

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

Blister:

This medicinal product does not require any special temperature storage conditions.

HDPE bottle:

This medicinal product does not require any special temperature storage conditions.

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

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

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

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 Hydroxyzin Bluefish contains

The active substance is hydroxyzine hydrochloride 10 mg.

The other ingredients are cellulose microcrystalline, lactose monohydrate,

croscarmellose sodium, colloidal anhydrous silica, talc, magnesium stearate,

hypromellose 5cPs, macrogol 400, titanium dioxide (E171)

What Hydroxyzine Bluefish looks like and contents of the pack

White to off-white, round shaped, biconvex, film coated tablets.

Blister:

25, 30, 84, 100 and 250 tablets

Bottle with child resistant cap:

25, 30, 84 and 100 tablets

Bottle with Polypropylene cap:

250 tablets

250 tablets pack are for dose-dispensing.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

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

following names:

Member

state

Proposed (invented) names

Sweden

Hydroxyzine Bluefish

Norway

Hydroxyzine Bluefish

Poland

Hydroxyzinum Adamed

United

Kingdom

Hydroxyzine hydrochloride 10mg Film-coated tablets

France

HYDROXYZINE BLUEFISH 10 mg, .

This leaflet was last revised in 2020-09-11

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SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Hydroxyzine Bluefish 10 mg film-coated tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 10 mg hydroxyzine hydrochloride.

Excipient with known effect:

Each 10 mg film-coated tablet contains 22 mg lactose monohydrate.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablet.

White to off-white, 5.0 mm round shaped, biconvex, film coated tablets.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Symptomatic treatment of anxiety in adults.

Symptomatic treatment of pruritus associated with urticaria.

4.2

Posology and method of administration

Posology

Hydroxyzine Bluefish should be used at the lowest effective dose and for the shortest possible

duration. Do not change dose without first talking to a doctor.

Symptomatic treatment of anxiety:

Adults:

10 mg – 50 mg daily, divided into 2-3 doses daily. In adults over 40 kg, the maximum daily dose is

100 mg per day.

Medicinal treatment of anxiety should always be used as adjuvant therapy. As far as possible,

treatment should be initiated, supervised and discontinued by the same physician.

Symptomatic treatment of pruritus associated with urticaria:

Adults and adolescents (≥12 years):

25-50 mg in the evening. In adults and adolescents over 40 kg, the maximum daily dose is 100 mg per

day.

Children aged 5-12 years:

10-25 mg in the evening

In children over 40 kg, the maximum daily dose is 100 mg per day.

In children up to 40 kg, the maximum daily dose is 2 mg/kg/day.

Since the 10 mg tablet cannot be divided into two equal doses, other appropriate strengths and dosage

forms containing hydroxyzine should be administered in case a dose below 10 mg are required or

higher doses which cannot be divided by 10, eg. 25 mg.

Dose adjustment

Dose should be adjusted within the given dose range in accordance with the treatment response in the

patient.

Special populations

Elderly

In the elderly, it is advised to start with half the recommended dose due to the prolonged action. The

lowest possible dose should be

selected in the treatment of elderly patients. The maximum daily

dose in elderly is 50 mg/day (see section 4.4). The results and need for treatment should be

continuously assessed.

Patients with renal impairment

Dose should be reduced in patients with moderate or severe renal impairment due to decreased

excretion of its metabolite cetirizine.

Patients with hepatic impairment:

Caution is required in patients with hepatic impairment, and a reduction of the dose should be

considered.

4.3

Contraindications

Hypersensitivity to the active substance, to cetirizine, to other piperazine derivatives,

aminophylline, ethylenediamine or any of the excipients listed in section 6.1.

- Patients with porphyria.

- Pregnancy and lactation (see section 4.6).

- Patients with a known acquired or congenital QT interval prolongation.

