FLUANXOL 3 mg tablets

Israel - English - Ministry of Health

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Active ingredient:
FLUPENTIXOL AS DIHYDROCHLORIDE
Available from:
LUNDBECK ISRAEL LTD
ATC code:
N05AF01
Pharmaceutical form:
TABLETS
Composition:
FLUPENTIXOL AS DIHYDROCHLORIDE 3 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
LUNDBECK A/S, DENMARK
Therapeutic group:
FLUPENTIXOL
Therapeutic area:
FLUPENTIXOL
Therapeutic indications:
Schizophrenia, mania.
Authorization number:
050 17 25587 00
Authorization date:
2010-07-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Hebrew

17-08-2016

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IL-067-22-3-134 / 133662

IL-626002 (067-02) / 119778

2014-11-28 / 14:17 / MOVB

Do not exceed the recommended dosage.

consult the doctor or pharmacist.

How to take Fluanxol

Swallow with a drink of water. Do not chew the tablets. There is no information

about crushing or splitting of the tablet.

Duration of treatment

As with other antipsychotic medicines it may take a few weeks before you feel any

improvement.

Continue to take the tablets for as long as your doctor recommended.

Even if your medical situation has improved, do not stop taking the medicine

without consulting the doctor or the pharmacist.

If you stop your treatment too soon your symptoms may return.

If you mistakenly took higher dosage

If you think that you or anyone else may have taken too many Fluanxol tablets

contact your doctor or the nearest hospital immediately. Do this even if there are no

signs of discomfort or poisoning. Take the Fluanxol container with you if you go to a

doctor or hospital.

Symptoms of overdose may include:

Drowsiness

Unconsciousness

Convulsions

Low blood pressure, weak pulse, fast heart rate, pallor, restlessness

High or low body temperature

Changes in heart rate including irregular heart beat or slow heart rate has been

seen when Fluanxol has been given in overdose together with medicines known

If you forget to take Fluanxol

If you forget to take a dose, take the next dose at the usual time. Do not take a

double dose to make up for a forgotten tablet

If you stop taking Fluanxol

Do not stop taking Fluanxol even if you begin to feel better, unless you are told to do so

by your doctor.

Do not take medicines in the dark. Check the label and the dose each time you take

a medicine. Wear glasses if you need them.

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

pharmacist.

SIDE EFFCTS

You should contact your doctor or go to the hospital straight away if you

experience any of the following symptoms:

Unusual movements of the mouth and tongue, this may be an early sign of a

condition known as tardive dyskinesia.

High f

if occurring with sweating and rapid pulse (these symptoms may be signs of a rare

condition called neuroleptic malignant syndrome (NMS) which has been reported

Yellowing of the skin and the white in the eyes this may mean that your liver is

persons):

Sleepiness, inability to sit still or remain motionless, involuntary movements,

slow or diminished movements, dry mouth.

Racing heart rate (tachycardia) or beating of the heart, tremor, repetitive movements

or abnormal postures due to sustained muscle contractions, dizziness, headache,

constipation, vomiting, digestive problems or discomfort centered in the upper

abdomen, diarrhoea, urination disorders, increased sweating, itching, muscle pain,

increased appetite, increased weight, fatigue or weakness, Sleeplessness (insomnia),

depression, nervousness, agitation, decreased sexual drive (libido decreased).

Involuntary movements of the face and limbs, parkinsonism, speech disorder,

convulsion, circular movement of the eyes, abdominal pain, nausea, flatulence,

rash, skin reaction due to sensitivity to light, eczema or inflammation of the skin,

muscle rigidity, decreased appetite, low blood pressure, hot flush, abnormal liver

function tests, sexual disturbance, state of confusion.

Low blood platelet count (thrombocytopenia), low white blood platelet count

(neutropenia), reduced white blood cell count (leukopenia), bone marrow

poisoning (agranulocytosis)

Increased level of prolactin in the blood (hyperprolactinaemia)

High blood sugar (hyperglycaemia), abnormal glucose tolerance

Over-sensitivity (hypersensitivity), acute systemic and severe allergic reaction

(anaphylactic reaction)

Development of breasts in men (gynaecomastia), excessive milk production

(galactorrhoea), lack of menstrual periods (amenorrhoea).