- Patients with a known risk factor to QT interval prolongation including a known cardiovascular

disease, significant electrolytes imbalance (hypokalaemia, hypomagnesaemia), family history of

sudden cardiac death, significant bradycardia, concomitant use with drugs known to prolong the

QT interval and/or induce Torsade de Pointes (see sections 4.4 and 4.5).

4.4

Special warnings and precautions for use

Cardiovascular effects

Hydroxyzine has been associated with prolongation of the QT interval on the electrocardiogram.

During post-marketing surveillance, there have been cases of QT interval prolongation and torsade

de pointes in patients taking hydroxyzine. Most of these patients had other risk factors, electrolyte

abnormalities and concomitant treatment that may have been contributory (see section 4.8).

Hydroxyzine should be used at the lowest effective dose and for the shortest possible duration.

Treatment with hydroxyzine should be stopped if signs or symptoms occur that may be associated

with cardiac arrhythmia, and the patients should seek immediate medical attention.

Patients should be advised to promptly report any cardiac symptoms.

Patients with hepatic impairment

Dosage should be reduced for patients with hepatic impairment (see section 4.2).

In patients with hepatic impairment who receive hydroxyzine regularly, liver function should be

monitored.

Patients with renal impairment

Hydroxyzine should be used with caution in patients with moderate and severe renal impairment and

the dose should be reduced (see section 4.2).

Elderly patients

Hydroxyzine is not recommended in elderly patients because of a decrease of hydroxyzine elimination

in this population as compared to adults and the greater risk of adverse reactions (e.g. anticholinergic

effects) (see sections 4.2 and 4.8).

In elderly patients, it is recommended to begin treatment with half of the recommended dose due to

prolonged action (see section 4.2).

Because of its potential anticholinergic effects, Hydroxyzine should be used with caution in in

patients suffering from glaucoma, urinary tract obstruction, decreased gastro-intestinal motility,

myasthenia gravis, or dementia.

Hydroxyzine should be administered cautiously in patients with increased risk of convulsions.

Younger children are more susceptible to develop adverse events related to the central nervous system

(see section 4.8). In children, convulsions have been more frequently reported than in adults.

Dosage adjustments may be required if Hydroxyzine is used concomitantly with other central nervous

system depressant drugs or drugs with anticholinergic properties (see section 4.5).

Concomitant use of alcohol and hydroxyzine should be avoided (see section 4.5).

The treatment should be stopped at least 5 days before allergy testing or methacholine bronchial

challenge to avoid effects on the test results (see section 4.5).

Dry mouth may occur with high doses and patients should therefore be informed about this risk and

observe good mouth and tooth hygiene.

The duration of treatment should be agreed on with the patient and the patient should be made aware

of the initial adverse reactions.

An about 3-fold risk of cerebrovascular events has been observed in randomised, placebo-controlled

clinical studies with certain atypical neuroleptics in patients with dementia. Background mechanism

for this increased risk is not known. An increased risk with other neuroleptics and in other patient

populations cannot be excluded. Therefore, hydroxyzine should be used with caution in patients with

risk factors for stroke.

Hydroxyzine film-coated tablets contain lactose (see section 6.1).

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-

galactose malabsorption should not take this medicine.

Hydroxyzine film-coated tablets contain sodium

This medicine contains less than 1 mmol sodium (23 mg) per 10 mg tablet, that is to say essentially

‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

Associations contraindicated:

Co-administration of hydroxyzine with drugs known to prolong the QT interval and/or induce

Torsade de Pointes e.g. class IA (e.g. quinidine, disopyramide) and III antiarrhythmics (e.g.

amiodarone, sotalol), some antihistamines, some antipsychotics (e.g. haloperidol), some

antidepressants (e.g. citalopram, escitalopram), some antimalarial drugs (e.g. mefloquine), some

antibiotics (e.g. erythromycin, levofloxacin, moxifloxacin), some antifungal agents (e.g.

pentamidine), some gastro-intestinal medicines (e.g. prucalopride), some medicines used in cancer

(e.g., toremifene, vandetanib), methadone, increase the risk of cardiac arrhythmia. Therefore, the

combination is contra-indicated (see section 4.3).