As with other medicines that work in a way similar to flupentixol (the active

QT prolongation (slow heart beat and change in the ECG)

Irregular heart beat

Torsades de Pointes - a special kind of irregular heart rate

In rare cases irregular heartbeats (arrhythmias) may have resulted in sudden death.

Blood clots in the veins especially in the legs (symptoms include swelling, pain and

redness in the leg), which may travel through blood vessels to the lungs causing

medical advice immediately.

In elderly people with dementia, a small increase in the number of deaths has

been reported for patients taking antipsychotics compared with those not receiving

antipsychotics.

HOW TO STORE THIS MEDICINE

Avoid poisoning! This medicine, and all other medicines, must be stored in a

safe place out of the reach of children and/or infants, to avoid poisoning.

Do not induce vomiting unless explicitly instructed to do so by a doctor!

Do not

expiry date refers to the last day of that month.

Do not throw away any Medicines via waste water or household waste. Ask your

pharmacist how to throw away medicines you no longer use. These measures will

help to protect the environment.

CONTENT OF THE PACK AND OTHER INFORMATION

The acti

In addition to the active ingredient this medicine also contains:

The other ingredients are:

beta cycllodextrin, lactose monohydrate, maize starch, hydroxypropylcellulose,

microcrystalline cellulose, croscarmellose sodium, talc, vegetable oil hydrogenated,

magnesium stearate

What Flunaxol look like and contents of the packs:

Flunaxol tablets-each tablet is round, biconvex, in a light brown color.

Licence Holder and address:

Manufacturer name and address: H. Lundbeck A/S, Valby, Denmark

Registration number in the national medicine book of the ministry of health:

Patient leaflet in accordance with the pharmacists' regulations (medical

To be marketed on prescription only.

Fluanxol

Film coted tablets

Composition:

Read all of this leaflet carefully before you start using this medicine.

Keep this leaflet, you may need to read it again.

This leaflet contains essential information regarding this medicine. If you have

any further questions, ask your doctor or the pharmacist.

This medicine has been prescribed for the treatment of your illness. Do not pass

it on to others. It may harm them, even if their signs of illness are the same as

yours

The medicine is not recommended for children and adolescents.

pharmacist.

WHAT THIS MEDICINE IS USED FOR

group of medicines known as antipsychotics (also called neuroleptics).

correct certain chemical imbalances in the brain that are causing the symptoms of

your illness.

Fluanxol is used for the treatment of schizophrenia and mania.

Your doctor, however, may prescribe Fluanxol for another purpose. Ask your doctor

if you have any questions about why Fluanxol has been prescribed for you.

Therapeutic group: Antipsychotic medicines - derivatives of thioxanthene

BEFORE YOU USE THIS MEDICINE

Do not use this medicine

If you are hypersensitive (allergic) to the active ingredient or to any of the other

If you have diminished consciousness.

Special warnings that relate to the use of the medicine

Do not use this medicine without consulting a physician before starting treatment

if you:

have diabetes (An adjustment of the antidiabetic therapy may be required)

poisoning with alcohol)

have risk factors for stroke (e.g. smoking, hypertension)

potassium or magnesium in your blood), or have a genetic predisposition for

any of these.

take or used to take other antipsychotic medicines

are more excited or overactive than normal, since this medicine may increase

these feelings

you or someone else in your family has a history of blood clots, as medicines

like these have been associated with formation of blood clots

During long-term treatment with this medicine blood and liver function test should

be performed.

If you are sensitive to any type of food or medicine, inform your doctor before

commencing treatment.

If you take or took lately other medicines including non-prescription drugs and

food-additives, tell the doctor or pharmacist about it. You should inform the doctor

or the pharmacist especially if you take or have recently taken any of the following

medicines:

Tricyclic antidepressant medicines

Medicines used to lower the blood pressure (e.g. Guanethidine and Clonidine)

Barbiturates (sleeping and sedative medicines)

Medicines used to treat epilepsy

Medicines used to treat Parkinson’s disease (e.g. Levodopa)

Metoclopramide (used in the treatment of gastro-intestinal disorders)

Piperazine (used in the treatment of worms infections in the digestive system).

Medicines that cause a disturbed water or salt balance (too little potassium or

magnesium in your blood)

Medicines known to increase the concentration of Fluanxol in your blood

The following medicines should not be taken at the same time as Fluanxol:

Medicines that change the heartbeat: quinidine, amiodarone, sotalol, dofetilide,

erythromycine, terfenadine, astemizole, gatifloxacin, moxifloxacin, cisapride,

lithium.

Other antipsychotic medicines

Flunaxol with food

Flunaxol can be taken with or without food.

Flunaxol with alcohol

not to drink alcohol during treatment with Fluanxol.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you might be pregnant or are planning

to have a baby, ask your doctor for advice before taking this medicine

Pregnancy

If you are pregnant or think you might be pregnant, consult a doctor before taking

the medicine. Fluanxol should not be used during pregnancy unless clearly

necessary.

medicine.

The following symptoms may occur in newborn babies of mothers that have used

Fluanxol in the last trimester (last three months of their pregnancy): shaking,

contact your doctor.

Breast-feeding

If you are breastfeeding, ask your doctor for advice before taking the medicine. You

should not use Fluanxol when breast-feeding, as small amounts of the medicine

can pass into the breast milk.

Fertility

advice.

Driving and using machines

Do not drive or use dangerous machines during the treatment with Fluanxol, since

this medicine may cause drowsiness or dizziness.

Important information about some of the ingredients of the medicine

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

product. Lactose may cause allergic reaction in people sensitive to lactose.

HOW TO USE THIS MEDICINE

Always take Fluanxol exactly as your doctor has told you. You should check with

your doctor or pharmacist if you are not sure.

The dosage and treatment regimen will be determined by the doctor only

The recommended dose is:

Adults

The dose should be adjusted individually for any patient, according to their

medical situation.

Begin with a small dosages and gradually increase until it reaches the optimal

dosage. The graduation in the dosage shoud be as quickly as possible in

accordance with the reaction for the treatment.

In the maintenance treatment Flunaxol can be taken as a single daily dose in the

morning.

higher dosage may be necessary.

Elderly patients

dosage range.

Patients with special risks-Patients with liver complaints normally receive doses in

the lower end of the dosage range.

Physician Prescribing Information- Fluanxol tabs 3 mg

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Fluanxol 3 mg coated tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Fluanxol 3 mg:

Each tablet contains 3 mg flupentixol (as 3.504 mg flupentixol

dihydrochloride)

Excipients with known effect:

Lactose monohydrate

3 mg: Sunset yellow FCF (E110),

For the full list of excipients see section 6.1

3.

PHARMACEUTICAL FORM

Coated tablet

3mg:

Round,slightly biconvex, ochre-, film coated tablet.

4.

CLINICAL PARTICULARS

1.4

Therapeutic indications

Schizophrenia and mania

1.4

Posology and method of administration

Adults

Schizophrenia and

Dosage should be individually adjusted according to the patient's condition. In

general, small doses should be used initially and increased to the optimal effective

level as rapidly as possible based on the therapeutic response. The maintenance

dose can usually be given as a single morning dose.

Initially 3-15 mg/day divided in two or three daily doses, increased, if necessary, to

40 mg/day.

Maintenance dose usually is 5-20 mg/day.

Older patients

Older patients usually should receive dosages in the lower end of the dosage range.

Reduced renal function

Flupentixol can be given in usual doses to patients with reduced renal function.

Reduced liver function

Careful dosing and, if possible, a serum level determination is advisable .

Children

Flupentixol is not recommended for use in children due to lack of clinical experience.

Method of administration

The tablets are swallowed with water.

1.4

Contra-indications

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

6.1.

Circulatory collapse, depressed level of consciousness due to any cause (e.g.

intoxication with alcohol, barbiturates or opiates), coma.

1.1

Special warnings and precautions for use

The possibility of development of neuroleptic malignant syndrome (hyperthermia,

muscle rigidity, fluctuating consciousness, instability of the autonomous nervous

system) exists with any neuroleptic. The risk is possibly greater with the more potent

agents. Patients with pre-existing organic brain syndrome, mental retardation, and

opiate and alcohol abuse are over-represented among fatal cases .

Treatment: Discontinuation of the neuroleptic. Symptomatic treatment and use of

general supportive measures. Dantrolene and bromocriptine may be helpful.

Symptoms may persist for more than a week after oral neuroleptics are discontinued

and somewhat longer when associated with the depot forms of the drug.

Like other neuroleptics flupentixol should be used with caution in patients with

organic brain syndrome, convulsion and advanced hepatic disease.