Associations not recommended:

Betahistine and anticholinesterase drugs

Hydroxyzine antagonises the effects of betahistine and of anticholinesterases.

Allergy testing

The treatment should be stopped at least 5 days before allergy testing or methacholine bronchial

challenge, to avoid effects on the test results.

MAO-inhibitors

Simultaneous administration of hydroxyzine with monoamine oxidase inhibitors should be avoided.

Associations requiring precaution of use:

Bradycardia and hypokalaemia-inducing drugs

Caution with bradycardia and hypokalaemia-inducing drugs.

CNS depressants

Patients should be informed that hydroxyzine may potentiate the effects of CNS depressants or active

substances having anticholinergic properties. Dose should be adapted on an individual basis.

Alcohol

Alcohol potentiates the effects of hydroxyzine.

Cimetidine

Cimetidine 600 mg twice daily has been shown to increase the serum concentrations of hydroxyzine

by 36% and to decrease peak concentrations of the metabolite cetirizine by 20%.

CYP2D6 substrates

Hydroxyzine is an inhibitor of CYP2D6 (Ki: 3.9 µM: 1.7 µg/ml) and may at high doses cause drug

interactions with CYP2D6 substrates:

beta-blockers (metoprolol, propafenone, timolol)

SSRIs (fluoxetine, fluvoxamine)

antidepressants (amitriptyline, clomipramine, desipramine, duloxetine, imipramine, paroxetine,

venlafaxine)

antipsychotics (aripiprazole, haloperidol, risperidone, thioridazine),

codeine, dextromethorphan, flecainide, mexiletine, ondansetron, tamoxifen, tramadol.

UDP-glucuronyl transferase and cytochrome P450

Hydroxyzine is unlikely to impair the metabolism of drugs which are substrates for cytochrome P450

2C9, 2C19 and 3A4 and UDP-glucuronyl transferases.

CYP3A4/5 inhibitors

Hydroxyzine is metabolised by alcohol dehydrogenase and CYP3A4/5 and an increase in hydroxyzine

blood concentrations may be expected when hydroxyzine is co-administered with active substances

known to be potent inhibitors of these enzymes. Examples of potent inhibitors of CYP3A4/5 are

telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole,

posaconazole and certain HIV protease inhibitors, including atazanavir, indinavir, nelfinavir,

ritonavir, saquinavir, lopinavir/ritonavir, saquinavir/ritonavir, and tipranavir/ritonavir and examples

of potent inhibitors of alcohol dehydrogenase are disulfiram and metronidazole. No interaction with

CYP3A4/5-substrate is expected with hydroxyzine.

Thiazide diuretics

Simultaneous use of active substances that may cause electrolyte disturbances, such as thiazide

diuretics (hypokalaemia), should be avoided as they increase the risk of malignant arrhythmias (see

section 4.4).

4.6

Fertility, pregnancy and lactation

Pregnancy

There is no reliable data on the use of hydroxyzine in pregnant women. Hydroxyzine crosses the

placental barrier leading to higher foetal than maternal concentrations. Animal studies have shown

reproductive toxicity (see section 5.3). Therefore, hydroxyzine is contraindicated during pregnancy.

The following symptoms have been observed, immediately after delivery or a few hours thereafter, in

newborn children to women taking hydroxyzin bluefish during late pregnancy and/or delivery:

hypotension, movement disorders including extrapyramidal symptoms, clonic movements, CNS

depression, neonatal hypoxic conditions or urinary retention.

Breast-feeding

Cetirizine, the main metabolite of hydroxyzine, is excreted in human milk. Although no formal

studies have been conducted concerning the excretion of hydroxyzine in human milk, serious

undesirable effects have been seen in breast-fed newborns/infants of hydroxyzine-treated women.