Not recommended for excitable or overactive patients in doses up to 25 mg/day since

its activating effect may lead to exaggeration of these characteristics. If previously

the patient has been treated with tranquillizers or neuroleptics with sedative effect,

these should be withdrawn gradually.

As described for other psychotropics flupentixol may modify insulin and glucose

responses calling for adjustment of the antidiabetic therapy in diabetic patients.

Patients on long-term therapy, particularly on high doses, should be monitored

carefully and evaluated periodically to decide whether the maintenance dosage can

be lowered.

As with other drugs belonging to the therapeutic class of antipsychotics, flupentixol

may cause QT prolongation. Persistently prolonged QT intervals may increase the

risk of malignant arrhythmias. Therefore, flupentixol should be used with caution in

susceptible individuals (with hypokalemia, hypomagnesia or genetic predisposition)

and in patients with a history of cardiovascular disorders, e.g. QT prolongation,

significant bradycardia (<50 beats per minute), a recent acute myocardial infarction,

uncompensated heart failure, or cardiac arrhythmia. Concomitant treatment with

other antipsychotics should be avoided (see section 4.5(.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic

drugs. Since patients treated with antipsychotics often present with acquired risk

factors for VTE, all possible risk factors for VTE should be identified before and

during treatment with flupentixol and preventive measures undertaken

Older people

Cerebrovascular

An approximately 3-fold increased risk of cerebrovascular adverse events have been

seen in randomised placebo controlled clinical trials in the dementia population with

some atypical antipsychotics. The mechanism for this increased risk is not known. An

increased risk cannot be excluded for other antipsychotics or other patient

populations. Flupentixol should be used with caution in patients with risk factors for

stroke.

Increased Mortality in older people with Dementia

Data from two large observational studies showed that older people with dementia

who are treated with antipsychotics are at a small increased risk of death compared

with those who are not treated. There are insufficient data to give a firm estimate of

the precise magnitude of the risk and the cause of the increased risk is not known.

Flupentixol is not licensed for the treatment of dementia-related behavioural

disturbances.

Excipients

The tablets contain lactose monohydrate. Patients with rare hereditary problems of

galactose intolerance, the Lapp lactase deficiency or glucose-galactose

malabsorption should not receive this medicine.The tablets also contains Sunset

yellow FCF(E110)which may cuase allergic reaction

1.4

Interactions with other medicinal products and other forms of

interactions

Combinations requiring precautions for use

Flupentixol may enhance the sedative effect of alcohol and the effects of barbiturates

and other CNS depressants.

Neuroleptics may increase or reduce the effect of antihypertensive drugs; the

antihypertensive effect of guanethidine and similar acting compounds is reduced.

Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.

Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of each

other .

Flupentixol may reduce the effect of levodopa and the effect of adrenergic drugs.

Concomitant use of metoclopramide and piperazine increases the risk of

extrapyramidal disorder.

Increases in the QT interval related to antipsychotic treatment may be exacerbated

by the co administration of other drugs known to significantly increase the QT

interval. Co-administration of such drugs should be avoided. Relevant classes

include :

Class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide )

Some antipsychotics (e.g. thioridazine )

Some macrolides (e.g. erythromycin)

Some antihistamines (e.g. terfenadine, astemizole)

Some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

The above list is not exhaustive and other individual drugs known to significantly

increase QT interval (e.g. cisapride, lithium) should be avoided.

Drugs known to cause electrolyte disturbances such as thiazidediuretica

(hypokalemia) and drugs known to increase the plasma concentration of flupentixol

should also be used with caution as they may increase the risk of QT prolongation

and malignant arrythmias (see section 4.4.)

1.4

Fertility, pregnancy and lactation

Pregnancy

Flupentixol should not be administered during pregnancy unless the expected benefit

to the patient outweighs the theoretical risk to the foetus.

Neonates exposed to antipsychotics (including flupentixol) during the third trimester

of pregnancy are at risk of adverse reactions including extrapyramidal and/or

withdrawal symptoms that may vary in severity and duration following delivery. There

have been reports of agitation, hypertonia, hypotonia, tremor, somnolence,

respiratory distress, or feeding disorder. Consequently, newborns should be

monitored carefully.