Therefore, hydroxyzine is contraindicated during breast-feeding. Brest-feeding must be discontinued

if hydroxyzine treatment is necessary.

4.7

Effects on ability to drive and use machines

Hydroxyzine may impair the ability to react and to concentrate. Patients should be warned of this

possibility and cautioned against driving a car or operating machinery. Concomitant use of

Hydroxyzine with alcohol or other sedative drugs should be avoided as it aggravates these effects.

4.8

Undesirable effects

The undesirable effects are mainly associated with CNS depression or paradoxical CNS stimulation,

with anti-cholinergic activity or hypersensitivity reactions.

Clinical trials

Oral administration of hydroxyzine:

The following table lists the undesirable effects reported in placebo-controlled clinical trials at a rate

of at least 1% for hydroxyzine. The trials included 735 patients who received hydroxyzine up to

50 mg daily and 630 patients who received placebo.

Undesirable effect (PT)

undesirable effects for hydroxyzine, undesirable effects for placebo,

Sleepiness

13.74

2.70

Headache

1.63

1.90

Tiredness

1.36

0.63

Dry mouth

1.22

0.63

Post-marketing experience

The table below lists, per system organ class and frequency, the undesirable effects reported during

post-marketing use of the drug.

The frequency has been estimated using the following definitions:

very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1,000 to <1/100);

rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the

available data).

Blood and lymphatic system disorders:

Not known: thrombocytopenia

Immune system disorders:

Rare: hypersensitivity reactions

Very rare: anaphylactic shock

Psychiatric disorders:

Uncommon: agitation, confusion

Rare: disorientation, hallucination

Not known: aggression, depression, tics

Nervous system disorders:

Common: sedation

Uncommon: dizziness, insomnia, tremor

Rare: Seizures, dyskinesia

Not known: dystonia, paraesthesia, syncope

Eye disorders:

Rare: accommodation disorder, blurred vision

Not known: oculogyric crisis

Cardiac disorders:

Rare: cardiac arrest, ventricular fibrillation, ventricular tachycardia

Not known: ventricular arrhythmias (e.g. Torsade de Pointes), QT interval prolongation

(see section 4.4).

Vascular disorders:

Rare: hypotension

Respiratory, thoracic and mediastinal disorders:

Very rare: bronchospasm

Gastrointestinal disorders:

Uncommon: nausea

Rare: constipation, vomiting

Not known: diarrhoea

Hepatobiliary disorders:

Rare: liver function tests abnormal

Not known: hepatitis

Skin and subcutaneous tissue disorders:

Rare: pruritis, erythema, papular rash, urticaria, dermatitis

Very rare: angioedema, increased sweating, fixed drug eruption, acute generalized

exanthematous pustulosis (AGEP), erythema multiforme, Stevens-Johnson syndrome

Not known: Bullous condition e.g. toxic epidermal necrolysis, pemfigoids

Renal and urinary disorders:

Rare: urinary retention

Not known: dysuria, enuresis

General disorders and administration site conditions:

Uncommon: malaise, pyrexia

Not known: asthenia, oedema

Investigations:

Not known: weight gain

Treatment with neuroleptics may cause prolongation of the QT interval and cardiac arrhythmias.

Cases of sudden death which may have cardiac causes (see section 4.4) have been reported during

treatment with these drugs.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare

professionals are asked to report any suspected adverse reactions via the national reporting system

listed in Appendix V.

4.9

Overdose

Toxicity:

60-100 mg hydroxyzine given to a 2yearold child resulted in no or mild intoxication, 300 mg

hydroxyzine given to a 2yearold child resulted in severe intoxication. 1-1.5 g hydroxyzine given to

adults resulted in mild intoxication. 1.5-2.5 g hydroxyzine given to adults resulted in moderate

intoxication.

Symptoms:

Symptoms observed after a major overdose are mainly associated with

strong anticholinergic effects,

CNS depression or CNS paradoxical stimulation. The symptoms include nausea, vomiting,

tachycardia, pyrexia, somnolence, impaired pupillary reflex, tremor, confusion, or hallucination.