Animal studies have shown reproductive toxicity (see section 5.3)

Breast-feeding

As flupentixol is found in breast milk in low concentrations it is not likely to affect the

infant when therapeutic doses are used. The dose ingested by the infant is less than

0.5% of the weight related maternal daily dose. Breast-feeding can be continued

during flupentixol therapy if considered of clinical importance but observation of the

infant is recommended, particularly in the first 4 weeks after giving birth.

Fertility

In humans, adverse events such as hyperprolactinaemia, galactorrhoea,

amenorrhoea, libido decreased, erectile dysfunction and ejaculation failure have

been reported (see section 4.8). These events may have a negative impact on

female and/or male sexual function and fertility.

If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual

dysfunctions occur, a dose reduction (if possible) or discontinuation should be

considered. The effects are reversible on discontinuation.

In preclinical fertility studies in rats, flupentixol slightly affected the pregnancy rate of

female rats. Effects were seen at doses well in excess of those applied during clinical

use.

1.4

Effects on ability to drive and use machines

Fluanxol is a non-sedating drug in the low-moderate dosage range.

However, patients who are prescribed psychotropic medication may be expected to

have some impairment in general attention and concentration and should be

cautioned about their ability to drive or operate machinery.

4.8 Undesirable effects

Undesirable effects are for the majority dose dependent. The frequency and severity

are most pronounced in the early phase of treatment and decline during continued

treatment .

Extrapyramidal reactions may occur, especially in the early phase of treatment. In

most cases these side effects can be satisfactorily controlled by reduction of dosage

and/or use of antiparkinsonian drugs. The routine prophylactic use of

antiparkinsonian drugs is not recommended. Antiparkinsonian drugs do not alleviate

tardive dyskinesia and may aggravate them. Reduction in dosage or, if possible,

discontinuation of flupentixol therapy is recommended. In persistent akathisia a

benzodiazepine or propranolol may be useful.

Frequencies are taken from the literature and spontaneous reporting. Frequencies

are defined as :

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), or not known (cannot be

estimated from the available data).

Cardiac disorders

Common

Tachycardia, palpitations.

Rare

Electrocardiogram QT

prolonged.

Blood and lymphatic

system disorders

Rare

Thrombocytopenia,

neutropenia,

leukopenia, agranulocytosis

Nervous system disorders

Very common

Somnolence, akathisia,

hyperkinesia, hypokinesia.

Common

Tremor, dystonia, dizziness,

headache.

Uncommon to Rare

Tardive dyskinesia, dyskinesia,

parkinsonism, speech disorder,

convulsion.

Very rare

Neuroleptic malignant

syndrome.

Eye disorders

Common

Accommodation disorder, vision

abnormal.

Uncommon

Oculogyration.

Respiratory, thoracic and

mediastinal disorders

Common

Dyspnoea.

Gastrointestinal disorders

Very common

Dry mouth.

Common

Salivary hypersecretion,

constipation, vomiting,

dyspepsia, diarrhoea.

Uncommon

Abdominal pain, nausea,

flatulence.

Renal and urinary

disorders

Common

Micturition disorder, urinary

retention.

Skin and subcutaneous

tissue disorders

Common

Hyperhidrosis, pruritus

Uncommon

Rash, photosensitivity reaction,

dermatitis.

Musculoskeletal and

connective tissue disorder

Common

Myalgia.

Uncommon

Muscle rigidity.

Endocrine disorders

Rare

Hyperprolactinaemia.

Metabolism and nutrition

disorders

Common

Increased appetite, weight

increased.

Uncommon

Decreased appetite.

Rare

Hyperglycaemia, glucose

tolerance abnormal.

Vascular disorders

Uncommon

Hypotension, hot flush.

Very rare

Venous thromboembolism

General disorders and

administration site

conditions

Common

Asthenia, fatigue.

Immune system disorders

Rare

Hypersensitivity, anaphylactic

reaction.

Hepatobiliary disorders

Uncommon

Liver function test abnormal.

Very rare

Jaundice.

Reproductive system and

breast disorders

Uncommon

Ejaculation failure, erectile

dysfunction.

Rare

Gynaecomastia, galactorrhoea,

amenorrhoea.

Psychiatric disorders

Common

Insomnia, depression,

nervousness, agitation, libido

decreased.

Uncommon

Confusional state.