These may be followed by depressed level of consciousness, respiratory depression, convulsions or

hypotension. Deepening coma and cardiorespiratory collapse may ensue. Prolonged QT interval and

serious arrhythmia with fatal outcomes have been described in connection with an overdose of

neuroleptics.

Treatment:

Symptomatic and supportive treatment is indicated. Gastric lavage with endotracheal intubation may

be performed if a clinically significant amount of medicine has been ingested. Activated charcoal

should be considered, but there is few data that supports the effect. Airways, respiratory and

circulatory status must be closely monitored with continuous ECG recordings and adequate oxygen

supply must be available. Monitoring of heart rate and blood pressure must be done until the patient is

free of symptoms for 24 hours.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Psycholeptics, anxiolytica, diphenylmethane derivatives, ATC code:

N05BB01

Hydroxyzine hydrochloride is a fast acting H

receptor

antagonist with strongly itch inhibiting and

anti-allergic properties. Effect is reached after about 1 hour and remains for at least 24 hours.

Hydroxyzine hydrochloride also has sedative properties, due to its effect on formatio reticularis. The

effect is noticeable after about 15 minutes and remains for about 12 hours.

Hydroxyzine hydrochloride also has anticholinergic, spasmolytic and adrenolytic action.

Hydroxyzine hydrochloride has a wide therapeutic window and does not cause drug addiction.

5.2

Pharmacokinetic properties

Absorption

Hydroxyzine hydrochloride is rapidly absorbed from the gastrointestinal tract. Maximum plasma

concentration (Cmax) has been shown to occur after around 2 hours (t

) after oral administration.

After single doses of 25 mg and 50 mg in adults, C

is normally 30 respective 70 ng/ml. Rate and

extent of exposure to hydroxyzine hydrochloride are about the same as if given as a tablet or syrup.

After repeated once daily dosing, the concentration increases about 30%. Oral bioavailability of

hydroxyzine hydrochloride compared with intramuscular (IM) administration is about 80%.

Distribution

Hydroxyzine hydrochloride is widely distributed in the body and is generally more concentrated in

tissues than in plasma. The apparent volume of distribution is 7-16 l/kg in adults. Hydroxyzine

hydrochloride is taken up in the skin after oral administration. The hydroxyzine concentrations in the

skin are higher than serum concentrations after both single and multiple dose administration.

Hydroxyzine hydrochloride crosses the placental barrier which may lead to higher foetal than

maternal concentrations.

Biotransformation

Hydroxyzine hydrochloride is extensively metabolized. The formation of the main metabolite

cetirizine, a carboxylic acid metabolite (approximately 45% of the oral dose), is mediated by alcohol

dehydrogenase. This metabolite has significant peripheral H

-antagonistic properties. Other identified

metabolites include an N-dealkylated metabolite, and an O-dealkylated metabolite with a plasma half-

life of 59 hours. These metabolic pathways are mediated primarily by CYP3A4/5.

Elimination

Hydroxyzine’s half-life in adults is about 14 hours (7-20 h). Half-life of the main metabolite cetirizine

in adults is approximately 10 hours. Plasma clearance (CL/F) calculated after an oral dose from

studies, is 13 ml/min/kg. Only 0.8 % of the dose is excreted unchanged in urine after an oral dose.

Cetirizine is mainly excreted unchanged in urine (25 % of oral hydroxyzine hydrochloride dose).

Special populations

Elderly

Hydroxyzine’s pharmacokinetics in elderly was investigated in 9 healthy elderly subjects (69.5 ± 3.7

years) after a single dose of 0.7 mg/kg. Hydroxyzine’s half-life increased to 29 hours and the apparent

volume of distribution volume rose to 22.5 l/kg. Reduction of daily dose is recommended in elderly

patients (see section 4.2).