As with other drugs belonging to the therapeutic class of antipsychotics, rare cases of

QT prolongation, ventricular arrythmias - ventricular fibrillation, ventricular

tachycardia, Torsade de Pointes and sudden unexplained death have been reported

for flupentixol (see section 4.4).

Abrupt discontinuation of flupentixol may be accompanied by withdrawal symptoms.

The most common symptoms are nausea, vomiting, anorexia, diarrhoea,

rhinorrhoea, sweating, myalgias, paraesthesias, insomnia, restlessness, anxiety, and

agitation. Patients may also experience vertigo, alternate feelings of warmth and

coldness, and tremor. Symptoms generally begin within 1 to 4 days of withdrawal and

abate within 7 to 14 days.

1.4

Overdose

Symptoms :

Somnolence, coma, movement disorder, convulsions, shock,

hyperthermia/hypothermia.

The highest orally administered single dose in clinical trials was 80 mg, and up to 320

mg/day has been given.

ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular

arrhythmias have been reported when administered in overdose together with drugs

known to affect the heart.

Treatment :

Treatment is symptomatic and supportive. Gastric lavage should be carried out as

soon as possible after oral ingestion and activated charcoal may be administered.

Measures to support the respiratory and cardiovascular systems should be instituted.

Epinephrine (adrenaline) should not be used as further lowering of blood pressure

may result. Convulsions may be treated with diazepam and extrapyramidal

symptoms with biperiden .

5.

PHARMACOLOGICAL PROPERTIES

4.4

Pharmacodynamic properties

Pharmacotherapeutic group

Neuroleptics (antipsychotics

ATC-code: N 05 AF 01

Mechanism of action

Flupentixol is a neuroleptic of the thioxanthene group.

Flupentixol is a mixture of two geometric isomers, the active flupentixol and trans(E)

flupentixol, approximately in the ratio of 1:1.

The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking

effect but possibly also 5 HT (5-hydroxytryptamine) receptor blockade contributes. In

vitro and in vivo flupentixol has high affinity for both dopamine D1 and D2 receptors

whereas fluphenazine is almost D2 selective in vivo. The atypical antipsychotic,

clozapine, shows – as flupentixol - equiaffinity to D1 and D2 receptors both in vitro

and in vivo.

Flupentixol has high affinity for α1-adrenoceptors and 5 HT2 receptors, although

lower than that of chlorprothixene, high-dose phenothiazines and clozapine, but no

affinity for cholinergic muscarine receptors. It has only slight antihistaminergic

properties and no α2 adrenoceptor blocking activity.

Flupentixol has proven to be a potent neuroleptic in all the behavioural studies for

neuroleptic (dopamine receptor blocking) activity. Correlation is found in the in vivo

test models, the affinity for dopamine D2 binding sites in vitro and the average, daily

oral antipsychotic doses.

Perioral movements in rats are dependent on D1 receptor stimulation or blockade of

the D2 receptor population. The movements can be prevented by flupentixol.

Likewise, the results from investigations in monkeys indicate that oral hyperkinesia is

more related to D1 receptor stimulation and to a less degree to D2 receptor

supersensitivity. This leads to the suggestion that D1 activation is responsible for

similar effects in man, i.e. dyskinesia. Therefore, blockade of D1 receptors should be

advantageous.

Flupentixol prolongs alcohol- and barbiturate-induced sleeping time in mice in only

very high doses indicating a very weak sedative action in clinical use.

Like most other neuroleptics, flupentixol dose-dependently increases the serum

prolactin level.

Clinical efficacy and safety

In clinical use flupentixol has a broad spectrum of activity that varies according to the

dosage .

Flupentixol in low dosages (1-2 mg/day) has antidepressant, anxiolytic and activating

effects.

In moderate dosages (3-25 mg/day) flupentixol is intended for the treatment of acute

and chronic psychoses. In this dosage range flupentixol has practically no unspecific

sedative effect and is not suited for patients with severe psychomotor agitation.

Besides causing a significant reduction or complete elimination of the nuclear

symptoms of schizophrenia such as hallucinations, delusions and thought

disturbances flupentixol also has disinhibiting (antiautistic and activating) and mood-

elevating properties making flupentixol particularly useful in the treatment of

apathetic, withdrawn, depressed and poorly motivated patients.

The antipsychotic effect increases with increasing dosage; in addition some sedation

should be anticipated. Flupentixol has within the whole dosage range a pronounced

anxiolytic effect and even in high-dose treatment the mood elevating and disinhibiting

effects of flupentixol are retained. High dose treatment does not increase the

frequency of extrapyramidal symptoms.

4.4

Pharmacokinetic properties

The following data concerns the active cis(Z)-isomer.

Absorption

Oral administration results in maximum serum levels in about 4-5 hours. Oral

bioavailability is about 40

Distribution

The apparent volume of distribution (Vd)β is about 14.1 l/kg. The plasma protein

binding is about 99

Biotransformation

The metabolism of flupentixol proceeds along three main routes - sulphoxidation,

side chain N-dealkylation and glucuronic acid conjugation. The metabolites are

devoid of psychopharmacological activity. Flupentixol dominates over metabolites in

brain and other tissues.

Elimination

The elimination half-life (T½ β) is about 35 hours and the mean systemic clearance

(Cls) is about 0.29 l/min.

Flupentixol is excreted mainly with faeces, but also to some degree with the urine.

When tritium labelled flupentixol was administered to man the excretion pattern

showed the excretion via faeces to be about 4 times the urinary excretion.

In nursing mothers flupentixol is excreted in small amounts with the breast milk. The

ratio milk conc./serum conc. in women is on an average 1.3.

Linearity

The kinetics is linear. Steady state plasma levels are achieved in about 7 days. The

mean minimum steady state level corresponding to 5 mg flupentixol orally once-a-

day was about 1.7 ng/ml (3.9 nmol/l.)

Older patients

Pharmacokinetic investigations have not been done in older patients. However, for

the related thioxanthene drug, zuclopenthixol, the pharmacokinetic parameters are

widely independent of the age of the patients.

Reduced renal function

Based on the above characteristics for elimination it is reasonable to assume that

reduced kidney function is likely not to have much influence on the serum levels of

parent drug.

Reduced hepatic function

No data available.

Pharmacokinetic / Pharmacodynamic relationship

A minimum (i.e. concentration measured just before administration of a dose) serum

(plasma) concentration of 1-3 ng/ml (2-8 nmol/l) is suggested as a guideline for

maintenance treatment of schizophrenic patients with a low-moderate degree of

illness.

4.4

Preclinical safety data

Acute toxicity

Flupentixol has low acute toxicity.

Chronic toxicity

In chronic toxicity studies there were no findings of concern for the therapeutic use of

flupentixol.

Reproductive toxicity

In fertility studies in rats, flupentixol slightly affected the pregnancy rate of female

rats. Effects were seen at doses well in excess of those applied during clinical use.

Animal reproduction studies in mice, rats and rabbits have not shown evidence of

teratogenic effects. Embryotoxic effects in terms of increased post implantation

loss/increased absorption rates or occasional abortions were seen in rats and rabbits

at doses associated with maternal toxicity.

Carcinogenicity

Flupentixol has no carcinogenic potential.

6.

PHARMACEUTICAL PARTICULARS

4.4

List of excipients

Tablet core:

Betadex,

Lactose monohydrate 30.6 mg,

Maize starch,

Hydroxypropyl cellulose,

Microcrystalline cellulose,

Croscarmellose sodium,

Talc,

Vegetable oil, hydrogenated,

Magnesium stearate.

Coating and colour

Polyvinyl alcohol, partly hydrolyzed,

Macrogol/PEG 3350,

Talc,

Iron oxide yellow (E172),

Iron oxide red (E 172),

Titanium dioxide (E171),

Sunset yellow FCF (E110),

Macrogol/PEG6000

4.4

Incompatibilities

Not applicable.

4.4

Shelf life

3 years.

4.1

Special precautions for storage

Store below 30ºC.

4.4

Nature and contents of container

and 100 in container (Polypropylene or High Density

Polyethylene (HDPE)

The screw cap of HDPE containers is child-resistant

Not all pack sizes may be marketed.

Special precautions for disposal

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

accordance with local requirements.

7.

MARKETING AUTHORISATION HOLDER

H. Lundbeck A/S

Ottiliavej 9

0055

Valby

Denmark.

8.

MARKETING AUTHORISATION NUMBER:

505.20.00050

9.

Lisence Holder

Lundbeck Israel Ltd.