Paediatric population

Hydroxyzine’s pharmacokinetics was evaluated in 12 children (6.1 ± 4.6 years; 22.0 ± 12.0 kg) after

an oral dose of 0.7 mg/kg. Oral plasma clearance per kg was about 2.5 times higher than in adults.

The half-life was shorter than in adults. It was about 4 hours in 1 year old infants and 11 hours in 14

year old adolescents and increases with age. Dosage should be adjusted to the child (see section 4.2).

Hepatic impairment

In subjects with hepatic impairment secondary to primary biliary cirrhosis, plasma clearance (CL/F)

was approximately 66 % of that in normal subjects. Half-life was increased to 37 hours and serum

concentrations of the carboxylic acid metabolite cetirizine were higher than in young subjects with

normal hepatic function.

Renal impairment

Hydroxyzine’s pharmacokinetics was studied in 8 subjects with severe renal impairment (creatinine

clearance 24 ± 7 ml/min). The exposure (AUC) of hydroxyzine hydrochloride did not change

significantly, while it increased about 5 times for the carboxylic acid metabolite cetirizine. This

metabolite was not removed efficiently by dialysis. To avoid significant accumulation of cetirizine

after repeated dose of hydroxyzine hydrochloride, the daily dose of hydroxyzine hydrochloride should

be reduced in patients with renal impairment (see section 4.2).

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose

toxicity and genotoxicity. No animal carcinogenicity studies have been performed with hydroxyzine.

In rats and rabbits, foetal malformations and foetal abortions were seen with hydroxyzine doses of

50 mg/kg.

In isolated canine Purkinje fibres, hydroxyzine at concentrations of 3 µM increased action potential

duration suggesting that there was an interaction with potassium channels involved with the

repolarisation phase. At higher concentrations, 30 µM, there was a marked decrease in the action

potential duration suggesting a possible interaction with calcium and/or sodium currents.

Hydroxyzine produced inhibition of the potassium (IKr) current in hERG channels expressed in

mammalian cells, with an IC50 of 0.62 µM, a concentration that is between 10 and 60-fold higher

than therapeutic concentrations. However, the hydroxyzine concentrations required to produce effects

on cardiac electrophysiology are 10 to 100-fold higher than those required to block H1 and 5-HT2

receptors. In unrestrained conscious dogs monitored by telemetry, hydroxyzine and its enantiomers

produced similar cardiovascular profiles though there were some minor differences. In the first dog

telemetry study, hydroxyzine (21 mg/kg orally) slightly increased heart rate and shortened PR and QT

intervals. There was no effect on QRS and QTc intervals, and thus at normal therapeutic doses, these

slight changes are unlikely to be of clinical relevance.

Similar effects on heart rate and PR interval were observed in a second dog telemetry study, where the

absence of effects of hydroxyzine on QTc interval was confirmed up to a single oral dose of

36 mg/kg.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Tablet core:

Cellulose microcrystalline

Lactose monohydrate

Croscarmellose sodium

Silica, colloidal anhydrous

Talc

Magnesium stearate

Coating:

Hypromellose 5cPs

Macrogol 400

Titanium dioxide (E171)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

5 Years

6.4

Special precautions for storage

PVC/PVdC- Alu blister:

This medicinal product does not require any special temperature storage conditions.

HDPE bottle:

This medicinal product does not require any special temperature storage conditions.

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

6.5

Nature and contents of container

The 10 mg film-coated tablets are supplied in PVC/PVdC - Alu blisters & HDPE bottles.

PVC/PVdC- Alu blister:

25, 30, 84, 100 and 250 tablets

HDPE bottle with Polypropylene child resistant cap with liner and silica gel desiccant:

25, 30, 84 and 100

HDPE bottle with Polypropylene cap with liner and silica gel desiccant:

250 tablets. This pack is for dose-dispensing.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

7.

MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8.

MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10.

DATE OF REVISION OF THE TEXT

2020-11-25

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