Derech Hashalom

POB 7328

Tel Aviv

Israel

8.6.2014

העדוה העדוה

לע לע

הרמחה הרמחה

(

(

עדימ עדימ

ןולעב )תוחיטב ןולעב )תוחיטב

ל

ל

אפור אפור

ןכדועמ( ןכדועמ(

05.2013

05.2013

ךיראת

_______

08.06.2014

________________

םש

רישכת

תילגנאב

רפסמו

םושירה

___

050

17

25587

00

_

FLUANXOL

-

____

םש

לעב

םושירה

______

LUNDBECK ISRAEL LTD

_____

ספוט

הז

דעוימ

טורפל

תורמחהה

דבלב

תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Fertility, pregnancy

and Lactation

4.6 Pregnancy and

lactation

Pregnancy

Flupentixol should not be

administered during

pregnancy unless the

expected benefit to the

patient outweighs the

theoretical risk to the foetus.

The newborns of mothers

treated with neuroleptics in

late pregnancy, or labour,

may show signs of

intoxication such as

lethargy, tremor and

hyperexcitability and have a

low apgar score.

-reproduction studies have

given evidence of an

increased incidence of foetal

damage or other deleterious

effects on the reproduction

process.

Animal

Breast-feeding

As flupentixol is found in

breast milk in low

concentrations it is not likely

to affect the infant when

therapeutic doses are used.

The dose ingested by the

infant is less than 0.5% of

the weight related maternal

daily dose. Breast-feeding

can be continued during

flupentixol therapy if

considered of clinical

importance but observation

of the infant is

recommended, particularly

4.6

Fertility, pregnancy and lactation

Pregnancy

Flupentixol should not be administered during

pregnancy unless the expected benefit to the

patient outweighs the theoretical risk to the foetus.

Neonates exposed to antipsychotics (including

flupentixol) during the third trimester of

pregnancy are at risk of adverse reactions

including extrapyramidal and/or withdrawal

symptoms that may vary in severity and duration

following delivery. There have been reports of

agitation, hypertonia, hypotonia, tremor,

somnolence, respiratory distress, or feeding

disorder. Consequently, newborns should be

monitored carefully.

- Animal studies have shown reproductive toxicity

(see section 5.3)

Breast-feeding

As flupentixol is found in breast milk in low

concentrations it is not likely to affect the infant

when therapeutic doses are used. The dose

ingested by the infant is less than 0.5% of the

weight related maternal daily dose. Breast-feeding

can be continued during flupentixol therapy if

considered of clinical importance but observation

of the infant is recommended, particularly in the

first 4 weeks after giving birth.

Fertility

In humans, adverse events such as

hyperprolactinaemia, galactorrhoea, amenorrhoea,

libido decreased, erectile dysfunction and

ejaculation failure have been reported (see section

4.8). These events may have a negative impact on

female and/or male sexual function and fertility.

If clinical significant hyperprolactinaemia,

galactorrhoea, amenorrhoea or sexual

in the first 4 weeks after

giving birth.

dysfunctions occur, a dose reduction (if possible)

or discontinuation should be considered. The

effects are reversible on discontinuation.

In preclinical fertility studies in rats,

flupentixol slightly affected the pregnancy rate of

female rats. Effects were seen at doses well in

excess of those applied during clinical use.

ןולעב :ןכרצל תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח ינפל

שומישה

הפורתב

תוירופו הקנה , ןוירה ,ןוירהב תאש תבשוח וא הקינמ וא ןוירהב תא םא ךלש אפורה תא ילאש ,ןוירהב תויהל תננכתמ וא הפורתה תחיקל ינפל תוירופ עיפשמ לוסקנאולפ יכ וחיכוה תויחב םירקחמב תוירופה לע

אפורה םע ץעייתהל שי

תועפות

יאוול םירגובמב

םע

היצנמד

הילע

הלק

רפסמב

ירקמ תוומה

החווד

םילוחב

םיחקולש

תופורת

יטנא תויטוכיספ

האוושהב

ולאכל

םניאש

םילבקמ תופורת

יטנא

.תויטוכיספ ב"צמ

ובש ,ןולעה

נמוסמ תו

תורמחהה

שקובמה תו

לע

עקר

בוהצ

.

םייוניש

םניאש

רדגב

תורמחה

ונמוס

)ןולעב( עבצב

שי .הנוש

ןמסל

קר

ןכות

יתוהמ

אלו

םייוניש םוקימב

.טסקטה

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